MODULE 1.0

INTRODUCTION TO DISCIPLINES

MODULE OUTLINE

1.1 INTRODUCTION TO GENERAL EPIDEMIOLOGY

1.1.1 Definition, Scope, and Classification

1.1.2 Importance of Epidemiology:

1.1.3 Epidemiologic Methodology:

1.1.4 Historical Evolution of Epidemiologic Knowledge

1.1.5 Ethical Issues in Epidemiology

1.2 INTRODUCTION TO CLINICAL EPIDEMIOLOGY

1.2.1 Definitions, scope, and roles

1.2.2 Historical evolution of clinical medicine

1.2.3 Clinical epidemiology in diagnosis

1.2.4 Clinical epidemiology in treatment and prognosis

1.2.5 Clinical Trials on Humans

1.3 INTRODUCTION TO PUBLIC AND COMMUNITY HEALTH

1.3.1 Definition of Public Health

1.3.2 Disciplines That Assist Public Health

1.3.3 Public Health Programs and Strategies

1.3.4 History of Public Health

1.3.5 Community Health

1.4 INTRODUCTION TO BIOSTATISTICS

1.4.1 Biostatistics as a discipline

1.4.2 History of biostatistics

1.4.3 Limitations of biostatistics

1.4.4 Career opportunities in biostatistics

1.5 INTRODUCTION TO COMPUTING

1.5.1 Information Revolution and Computer Age:

1.5.2 Information System

1.5.3 History of Computing

1.5.4 Computer Hardware Developments:

1.5.5 Computer Software:

UNIT 1.1

INTRODUCTION TO GENERAL EPIDEMIOLOGY

Learning Objectives

· Epidemiology: definition, scope, classification, and importance

· Strengths and weaknesses of the epidemiologic method

· Historical evolution of epidemiology

· Ethical issues in epidemiology

Key-words and terms

· Logic, deductive

· Logic, inductive

· Disease, determinants of disease

· Disease, distribution of disease

· Disease, mechanistic concept of disease

· Disease, non-mechanistic concept of disease

· Epidemiology, qualitative epidemiology

· Epidemiology, descriptive epidemiology

· Epidemiology, analytic epidemiology

· Study, observational study

· Study, experimental study

· Scientific method

· Hypothesis

· Empiricism

· Refutation

· Demographic transition

· Epidemiologic transition

· Hygiene

UNIT SYNOPSIS

1.1.1 DEFINITION, SCOPE, and CLASSIFICATION

Epidemiology is the study of the distribution and determinants of both disease and injury. Two triads are involved in epidemiology: (a) the agent, host, and environment triad and the time, place, and person triad. The primary goals of epidemiology are prevention, control, and, in rare instances, eradication disease and injury. Epidemiology started as a study of epidemics and extended to cover infectious disease and later non-infectious diseases. It has now become a methodological discipline that is used to study disease and non-disease phenomena.

Qualitative epidemiology deals with qualitative descriptions. Quantitative epidemiology deals with numerical descriptions. Observational epidemiology is based on observation of human phenomena. Experimental epidemiology involves assessment of the effects of intervention against a disease phenomenon. Theoretical epidemiology deals with mathematical and methodological issues. Descriptive epidemiology describes the patterns of disease occurrence in terms of place, time and person. Analytic epidemiology seeks to discover the underlying causes of diseases.

Public-health epidemiology deals with preventive medicine. Clinical epidemiology deals with diagnosis, management, and prognosis of disease. Hospital epidemiology deals with nosocomial infections and other aspects of hospital operations that can be studied using epidemiological methodology. Drug or pharmaco-epidemiology studies phenomena of adverse reactions and side-effects of drugs. Genetic epidemiology studies the patterns of inheritance of disease from parents and how genetic and environmental factors interact in the final pathway of disease causation. Molecular epidemiology deals with phenomena at the molecular level. Occupational epidemiology studies diseases due to exposure to hazardous material or working conditions in the work-place. Environmental epidemiology studies the impact of air, water, and soil pollution on health. The supporting disciplines of epidemiology are clinical sciences, demographical sciences, data and information sciences, behavioral sciences, and environmental sciences.

1.1.2 IMPORTANCE and PIONEERS OF EPIDEMIOLOGY

Epidemiology is used in clinical medicine, public health, and actuarial sciences. The major activities of an epidemiologist are: study design including selection of the study sample, data collection, data analysis, data interpretation, and initiation of action programs to prevent disease and promote health. Professional practice and careers in Epidemiology are in government (Ministry of Health), universities, hospitals, and the private sector (drug manufacturers), and research institutes. Famous epidemiologists contributed to the early growth of the discipline. Hippocrates made the first recorded epidemiological observations by describing the relation of disease to climate and geography. John Snow (1813-1858) recognized the importance of field epidemiology in his study of the London cholera and its relation to water pollution William Budd (1811-1880) described the spread of typhoid due to ingestion of infected material from patients. William Furr realized that cycles of epidemics could be described mathematically. Major Greenwood (1880-1949) was chief of epidemiology and vital statistics at the London School of Hygiene and Tropical Medicine worked on models of epidemics.

1.1.3 EPIDEMIOLOGIC METHODOLOGY:

An epidemiologic investigation proceeds through identifying and describing a problem, using the scientific method to formulate and test hypotheses, and interpreting findings. Epidemiological information is sourced from existing data or studies (observational or experimental). Existing data is from census, medical facilities, government, and private sector, health surveys, and vital statistics. Experimental studies, natural or true experiments, involve deliberate human action or intervention whose outcome is then observed. They have the advantage of controlled conditions but have ethical problems of experimenting on humans. Observational studies allow nature to take its course and just record the occurrences of disease and describe the what, where, when, and why of a disease. There are of 3 types of observational studies: cross-sectional, case control, and cohort (follow-up) studies. Their advantage is low cost and fewer ethical issues. They suffer from 3 disadvantages: disease aetiology is not studied directly because the investigator does not manipulate the exposures, unavailability of information, and confounding.

Epidemiological methodology, following the scientific method, is empirical, inductive, and refutative. Epidemiology relies on and respects only empirical findings. Empiricism refers to reliance on physical proof. Induction is building a theory on several individual observations. Refutation is basically refusal of a supposition until it is proved otherwise. Epidemiological investigation is not as deterministic as laboratory investigation but is cheap and easy.

1.1.4 HISTORICAL EVOLUTION OF EPIDEMIOLOGIC KNOWLEDGE

Five stages can be identified in the evolution of epidemiological knowledge. The ancient period up to 1500, the post renaissance period 1500-1750, the sanitary period 1750-1870, the infectious disease period 1870-1945, and modern epidemiology period starting in 1945 (also considered the chronic disease period).

In the ancient period, inter-personal disease transmission, connection between diseases and the environment, quarantine and isolation were known. In 400 BC Hippocrates suggested the relation between disease on one side and lifestyle and environmental factors on the other side.

The post renaissance period witnessed rapid growth of knowledge of pathology, and transmission as well as control of disease. In the 1660s Bacon and others developed inductive logic that provided a philosophical basis for epidemiology. Girolamo Fracastoro (1478-1553) suggested that disease spread by direct contact and by small living particles. In 1683 Van Leeuwenhoek saw microorganisms under the microscope. In 1662 Captain John Graunt analyzed births and deaths and described disease in population quantitatively with significant epidemiological observations and determinations. In 1747 James Lind discovered the prevention of scurvy by conducting one of the first experimental trials on humans. In 1798 Edward Jenner discovered vaccination. Ramazzini wrote on occupational health in 1770. Percival Pott (1713-1788) associated scrotal cancer to chimney soot.

In the sanitary period concern was about environmental correlates of disease; quarantine and isolation were used for disease control.

During the infectious disease period, the microbial basis of disease became firmly established when Louis Pasteur (1822-1895) and Robert Koch (1843-1900) developed the germ theory through experimentation. Dr Robert Koch the father of bacteriology identified causative organisms of anthrax (1876), tuberculosis (1882), and cholera (1883). He developed Koch’s postulates which were criteria for determining an infectious etiology of disease. In 1847 Ignaz Philip Semmelweis suggested hand-washing to avoid obstetric infection. John Snow described the association between cholera and contaminated water by forming and testing a series of hypotheses thus being a pioneer of analytic epidemiology. William Budd in 1857-73 concluded that typhoid was contagious. In 1839 William Farr started the discipline of vital statistics as a system of regular collection and interpretation of data and set up a system for routine summaries of causes of death. Joseph Lister introduced antiseptic surgery in 1865. Manson Barr, Bruce-Chwatt and others studied the transmission of mosquito-borne infections, malaria and yellow fever.

Towards the end of the infectious disease period, there were developments in knowledge of non-infectious disease and statistical methodology. Non-infectious diseases (nutritional, occupational, psychiatric, and environmental) were identified and were studied. In 1905 beriberi was found associated with eating milled rice. In 1920 Joseph Goldberger published a descriptive field study relating pellagra to diets high in cereal & canned foods and free of fresh animal products. Elmer McCollum a Professor at Johns Hopkins since 1918 discovered vitamin-deficiency diseases. Statistical theory and practice developed rapidly towards the close of the 19^th century to keep up with developments in basic research and public health all of which required statistical analysis.

The period of modern epidemiology starting in 1945 is the chronic disease epoch. By 1945 there was convergence of the non-mechanistic concepts of disease (environment, social, and behavioral basis of disease) and the mechanistic concepts of disease (molecular, biological, gent-host interaction). Health was defined in a broad sense as: physical, mental, psychological, and spiritual well-being. Scientists recognized the multi-causal nature of disease (genetic, psycho-social, physiological, and metabolic). The period is witnessed a demographic transition (ageing populations) as an epidemiologic transition (change from communicable to non-communicabe diseases). It also witnessed major studies that helped redefine the direction of epidemiology and public health. In 1949 the Framingham Heart Study was began as the first cohort study of the causative factors of cardiovascular disease. In 1950 Doll and Hill, Levin et al, Schreck et al. and Wynder and Graham published the first case control studies of smoking and lung cancer. In 1954 the Field trials of the Salk polio vaccine were the largest formal human experiment. In 1971-1972 the North Karelia Project and the Stanford Three Community studies were launched as the first community-based cardiovascular disease prevention programs. Further methodological developments were witnessed in this period. In 1960 MacMahon published the first epidemiology textbook with systematic treatment of study design. In 1959 Mantel and Haenszel developed statistical procedures for case control studies. In the 1970s logistic regression and log-linear regression were developed as new multivariate analytic methods. In the 1970s – present new developments in computer hardware and software. In the 1990s molecular techniques are being applied to study of large populations.

1.1.5 ETHICO-LEGAL ISSUES IN EPIDEMIOLOGY

A study involving humans must get approval from a recognized body. For approval the study must fulfill certain criteria. It must be scientifically valid. It is unethical to waste resources (time and money) on a study that will give invalid conclusions. In 1992 the Council for International Organizations of the Medical Sciences published ‘Guidelines for Ethical Review of Epidemiological Studies. Among ethical considerations are: individual vs. community rights, benefits vs. risks, informed consent, privacy and confidentiality, and conflict of interest.

Study interpretation and communication of findings to the public pose problems. Risk reports that are not yet confirmed are picked up by the media and create unnecessary public concern. Study findings affect policy. Epidemiologists must know how to communicate risk to the public. It is an ethical obligation to report research findings to subjects so that they may take measures to lessen risk. Epidemiological evidence is different from legal evidence. Epidemiological evidence may not be accepted in a court of law because it has few certainties; it is concerned with populations whereas legal evidence pertains to individuals.

UNIT OUTLINE

1.1.1 DEFINITION, SCOPE, and CLASSIFICATION

A. Definition

B. Scope of Epidemiology:

C. Classification of Epidemiology

D. Sub-Disciplines of Epidemiology:

E. Supporting Disciplines.

1.1.2 IMPORTANCE OF EPIDEMIOLOGY:

A. Clinical Medicine

B. Public Health:

C. Risk and Actuarial Sciences

D. Epidemiology as a Profession

E. Famous Epidemiologists

1.1.3 EPIDEMIOLOGIC METHODOLOGY:

A. Epidemiological Research

B. Hypotheses:

C. Sources of Epidemiological Data

D. Empiricism, Induction, Refutation, and Bayesianiasm

E. Balance of Strengths and Weaknesses:

1.1.4 HISTORICAL EVOLUTION OF EPIDEMIOLOGIC KNOWLEDGE

A. 1^st Epoch: Ancient Times to 1500 CE

B. 2^nd Epoch: 1500-1750 CE

C. 3^rd Epoch: 1750 - 1870 CE

D. 4^th Epoch: 1870- 1945 CE

E. 5^th Epoch: Period of Modern Epidemiology 1945 - Today

1.1.5 ETHICAL ISSUES IN EPIDEMIOLOGY

A. Ethical Approval

B. Informed Consent

C. Privacy and Confidentiality

D. Conflict Of Interest

E. Study Interpretation and Communication

1.1.1 DEFINITION, SCOPE, and CLASSIFICATION

A. DEFINITION

VARIOUS DEFINITIONS

The word epidemiology is derived from Greek. Epi = among, demo = people, and logos = study. Epidemiology is both a new and an old discipline. Its basic concepts and methodology have been known for centuries. It has however become an organized and recognized independent academic discipline in the past half-century. Epidemiology is both a methodology (for example study design) and substantive information (for example the epidemiology of coronary heart disease). The discipline of epidemiology can be defined in various ways, an indication of its wide scope in public health. It is a basic discipline of both clinical and preventive medicine. Being a methodological discipline it does not have a coherent specific subject matter. It is not a definable body of knowledge. It is a methodology of how to get knowledge. It studies health and disease in a community or a group of individuals rather than an individual. Epidemiological conclusions are based on comparison of groups. It is important to select the groups carefully to avoid bias.

STUDY OF THE DISTRIBUTION and DETERMINANTS OF DISEASE

Epidemiology is the study of the distribution and determinants of disease and injury frequency in human populations. Usually the actual study is carried out in a sample of a study population that is part of the target population. Mere count of disease events without relating them to the underlying population denominators leads to the logical error of the floating numerator. Epidemiologic study focuses on the population at risk. Epidemiologic study of disease distribution includes study of disease occurrence in terms of time, place and persons affected. The affected persons are described in terms of their age, sex, race, socio-economic status, occupation, and culture.

Epidemiologic study of disease determinants includes factors that cause or contribute to disease occurrence. Epidemiology also includes study of the natural history of disease (antecedents & consequences) with view to prevention. Also included is study of all phenomena that are related to disease causation and prevention. Epidemiology can be visualized as 2 types of triads. The first triad is a study of the agent, host, and environment of a disease. The second triad is study of the time, place, and persons involved in disease. The primary goals of epidemiology are prevention, control, and in rare instances eradicate disease and injury.

BASIC ISSUES

Epidemiology deals with the following basic issues about disease: definition, diagnosis, prognosis, measurement, transmission, determinants, natural history, treatment, prevention and control, as well as health care research.

POPULATION-BASED and CLINICAL EPIDEMIOLOGY

Population-based epidemiological study may give an accurate picture that cannot be obtained from study of individual patients in clinics because at the population level false-positive errors balance false negative errors leading to a more accurate result. Epidemiology like politics is the art of the possible. It does not provide conclusive proofs but provides enough information to allow taking preventive action. The purpose of both epidemiology and clinical medicine is to modify the natural history of disease. If left alone, disease will eventually lead to severe complications and death. The primary care physician deals with the causes of disease in the individual. The epidemiologist deals with causes of disease in the population. That is why epidemiology is also called population medicine. Classical epidemiology dealt with infectious disease. Its methodology was extended to chronic diseases over the past 50 years. The epidemiological methodology can be extended to study any event that has a time dimension. An event in this sense is looked at as a change of state.

RANDOM EVENTS

A central axiom of epidemiology is that disease is that disease is a random event in its occurrence but is not randomly distributed in the population. A distinction must be made between random and non-random events. Epidemiology studies random events and cannot be employed for non-random ones. Some man-made events are random because humans do not have a pre-conceived total plan or strategy with anticipation of the outcome. Smoking or driving very fast are man-made events that affect health. They are considered random and can be studied by the epidemiologist. Humans undertake or contribute to such events without prior knowledge or determination of the outcome. There are other man-made events that are not random. A good example is war that is prosecuted with a prior determination of objectives and knowledge of the outcome. Thus war casualties are a major distortion of the usual forces that interact in nature and cannot be studied as an epidemiological phenomenon.

STUDY OF CHANGE

Epidemiology studies phenomena of change that affect disease occurrence. Epidemiologic transition manifests as recurring cycles of epidemics or famines, receding pandemics, change in incidence of degenerative diseases and conditions related to the environment, or the emergence or re-emergence of infectious diseases. The causes of epidemiological transition are changes in the causes of disease, change of age distribution, and change of gender distribution. Demographic transition occurs when the age distribution of a community changes from a predominantly youthful population to one that has a predominance of the elderly with longer life expectancy. Demographic transition is a major factor in epidemiologic transition.

B. SCOPE OF EPIDEMIOLOGY:

FOUR INTER-LINKED STAGES

The scope of epidemiological study has widened and changed with time. It started as a study of epidemics. Then it became study of infectious disease. It was later extended to study of non-infectious diseases. It has now become a methodological discipline that is even beyond study of disease.

STUDY OF EPIDEMICS

Until the mid-19^th century M, epidemiology was only a study of epidemics. Epidemics of infectious disease were frequent and epidemiologists were pre-occupied with them. We now know better and look at epidemics as excessive frequency of disease. The epidemic prevalence of a disease is markedly higher than the non-epidemic prevalence. Epidemics may be acute such as cholera or slow such as lung cancer or coronary heart disease. Thus it is still possible to define epidemiology as a study of epidemics if we consider chronic diseases like coronary heart disease and cancer as slow epidemics. Defining an epidemic requires knowledge of pre-epidemic pattern. It is also important to study the post-epidemic period to determine the end-point of the epidemic so that a decision can be made about stopping preventive intervention.

STUDY OF INFECTIOUS DISEASE STARTING CIRCA 1870

The last quarter of the 19^th century witnessed many new discoveries in the microbiological disease etiology. The microbiological agents, their vectors, and modes of transmission were described. Disease patterns were studied and it was found that disease was not randomly distributed in the population and that there were factors determining the local patterns of distribution. Epidemiology in that era was closely related to microbiology. The book on infectious disease epidemiology is not yet closed. New agents of disease are being discovered. There is change in pathogenesis and transmission of known agents. Changes in human behavior lead to new patterns of disease transmission. New and recent discoveries are uncovering an infectious basis for chronic diseases that were considered non-infectious before.

STUDY OF NON-INFECTIOUS DISEASES STARTING CIRCA 1950 M

Studies in the period after the Second World War showed increasing incidence of chronic diseases due to an older population and relative decrease of infectious disease. Study of these diseases thus became a major pre-occupation of epidemiologists in Europe and America. They studied risk factors, the natural history, and preventive interventions. In this period use of the statistical methodology became more wide-spread. Epidemiology in this period was closely related to study of cancer which is the most serious of the non-communicable diseases. The term chronic is a misnomer because both infectious and non-infectious diseases can be chronic. It is better to talk about communicable and non-communicable diseases.

BEYOND HUMAN DISEASE, STARTING CIRCA 1980 M

Epidemiology has now become a purely methodological tool applied to several disciplines. In the field of health and disease it is applied to communicable and non-communicable diseases. It is used in the fields of health policy & management, health quality assurance, health planning and health evaluation. It is finding increasing application in the social and human sciences.

THE FUTURE OF EPIDEMIOLOGY

Epidemiology will have to contend with new challenges and frontiers: global warming, ozone depletion, environmental pollution, demographic changes, emerging infections, and re-emerging infections. Global warming will lead to increase of disease vectors because of higher ambient temperatures. It will also lead to the melting of the polar ice cap leading to rising sea levels will disrupt coastal ecosystems with yet unknown effects on health. It will affect the weather patterns and agricultural production. The depletion of the ozone layer will allow ultra violet radiation to reach the earth and cause damage to human, animal, and plant DNA. As countries develop industrially, their population structures change. They get more elderly dependent citizens and fewer young workers to support them. Rural to urban migration is creating megacities that have many social problems. New infectious diseases are appearing: HIV, Ebola, Hantavirus, and Lyme disease. Infectious diseases that had been defeated are re-emerging: dengue and tuberculosis. Drug resistance is increasing.

REDEFINITION OF EPIDEMIOLOGY

Epidemiology has expanded so much and has involved itself in so many fields of endeavor that it risks losing its original identity without at the same time picking up a new identity. This may result in its disappearance as a coherent discipline. As a scientific methodological discipline, epidemiology need not be confined to its public health origins. As a methodological discipline it can find applications in the clinical as well as health policy fields. The divorce of epidemiology from public health should be blamed on modern public health practitioners who have moved the field from the narrow confines of scientific investigations to social and policy issues that are more political than scientific. The pressure to be politically correct has also forced epidemiologists to present and interpret their evidence in ways that are considered appropriate. They have had to do this in order to have the audience of the public and the policy makers.

Another force pulling epidemiology from its scientific base lies in its very nature. Over the decades we have been able to decrease the risk of disease by preventive measures before we understood the causal chain in full. This was true of Snow’s work on cholera in London in the 19^th century as it is true of falling lung caner rates due to decrease of smoking. The argument is that the epidemiologist should be more involved in the field with social and other interventions against disease rather than spend time doing careful but slow-yielding studies to understand causal mechanisms. However the involvement of the epidemiologist in social intervention may blind him to basic scientific research. For example some forms of intervention against disease may be acceptable to social stakeholders on economic, social, ethical, or other considerations. The epidemiologist may as a consequence be less inclined to purse research in that direction.

The possibility of dividing the discipline into basic epidemiology emphasizing causal research and applied epidemiology emphasizing intervention against disease in the field can be considered but would be difficult to realize in practice. Epidemiology is so inherently practical in its orientation that it would be difficult if not impossible to confine it to intramural pursuit of causal chains and mechanisms.

The emerging field of molecular epidemiology may resolve many of the dilemmas discussed above. Epidemiology can continue investigating causes of disease in the population using very accurate molecular techniques. It can also be involved in an effective way in disease prevention by using molecular techniques to characterize individual risk profiles so that interventions become more specific for each person.

The availability of a lot of data online is posing a new challenge to epidemiology. In the past epidemiologists used to spend a lot of time thinking about the research they intended to do and developing conceptual approaches and hypotheses before they started collecting data. Such serious thought was needed because data collection was not easy. With readily available data epidemiologists may hasten to analyses that will prove difficult to interpret because of inadequate conceptual thought and planning.

Exponential growth in the quantity and sophistication of statistical techniques also poses a novel challenge to traditional epidemiology. System analysis and meta-analysis are powerful tools that enable deeper understanding of phenomena but which may lead to loss of sight of the simplicity of epidemiology. Traditionally epidemiology never sought understanding all factors involved in disease causation in order to initiate prevention. It has always sought for one or two simple risk factors against which to intervene to break the causal chain. It has been a pride of epidemiologists that they can solve problems that they do not fully understand.

C. CLASSIFICATION OF EPIDEMIOLOGY

ON BASIS OF TYPE OF DATA:

Qualitative epidemiology describes the disease patterns as attributes without quantification. Quantitative epidemiology uses exact numerical data. There was relatively slow development of the epidemiological methodology when the discipline was qualitative. This changed rapidly when epidemiology became quantitative and started being treated as a serious science.

ON THE BASIS OF DATA SOURCE:

Epidemiological data can be obtained by observation of human phenomena (observational epidemiology) or by experimental intervention (experimental epidemiology). Observational epidemiology can be descriptive or analytic. Descriptive epidemiology describes the burden of disease and associated characteristics. It is the extension of demography into medicine. Analytic epidemiology studies causal relations between exposures and disease.

Experimental epidemiology involves intervention against a disease phenomenon and assessment of the effects of the intervention. It is in essence analytical.

ON THE BASIS OF APPLICATION:

We can talk of theoretical (basic) epidemiology and applied epidemiology. Those involved in theoretical epidemiology consider themselves the elite of the discipline who do not dirty their hands with data. They tend to work on the mathematical and philosophical aspects of the discipline which with time find application in the field. Epidemiological knowledge can be applied in various settings such as hospital epidemiology, clinical epidemiology, disease screening epidemiology, drug epidemiology, radiation epidemiology, genetic epidemiology, nutritional epidemiology, environmental epidemiology, occupational epidemiology, geriatric epidemiology, and public health epidemiology.

D. SUB-DISCIPLINES OF EPIDEMIOLOGY:

Epidemiological knowledge has grown so extensively in the past decade that specialization has become necessary thus giving rise to sub-disciplines of epidemiology. Theoretical epidemiology deals with the mathematical and statistical methodology used in data analysis and data interpretation. Descriptive epidemiology describes the patterns of disease occurrence in terms of place, time and person. Analytic epidemiology seeks to discover the underlying causes of diseases. Public-health epidemiology is a general term for the study of public health and preventive medicine which includes risk factors, outcome, treatment, and prevention of disease. Clinical epidemiology is concerned with the diagnosis and management of disease as well as assessing its prognosis. It can alternately be called clinical decision making. Hospital epidemiology deals with nosocomial infections and other aspects of hospital operations that can be studied using epidemiological methodology. Drug or pharmaco-epidemiology studies phenomena of adverse reactions and side-effects of drugs. Genetic epidemiology studies the patterns of inheritance of disease from the parents and how genetic and environmental factors interact in the final pathway of disease causation. Molecular epidemiology will revolutionize all our understanding of diseases, their causation, classification, and treatment. Occupational epidemiology studies diseases due to exposure to hazardous material or working conditions in the work-place. Environmental epidemiology studies the impact of air, water, and soil pollution on health.

E. SUPPORTING DISCIPLINES.

CLINICAL SCIENCES

The following disciplines assist in disease characterization: clinical medicine, pathology, and laboratory medicine. Clinical medicine involves description of symptoms and signs which taken together with diagnostic tests and response to treatment helps in case definition, a basic requirement in epidemiological studies.

DEMOGRAPHICAL SCIENCES

Demography is the study of the population in the aggregate and factors of change in the population. Demographic data provides the denominators needed to compute many epidemiological parameters such as rates, ratios, and proportions.

DATA and INFORMATION SCIENCES

Biostatistics and computer science are employed in data collection, management, and analysis. Developments in computer hardware and software have put enormous data handling and data analysis capabilities at the disposal of the epidemiologist.

BEHAVIORAL SCIENCES

Social and human sciences such as sociology, anthropology, demography, economics, and managerial sciences, help understand human behavior as it relates to disease occurrence and disease prevention.

ENVIRONMENTAL SCIENCES

Physical sciences such as physics, chemistry, geological, and atmospheric sciences provide data on causes of disease in the physical environment.

1.1.2 IMPORTANCE OF EPIDEMIOLOGY:

A. CLINICAL MEDICINE:

Epidemiology is important for the clinician. Epidemiological knowledge is indispensable to the clinician in making decisions about diagnoses, treatment, and prognosis. The clinician requires background clinical epidemiological information about a disease such as incidence rates, sex and age distribution, prevalence, and average duration. This information points to the likely diagnosis while at the same excluding unlikely diagnoses. Epidemiological data and summary statistics help describe the various clinical presentation of a disease which helps the physician in reaching a clinical diagnosis. Epidemiological data also helps the identification of disease syndromes by analyzing and summarizing symptoms and signs. Clinical epidemiological data is used in etiological research by use of case control and cohort study designs. Epidemiological concepts and techniques are used in clinical decision analysis and form the basis for evidence-based medicine. It also helps in the estimation of prognosis.

B. PUBLIC HEALTH:

Epidemiology is the cornerstone of public health. Epidemiological knowledge is indispensable to the public health professional. It contributed in the past to the eradication and control of epidemic diseases and has continued to contribute to prevention of chronic non-communicable diseases. Examples of achievements of epidemiology in public health are (a) control of infectious disease control like cholera, small pox, and childhood infections by mass immunization (b) control of non-infectious disease like lung cancer (c) effective screening for breast cancer and cervical cancer, and (e) successful intervention like the Framingham Heart Study. In many cases epidemiological findings point the way for clinical and laboratory research. This saves money and effort. It is a unique feature of the epidemiological methodology that effective preventive measures can be taken even before specific causes are discovered. Cholera is a classic example of a disease against which effective preventive measures were taken half a century before the discovery of the causative organism. The specific uses of epidemiology in public health are description of the spectrum of disease, description of the natural history of disease, identification of risk factors of disease, prediction of disease trends, and elucidation of the mechanisms of disease transmission.

Epidemiology is necessary in the planning and evaluation of health services. Epidemiological data and tools can be used to assess efficacy, effectiveness, and efficiency of health services. Epidemiological data is needed for community diagnosis (general description of the health status of a community and identification of existing or potential health problems). It is used for needs assessment (identification of the health needs of the community). It is needed for evaluation of public health intervention programs. It also contributes to evaluation of disease trends by comparing disease rates over different time periods. Epidemiologic findings are directly applicable to public health policy formulation.

C. RISK and ACTUARIAL SCIENCES

Epidemiological data and tools are used in the evaluation of individual or community disease risk. The individual benefits by knowing his or her risk profile as related to lifestyle and may decide to make changes. Insurance companies use epidemiological data to estimate individual risk according to their specific risk profile as a basis for computing the premium. Pension schemes use epidemiological data on mortality and morbidity in estimating future pensions and annunities. Risk assessment uses epidemiological data to evaluate specific risks of given environmental exposures.

D. EPIDEMIOLOGY AS A PROFESSION

The major activities of an epidemiologist are: study design including selection of the study sample, data collection, data analysis, data interpretation, and initiation of action programs to prevent disease and promote health. Research and Training in Epidemiology is usually at a post-graduate level with award of four main degrees: Master of Public Health (MPH) and Doctor of Public Health (DrPH) for candidates with medical, nursing, dental, and veterinary backgrounds. The degrees of Master of Science (MSc) and Doctor of Science (D.Sc) are awarded to candidates from science disciplines like biology, zoology etc. The professional practice and careers in Epidemiology are in government and the private sector. In the public sector, epidemiologists work in public health divisions of the Ministry of Health, universities, hospitals, and research institutes. In the private sector epidemiologists work for drug manufacturers.

E. FAMOUS EPIDEMIOLOGISTS

Hippocrates made the first recorded epidemiological observations. In his ‘Airs, Waters, and Places’ he described the relation of disease to climate and geography. In ‘Epidemics 1’ and ‘Epidemics 2’ he described 42 clinical case histories. Hippocrates made very detailed observations but he did not use numerical methods. Had he quantified his observations he would have qualified to get the title of the father of epidemiology.

Galen introduced a theory of disease based on constitutions, humors, and temperaments. The theory survived for several centuries being blindly copied without verification. The theory contributed to delay in development of the discipline of epidemiology because it was false. It however proved useful in explaining some phenomena for example Thomas Syndenham (1624-1689 CE) used the theory of constitutions to explain the recurrent epidemics of plague.

John Snow (1813-1858) recognized the importance of field epidemiology in his study of the London cholera. Asian cholera had reached the UK in 1831. It caused outbreaks in 1831-2, 1848-49, 1853-54, 1868, and 1893. The Broad Street Pump cholera incident occurred towards the close of 18554. Over 500 cholera cases deaths were recorded in 10 days in a small area of central London. Deaths ceased following Snow’s advice to remove the pump handle. Snow concluded from his epidemiological studies that cholera was due to ingestion of fecal material. He suggested purification of contaminated water by sand filtration or allowing water to settle in reservoirs.

William Budd (1811-1880) described the spread of typhoid due to ingestion of infected material from patients. William Furr realized that cycles of epidemics could be described mathematically and contributed a lot to vital statistics. Major Greenwood (1880-1949) was chief of epidemiology and vital statistics at the London School of Hygiene and Tropical Medicine and worked on models of epidemics.

1.1.3 EPIDEMIOLOGIC METHODOLOGY:

A. EPIDEMIOLOGICAL RESEARCH

PURPOSES OF RESEARCH

The main purposes of epidemiological research can be listed as exploration, description, explanation, and prediction. Exploratory studies are preliminary and have the objective of obtaining basic information about a disease and its potential causes in order to enable formulation of causal hypotheses that can be tested in more sophisticated studies. Descriptive studies characterize a disease in terms of place, time, and person. Explanatory studies seek to establish causal relations between a disease and its risk factors. Prediction uses existing epidemiological profiles of a disease and its exposures to predict future disease patterns.

STEPS OF AN EPIDEMIOLOGIC INVESTIGATION

An epidemiological investigation proceeds in several stages. A decision has to be made that a public health or medical problem exists. This is followed by description of the extent and distribution of the problem. Hypotheses are then formulated about the causes of the problem. Appropriate studies are designed to test the hypotheses. An epidemiologic study involves data collection, data analysis, and data interpretation. Biostatistics is the technology of the scientific method that enables sophisticated data analysis and interpretation.

B. HYPOTHESES:

Epidemiology, as a scientific discipline, uses the procedures of the scientific method. The procedures require stating a hypothesis, collecting and analyzing data to test the hypothesis, and reaching conclusions about the hypothesis. Continuous improvement of knowledge is by generating and testing hypotheses. The hypothesis is based on previous knowledge or data. It may also be based on purely theoretical or intuitive considerations. An epidemiological hypothesis is formulated to relate two phenomena: the disease and the putative cause of the disease (the exposure or risk factor). Four methods are generally used in such a formulation: difference, agreement, concomitant variation, and analogy. A causal hypothesis can be generated by looking for the difference between two situations, one that leads to disease and the other does not. The difference(s) between the two situations may be the putative cause of the disease. Agreement involves similarities between different situations that lead to the same disease. The common factor on which the similarity or agreement is based could be the putative cause of disease. If variation in a putative causal factor is always associated with concomitant variation in disease occurrence, then that factor is likely to be etiologically important. The method of analogy is used to generate a causal hypothesis by looking at a causal relation between two phenomena and understanding its mechanism. If that mechanism is relevant to another disease situation, then the cause in the first instance could also be the cause in the second instance. Hypotheses must be specific and testable. Empirical data is from experimentation and observation. The conclusions from testing a hypothesis can be rejection/non-rejection and never acceptance. A new hypothesis is generated from the conclusion and the process is repeated. Use of the scientific method implies among other things that epidemiological knowledge is never stable. It keeps on changing and getting nearer the truth as new information is discovered.

C. SOURCES OF EPIDEMIOLOGICAL DATA

OVER VIEW

Epidemiological data can be sourced from observational or experimental studies. The bulk of epidemiological studies are non-experimental. Non-experimental studies are much cheaper and easier to undertake than experimental studies. A major attraction of the epidemiological non-experimental study is that it is generally a cheap source of data on human disease and appropriate risk factors.

EXPERIMENTAL STUDIES

Definition: Experimental studies involve deliberate human action or intervention whose outcome is then observed. Their objective is to establish the definitive causal relation. The following are examples of experimental studies involving humans: clinical therapeutic trial, community intervention study to assess vaccines, community intervention to assess preventive measures, and animal bio-assays. In 1753 Dr Lind carried out one of the first experimental studies on humans. He studied 12 sailors who were given a standard diet. They were allocated to 6 treatment groups that received various treatments for a period of 14 days. The main characteristics of an experimental design are random selection, random assignment, manipulation of independent variables by the experimenter, and control of all other variables by the experimenter.

Types of experimental studies: Experimental studies are of two types: natural experiments and true experiments. Natural Experiments can be analysed to provide insight at little cost to humans. They are experiments that humans do not design but can observe. Classical examples of natural experiments are: Snow's study of cholera in London, the study of air pollution episodes leading to mortality in London and Los Angeles, and the study atomic bomb survivors in Hiroshima and Nagasaki. True experiments are more involved and expensive than observational studies or natural experiments but are still cheaper and easier than laboratory-based research. Classical examples of true experiments are: Lind's trial of fruit juice for scurvy in 1747, Jenner's cowpox vaccination in 1796, study of the mosquito-yellow fever relation by Findlay in 1881 and Reed in 1900, the induction of pellagra by Goldberger and Wheeler in 1915, the discovery of the relation between rice and beri-beri by Fletcher in Kuala Lumpur in 1905, and tests of the prevention of dental caries by fluoridation carried out by the United States Public Health Service (USPHS) in 1970. Imperfect epidemiology is a term used for quick and dirty data collection methods. For example an illiterate village headman could be trained to collect a minimum data set that is used to make simple diagnoses. Capture-recapture methods, adapted from wild-life studies, are used in situations where population denominators are not available.

Study population: A study population suitable for the problem being studied must be selected. It may represent the general population or may be restricted to certain groups. A representative sample is not necessary for validity of an experimental study. Economic and logistic considerations affect the selection of the study population.

Study groups: The researcher determines the experimental or intervention group (who will get the exposure studied) and the comparison group. The control group could get the exposure studied unknown to the investigator. Even after randomization the experimental and comparison groups may not be comparable.

End-points: The end-points of the study must be defined precisely.

Randomization The concept of randomization was introduced by RA Fisher in 1923. Randomization is the basic sampling scheme for experimental studies and clinical trials. It is the main sampling design used in experimental studies. The objective of randomization is to prevent investigator bias in selection and allocation of subjects to the treatment and reference groups, ensure comparability of results from the two groups, and increase confidence in the results of the study. Where randomization and selection of a good control group are not possible, quasi-experimental studies may be carried out. Randomization involves allocation of subjects by independent random choice to 2 or more experimental groups. Randomization can be achieved by use of random numbers. There are other methods of randomization that randomly allocate subjects entering study in a short interval of time to the different groups. Randomization has the objective of balancing the distribution of confounding factors, known and unknown, across groups. This purpose is not always achieved to 100% perfection. To obtain more balancing of confounding randomized block design is used in which the randomization process is carried out separately for each 'block'. The block could be a gender or age group. Once the 2 groups are identified, the study may be carried out in parallel or it may use the cross-over design. In the former the experimental and comparison groups are followed until the end. In the latter there is an exchange. The experimental group becomes the comparison group during the trial and vice versa. Thus subjects in both groups will take turns to receive the material being tested. Non-randomized trials can be carried out where randomization proves difficult but they are far less valid than the randomized ones. They obtain comparison groups by using either historical controls or by carrying out pre and post test assessments.

Strengths of experimental studies: The main strength of experimental studies is good control for confounding. Randomization in experimental studies is the basis for unequivocal evidence of causality. The experimental design enables the investigator to control extraneous variables. The experimental design enables the investigator to vary the levels of independent variables in order to make a more thorough and detailed study.

Weaknesses of experimental studies: The main weakness of experimental studies is that well controlled experiments on humans are difficult to carry out and have ethical problems. It is difficult to put humans under full experimental conditions where they can be observed for 24 hours. Ethical controversies and violation of human rights always arise in such studies.

NON-EXPERIMENTAL OR OBSERVATIONAL STUDIES

Definition: Observational studies allow nature to take its course and just record the occurrences of disease and describe the what, where, when, and why of a disease. Natural experiments may be considered a type of observational study. They usually precede and prepare for definitive experimental studies. They may be descriptive or analytic. Descriptive studies may provide information on incidence and prevalence by factors such as socio-economic status, sex, place. Analytic studies are concerned with etiology. Two types of comparison are employed: disease in exposed vs. disease in non-exposed & exposure in diseased vs. exposure in non-diseased. Observational studies have been crucial in leading to causal discoveries as shown in the following 6 examples. The increasing deaths from lung cancer in the first half of the 20^th century and cigarette smoking; oral contraceptives and venous thrombosis; congenital cataract and intra-uterine rubella infection; low rates of dental decay in populations with mottled teeth living in municipalities with a high fluoride water content; Burkitt’s Lymphoma in low altitude and high rainfall areas that have high malarial infection; and increasing demand for pentamidine to treat P. carinii pneumonia and the HIV/AIDS epidemic.

Quasi-experimental and correlational observational studies: Non experimental designs may be quasi experimental or correlational. Quasi-experimental studies are those in which 2 groups that were not assigned randomly are compared or are studies in which assignment is by nature. Correlational studies measure two attributes of the same subject to see how they relate to one another. Regression and correlation are two statistical procedures used for correlational studies. Correlational studies have three main advantages: ability to analyse variables like age or gender that the investigator can not manipulate, absence of ethical problems associated with experimental studies, and shorter observational times compared to experimental studies.

Different designs of observational studies: Observational epidemiological studies have basically three designs based on the method of sampling: cross-sectional, case control, and follow-up. Cross-sectional studies, are also known as prevalence studies, require new data collection at a point in time. Ecologic studies, a type of cross-sectional study, correlate disease frequency to locality using pre-existing data. Cross sectional studies are based on non-fixed sampling and disease may precede exposure or vice versa. Case-control studies compare distribution of risk factors in diseased individuals (cases) and disease-free individuals (controls). In a case control study disease is fixed at the start and the diseased are studied to find the exposure. Follow-up studies also called cohort or prospective studies enable study of temporal relations that may be prospective or retrospective. In follow up studies the exposure is fixed at the start of the study and exposure precedes disease. Observational studies may be prospective or retrospective. Either variety can be case control or cohort.

Strengths: Non-experimental or observational studies are easy, convenient and cheap. They enable us understand causes of disease by formulating and testing hypotheses, explain local disease patterns, describe natural history of disease (death, survival or cure, and complications), and for administrative uses (health resources needed). The main advantages of observational studies are their low cost and lack of ethical controversies. A cheap study is made of a wide variety of human experiences by just observing and recording information. This is much cheaper than experimental studies in which people must be subjected to various treatments and exposures at the experimenter's cost. Ethical problems in observational studies are much less than those in experimental studies because the human subject is not exposed to any major physical risk.

Weaknesses: The non-experimental design has no random assignment or control over all conditions making it liable to confounding effects. Several unplanned co-factors (giving rise to confounding, interaction or effect modification) are involved making interpretation difficult. Experimental studies, unlike observational studies, collect systematic information on these co-factors rendering study interpretation easier. It is not possible to study etiology directly in observational studies because the investigator does not manipulate the exposures. Etiology is studied only indirectly by comparing disease experience in the group exposed to a putative risk factor with the group that was not exposed. Information on the variable of interest may not be available recourse being made to surrogate variables. Mortality and prevalence can be used as surrogate variables for incidence, the variable of interest. They are however not perfect representations of incidence.

Choice of study design: In the situation of equal sample sizes and for a given total sample size, the case control design is superior to both cross-sectional and follow-up designs in power and precision (length of confidence interval). The case control design yields a more powerful chi-square than a cross-sectional survey in all situations. The case control design yields a more powerful chi-square than a follow-up design if the disease is rarer than the exposure. Each type of design is preferable in a given set of circumstances. The follow-up design is best for etiological studies because the time sequence is known. It is also preferred for common, severe, and easily observed disease that only need a short follow-up. The case-control design is best for etiological study of rare diseases. It is usually a preliminary study to be followed by follow-up or experimental study. The experimental design is used for the final proof of causality or efficacy of intervention

Selecting populations for epidemiological study: There are basically four ways of identifying populations for epidemiological study: geopolitical areas (village, town, district etc), lists of households, restricted or institutional such as special registers and schools, and health insurance data bases. Four considerations are made in the process of population selection: representativeness, accessibility, accuracy of the population denominator, and the desired study size.

Sample size: Observational studies may use equal or unequal sample sizes. The factors involved in making sample size determination are the difference worth detecting, the level of significance, and the test statistic. The sample size may be computed or read off tables

EXISTING DATA:

The following are data sources that are collected routinely for other purposes but can be used by the epidemiologists at virtually no cost to them: census, medical facilities, government, and private sector, health surveys, and vital statistics. This data is usually not sufficient for a full epidemiological inquiry for two reasons: it may not include all the data elements of interest and it may not be sufficiently accurate. Health and health-related data is found in the national census reports. Census data also provides denominators as well as ideas on sampling frames. Health/medical facilities such as hospitals, clinics, and specialized treatment centers collect a lot of data on a routine basis that can be useful epidemiologically. Government institutions such as the Ministry of Health, other ministries, and institutions (police, military, prison, and educational) collect data routinely much of which is of epidemiological importance. Private sector organizations such as health and life insurance companies have extensive records with health and demographic information on their subscribers. Health Surveys are carried out for specific health problems or for assessing the general health of the population. A lot of epidemiological data can be obtained from vital statistics databases on birth, death, marriage, & divorce.

D. EMPIRICISM, INDUCTION, REFUTATION, and BAYESNIASM

EMPIRICISM

Epidemiological methodology employs the scientific method. It is empirical, inductive, and refutative. Epidemiology relies on and respects only empirical findings. There is no room for preventive action being based on pure reasoning, rationalism, not subjected to empirical verification by collection and analysis of data. Empiricism refers to reliance on physical proof

INDUCTION

Induction is a type of reasoning that starts from one observation and generalizes to an explanatory theory. In 1620 Francis Bacon in his Novum Organum presented an inductivist view of science which is making generalizations (or inductions) from specific observations to general laws of nature. This is the converse of deductive inference in which we start with a theory and then predict the observations. Progress of science requires use of both inductive and deductive inference. Both inductive and deductive logic are used in epidemiological reasoning. The inductive is used more because it is more in line with empirical experimental verification.

REFUTATION

The concept of refutation was developed by Karl Popper who reasoned that science grows by conjecture followed by refutation or falsification. Refutation is a type of scientific reasoning introduced by the philosopher Karl Popper that emphasizes rejection of suppositions rather than accepting them. This is in line with the spirit of empirical scientific enquiry which never closes the door to further ideas by accepting any idea as conclusive. Rejecting an idea opens the way to test other ideas. Based on the scientific method, epidemiology can refute a finding but can never offer conclusive proof. This is in line with the spirit of empirical inquiry that knowledge and understanding grow continuously and facts accepted and interpreted in one way today may be rejected and interpreted in another way tomorrow. Karl Popper argued that a theory is scientific if it is falsifiable. Any assertion that is not falsifiable is not considered scientific because it can not be subjected to scientific experimentation.

BAYESIANISM

Bayesianism was originated by the Reverend Thomas Bayes. It provides a way of changing prior probabilities into posterior probabilities. In other words it enables a person to start with a prior belief that is modified by the empirical observations.

PROBABILITY AND DETERMINISM

In scientific inference probabilistic models are used more than deterministic models. There is an underlying deterministic order to physical phenomena that humans do not know and can not measure. Probabilistic models are therefore used as a necessity. Thus science is probabilistic. The better the research design the higher the probability of the truth.

RELATIVITY and ABSOLUTISM

Limitations of human intellect and observations make human knowledge relative and never absolute. This leaves the door open for further scientific investigations since none of the scientific facts is absolute.

E. BALANCE OF STRENGTHS AND WEAKNESSES:

Many can be disappointed that epidemiology is not as deterministic as is laboratory science yet it has many strengths that compensate for this lack of precision. In a 1979 seminal discussion of the strengths and weaknesses of epidemiological methodology, Brian McMahon, Professor of epidemiology at Harvard, summarized the strengths as obtaining observational data cheaply and with a wide range of human exposures. The humans both choose and pay for the exposures and what the epidemiologist does is to collect the data. He identified the major weakness as inability to offer conclusive proof of the disease-exposure relationship. In this sense epidemiological findings open the way for further work and verification by laboratory science. As more epidemiologic studies indicate the same etiology, increasing convincing evidence is obtained. However the final proof will have to come from the laboratory. In some cases the final proof is never obtained. Using the limited epidemiological knowledge on causation, public health interventions may be undertaken and they result in elimination of the disease before the laboratory workers have a chance to say their word.

One of the strengths of the epidemiologic methodology is the possibility of successful intervention against disease based on preliminary and not full understanding of the causal pathway. Effective measures had been taken against diseases by the time Louis Pasteur discovered the microbial basis of epidemic disease in 1865. Wynder EL (1994) in an article in the American Journal of Epidemiology 139:548 listed examples of diseases for which preventive measures were undertaken before the causes were fully understood. Dr James Lind discovered that lemon could prevent scurvy in 1753 but it was not until 1928 that A. Szent-Gyorgi discovered ascorbic acid deficiency as the cause of the disease. In 1755 CE Gaga discovered the prevention of pellagra but its etiology due to niacin deficiency was discovered by J Goldberger et al in 1924. In 1755 Percival Pott discovered the prevention of scrotal cancer as avoiding soot from chimneys; in 1933 JW Cook et al discovered Benzo (alpha) pyrene as the carcinogen. In 1798 Dr Edward Jenner discovered that vaccination could prevent smallpox but it was not until 1958 that F Fenner discovered the orthopoxvirus as the cause of smallpox. In 1847 J Semmelweiss discovered that washing hands prevented puerperal fever but it was not until 1879 that Louis Pasteur discovered the streptococcal bacterium that caused the infection. In 1849 John Snow (1813-1858) discovered that contaminated water caused cholera but it was not until 1893 that Robert Koch discovered vibrio cholerae. Snow using careful observations found that cholera incidence was 5-10 times more in households supplied by the Southwalk & Vauxhall Company that obtained its water from the polluted downstream parts of the Thames River. In 1895 L Rehm discovered the association of bladder cancer with occupation in the dye industry but it was not until 1938 that WC Harper et al discovered the carcinogen as 2-Napththylamine. In 1901 W Reed et al discovered the role of mosquitoes in the transmission of yellow fever but it was not until 1928 that A Stokes discovered the causative organism, flavivirus. In 1915 R Abbe discovered the association of oral cancer with tobacco chewing but it was not until 1974 that D Hoffman et al discovered the carcinogen as N’-nitroisonornicotine.

1.1.4 HISTORICAL EVOLUTION OF EPIDEMIOLOGIC KNOWLEDGE

A. 1^st EPOCH: ANCIENT TIMES TO 1500 CE

EPIDEMIOLOGY and PUBLIC HEALTH

The historical evolution of epidemiological knowledge has paralleled that of public health practice because of the close relationship between the two disciplines. There are some who even consider them to be just one discipline. Epidemiology is a basic or foundation science for public health.

ANCIENT TIMES (UP TO ABOUT 500 AD).

Review of the historical record shows that the ancients knew and used epidemiologic principles of disease prevention by environmental sanitation and personal hygiene. They were however not consciously aware of a separate discipline called epidemiology neither did they have a special word for it. The Mojenjo-Daro city was built 4000 years ago in Northern India. It had paved streets covering sewers that drained bathrooms located in well built homes. The Minoan and Mycenaean cultures were Aegean civilizations (3000-1500 BC) that had public water systems, drainage canals, and flushing toilets. Babylonians knew about disease transmission by insects. They also isolated the sick presumably to prevent spread of infection. The early Egyptians were concerned with public hygiene. The Hebrews were concerned about excreta disposal; hygiene (personal, food, and water), and isolation of lepers in colonies away from the community and forcing them to wear special costumes. The Greeks believed that disease was due to human and ambience factors. They knew about contagion by air. They also knew about sanitation & hygiene. Hippocrates (460-377 BC), reputed to be the father of modern medicine, taught that disease is connected to the human environment. Hippocrates laid the foundations of scientific medicine. He studied medicine without the constraints of philosophy and superstition. He stressed the importance of the environment to health. Romans were involved in public works of public health importance such as public latrines, water supply, drains, and public baths. The Romans had freshwater that came via aqueducts. They had good roads that were swept and repaired. They had systems for cleaning public baths and toilets. Taverns and inns were inspected. Garbage was collected and was disposed of properly.

EUROPEAN MIDDLE AGES (500 - 1500 CE):

This period following the collapse of the Roman Empire witnessed a general decline of scientific knowledge. Greek and Roman science was forgotten in the general European decline that ensured the fall of the Roman Empire. The period also witnessed decline of public sanitation. Epidemics of leprosy, smallpox, malaria, and syphilis were common. Other unrecorded infectious diseases were also common. In about 1400 CE the Venetians introduced quarantine to control disease. Plague was the most devastating epidemic disease. It spread from Egypt to Europe and other parts of the world. By 1340 it had killed 13 million people in China and had almost depopulated India. Frequent plague pandemics ravaged Europe in 542-543 CE and 1348-1349 CE. The 14^th century CE witnessed a plague pandemic in Europe. In 1348 CE plague attacked Paris, London, Venice, and Florence killing many people. The great plague in Britain of 1664 CE killed many people. Plague was known to be contagious but its agent was not known. By the middle ages, Europeans were better prepared to control plague by using measures of isolation and seaport quarantines.

MUSLIM ERA (WEST ASIA, NORTH AFRICA, and ANDALUSIA: 800-1500 CE):

The Muslim state, dar al islam, that was established in West Asia, North Africa, and the Iberian peninsula, was a great patron of learning and science. Conditions of peace and stability over a wide expanse of territory under one governance encouraged diffusion and exchange of ideas on health and disease. The Prophetic teachings on contagion, diet, hygiene (dental, body, place, clothes, and utensils) gave the initial stimulus to medicine and public health in the new Islamic civilization. He taught the importance of personal body hygiene which was revolutionary. Muslims have to wash 5 times a day before each prayer. Toilet hygiene was taught in detail to avoid any urinary or fecal contamination. He taught concepts such as contagion by advising the sick not to visit the healthy. It is also clear in some hadiths that he considered some diseases non-contagious. Muslims knew epidemics and the use of quarantines. The Prophet had taught that people should not enter or leave an area with an epidemic. Omar Ibn al Khattab had to turn back from his visit to Syria because of the ‘Awamis plague. Abubakr Al Razi described the contagiousness of small pox and measles. Muslim cities were clean, spacious, with drains, paved streets, and well-ventilated buildings. Hospitals were clean and were in good location in relation to the wind patterns to minimize infection. Muslim had a major impact on European medicine. Crusaders took back advanced medical knowledge to Europe. Europeans learned medicine directly in Muslim universities in Andalusia. Muslim intellectual stimulus led to the European renaissance

B. 2^nd EPOCH: 1500-1750 CE

NEW IDEAS

The renaissance (1400-1600 CE) was a period of new ideas in Europe. Copernicus, Galileo, and Leonardo da Vinci introduced new and stimulating ideas in Europe. As a result scientific investigation and inquiry grew. By mid 16^th century, leprosy, tuberculosis, plague, scabies, small pox, influenza, and syphilis were recognized as separate diseases. There was little development of public health services or practices during and after renaissance. However there was significant growth of medical knowledge. There were also major discoveries or developments. This was a period of scientific curiosity, empiricism, and exploration. Improved means of communication ensured rapid spread of ideas in Europe and beyond. Francis Bacon (1501-1626 CE) introduced the empirical method into Europe which was an impetus to experimentation and growth of empirical knowledge. Francis Bacon published Norvum Organum which presented an inductive view of science that makes generalizations from observations to general laws of nature. In 1739 CE the Scottish philosopher David Hume described a deficiency in the inductive approach. The inductive process assumed that events in the future would follow the same pattern which had no basis. He argued that proof using induction was not possible. Karl Popper addressed Hume’s problem by proposing that science advances by conjecture, refutation, and falsification. Scientists form hypotheses that are then tested by experiment. The Bayesian approach then came to address problems found in both induction and deduction. The Bayesian approach solves the problem of requiring 100% certainty for premises. Prior probabilities are transformed into posterior probabilities using data.

SPREAD OF DISEASES

Microbial unification of the world started with the age of exploration in 1500 CE onwards. Increased population mobility led to the spread of new contagious diseases such as syphilis, small pox, measles, TB, and rabies. Microbial diseases ceased to be confined to specific geographical areas or specific groups of persons. Proof of wide-spread contacts was the denial of responsibility for introduction of syphilis in Europe. Although initially considered a novelty and a disease of the well-placed that gave pride and indicated sophistication, it became later to be hated and feared. It was variously called a French disease, an Italian disease, and a Turkish disease depending on who was speaking or writing. Introduction of smallpox into Latin America led to widespread population devastation.

PIONEERS and NEW DISCOVERIES

Girolamo Fracastoro (1478-1553 CE), known as the first European epidemiologist, published the book ‘De Contagione Morbis’ in 1546 CE. He proposed the theory that disease spreads by direct contact and that disease is transmitted by small living particles. He however knew nothing about microorganisms. In 1619 CE quinine (cinchona bark) was found to be effective against malaria. In 1683 CE Van Leeuwenhoek saw protozoa and bacteria under the microscope that had been discovered by Galileo Galilei. Variolation was introduced into Europe from Turkey by Lady Montague in 1721 CE as a forerunner to vaccination. Benedino Ramazzini wrote about occupational disease in his book ‘De Morbis Artificum Diatriba’ published in 1700 CE. James Lind (b. 1716) found cure for scurvy. The theory of spontaneous generation was disproved by the work of Redi (1686?) and Abbe Lazzaro Splanzani (1729-99). Captain John Graunt published 'Natural and Political Observations Upon the Bills of Mortality' in 1662 and made significant epidemiological observations and determinations: seasonal fluctuations in cause-specific death rates, estimation of the population of London, excess of female over male births, excess of male age-specific death rate over female age-specific death rates, and construction of the first population life table. He started modern epidemiological thinking and is credited with introducing the following epidemiological methods: summarizing voluminous data, description of data, and interpretation of data.

C. 3^rd EPOCH: 1750 - 1870 CE (sanitary epoch)

NEW EPIDEMICS

In this period, epidemics of disease occurred in the new world. In 1773 CE yellow fever killed 4047 persons in Philadelphia. The epidemic recurred in 1797 CE, 1798 CE, and 1803 CE. Dr Benjamin Rush traced yellow fever to the docks where ships arrived from tropical areas. It was falsely thought at that time that yellow fever was due to vapors of decaying coffee beans kept in port warehouses.

QUARANTINES, SANITATION, and VACCINATION

The third epoch can also be defined as the sanitary stage of epidemiological development. Health was defined in a negative way as a state of absence of disease. It was known that diseases follow natural laws. The pathology of many diseases was known in detail. It was appreciated that disease was due to environment but there was a dispute whether this was due to an agent or to contagion vaguely defined as miasma. The approaches to prevention reflected the supposed cause. Those who believed in contagion emphasized quarantine and vaccination. Those who believed in miasma emphasized sanitation. There were also disputes about causation/prevention. Some believed that disease was pre-destined whereas others believed that there was a role for human will and action in disease causation and prevention. Those who believed that human will could alter the course of disease undertook active measures to prevent disease. Those who believed purely in pre-destination felt powerless against disease and did not think of any specific interventions. They thought that epidemics were punishments from God for sins and had little incentive to investigate and prevent disease.

INDUSTRIAL REVOLUTION and URBAN POVERTY

With the industrial revolution there was an urban drift and urban poverty that changed the picture of public health as we shall see later. It was thought that disease and poverty were a consequence of moral failure. Those addicted to alcohol or with other social diseases became victims of poverty and disease. There was a failure of appreciation of the fact that the urban poor were trapped in genuine poverty living in an unhealthy environment and having insufficient material resources to improve their condition.

MECHANISTIC AND NON-MECHANISTIC VIEW OF DISEASE

Most of the 19^th century witnessed a debate between two opposing explanations of disease occurrence. The mechanistic view held that disease was due to contagion and microorganisms. The non-mechanistic view held that disease was due to the environment and the term miasma was used to refer to non-specific environmental causes of disease. The non-mechanistic camp emphasized the importance of hygiene in disease prevention. From our modern understanding we realize that both sides had some elements of truth. Modern epidemiological concepts agree that the environment interacts with microbial agents in the causation of disease.

PIONEERS

The period witnessed many major discoveries. In 1798, Edward Jenner (1749-1823) became a pioneer of vaccination when he found that material from cowpox lesions prevented small pox. Charles Turner Thackeray published ‘The effects of Arts, Trades, and Professions on Health and Longevity’ in 1783 CE. In 1846 CE, Peter Ludwig Panum (1820-1885) studied measles in the Faroe Islands, calculated its incubation period as 13-14 days and found differences in host susceptibility. In 1840 CE Henle published a treatise on the germ theory of disease. Louis Pasteur (1822-1895 CE) and Robert Koch (1843-1900 CE) expanded the germ theory through experimentation. Fungal diseases were described muscaridine by Agostino Bossi in 1835 CE and favus by Schoenlein in 1839 CE. Ehrenberg introduced the terms: bacterium, vibrio, spirillum, and spirochete in 1838 CE. Ignaz Philip Semmelweis suggested hand-washing by obstetricians to avoid infection in 1847 CE. This resulted in the fall of maternal mortality. Rayer & Davaine described rod-shaped organisms in animals dying of anthrax in 1850 CE. In 1842 the public health reformer Edwin Chadwick published a report on the bad health conditions in the industrial cities. The report stimulated initiation of several public health measures that contributed to the emergence of the sanitary reform movement in England and later all of Europe. In 1851 CE the International Sanitary Conference met in Paris. Percival Pott, a pioneer of occupational health, found in 1775 a high rate of scrotal cancer among chimney sweeps and attributed it to soot that lodged in the scrotal skin.

MEDICAL STATISTICS

William Farr was in charge of medical statistics for England and Wales in 1839 and continued in the same position for 30 years. He was a physician with interest in numbers. He had many achievements credited to his name: start of the discipline of vital statistics as a system of regular collection and interpretation of data, study of mortality in various groups (miners, prisoners, and by marital status), study of cholera, literacy rate, life-time monetary value of a person, and computation of the attributable rate. Farr understood the following modern epidemiological concepts: person-time, standardized mortality rate, dose-response, herd immunity, prevalence as a function of incidence and disease duration, retrospective and prospective studies.

D. 4^th EPOCH: 1870- 1945 CE (Infectious disease epoch)

MAJOR CHANGES

The industrial revolution brought new problems. Urban poor housing, sewage disposal, and polluted water led to disease. There was concern about the health consequences of industrialization. Infectious diseases such as cholera, typhus, typhoid, and diphtheria were still the leading causes of death. Knowledge of bacteriological and nutritional causes of disease advanced in this period. There was rapid growth of scientific knowledge and bio-technology. The holistic view of health held since the earliest time was replaced by the disease or pathological perspective. This change in paradigm had both negative and positive effects. The negative effect was the failure to treat the patient as a complex human with many needs and problems. The positive was the focusing of energy that enabled rapid development of specialized knowledge. The germ theory of disease triumphed over the theory of miasmas. With this the microbiological age in medicine was ushered when all human diseases were investigated and managed from this perspective. It was many years later that this view was modified when it was realized that many diseases were not due to infectious agents.

MICRO-BIOLOGICAL BASIS OF DISEASE

Several discoveries in this period established and anchored the microbial basis of disease. Joseph Lister had introduced antiseptic surgery in 1865 with good results. The concept of water-borne infection was appreciated when In 1872 CE John Snow showed that the London cholera epidemic was due to polluted water. William Budd in 1857-73 studied typhoid and concluded that it was contagious. Louis Pasteur (1822-1895 CE) established the microbial cause of disease when he proved that germs (micro-organisms) caused specific diseases. He showed that fermentation failed if organisms from the air were excluded. Bacteriology as a science owes a lot to Dr Robert Koch (1843-1910 CE) who is credited for being the father of bacteriology. He established that polluted water was a cause of epidemics. He identified causative organisms of anthrax in 1876 CE, tuberculosis in 1882 CE, and cholera in 1883 CE. He developed the Koch’s postulates (Bowman p. 34.2) used to establish a causal link between a disease and an organism.

The period up to 1910 CE can be called the bacterial age because most bacterial agents were discovered during that period. From 1910 CE onwards most discoveries of agents were viruses. In the 1970s and onwards a few bacterial and parasitical agents were discovered. The discovery of bacterial causative agents preceded the discovery of vaccination by few years. Killed vaccines were developed before live attenuated vaccines. The anthrax bacterium was discovered in 1849-1855 CE and its vaccine was developed by Pasteur in 1881 CE. The rabies virus was discovered in 1936 CE by Webster and Chow but its vaccine was developed by Louis Pasteur in 1885 CE. The tubercle bacillus was discovered in 1882 CE by Robert Koch. The tuberculin test was developed in 1892 CE and BCG vaccination was developed in 1924 CE. The diphtheria bacterium was discovered by Klebs and Loeffler in 1884 CE. Diphtheria anti-toxin treatment was developed in 1890-1894 CE. The Diphtheria antitoxin immunization was developed in 1912 CE. The Schick test for diphtheria was developed in 1913 CE. The cholera bacterium was discovered by Robert Koch in 1894 CE and the killed cholera vaccine was developed in 1896CE. The typhoid bacterium was discovered by Gaffky in 1890 CE and anti-typhoid immunization was developed in 1896 CE. The plague bacterium was discovered in 1894 CE by Yersin and its vaccine was developed in 1895 CE for animals and 1906 CE for humans. The tetanus bacterium was discovered in 1884-1889 CE. The tetanus anti-serum was developed in 1890 CE and anti-tetanus toxoid immunization was developed in 1933 CE. The pertussis bacterium was discovered in 1906 CE by Bordet and anti-pertussis vaccination was developed in 1931-1939 CE. The typhus agent was described in 1909 CE by Ricketts and in 1916 CE by Rocha-Lima. The killed Rickettsia vaccine was developed in 1942 CE. The gas gangrene agent was discovered in 1892 CE by Welch and its antitoxin was developed in 1916 CE.

Viruses were discovered towards the close of the 19^th century when Ivanosky discovered the first virus, the tobacco mosaic virus (TMV) in 1892. The period after 1910 CE can be called the viral age because most viral agents were described in this period. Smallpox virus was described by Noguchi in 1915 CE but variolation had been practiced in China in circa 1000 CE and circa 1750 CE in Europe. Edward Jenner had carried out vaccination in 1798 CE. Panum studied measles in the Faroe Islands and described life-long immunity as well as cycles of epidemics. The influenza virus was discovered by Smith et al in 1931 CE and its vaccination was developed from the early 1950s onwards. The yellow fever virus was discovered in 1928-1933 CE and its immunization was developed in 1928 CE by Hindle. The poliomyelitis virus was discovered in 1910 CE by Lansteiner and Flexner et al). The killed polio vaccine was developed in 1954 CE by Salk and the live attenuated vaccine was developed in 1961 CE by Sabin. The measles virus was discovered in 1954 CE by Enders. The measles vaccine was developed in 1960 CE and was licensed in 1963 CE. The mumps virus was discovered in 1945 CE by Johnson and Goodpasture. The killed mumps vaccine was developed in 1948 CE and the live attenuated vaccine was developed in 1967 CE. The rubella virus was discovered in 1962 CE by Weller and Neva. The rubella vaccine was developed in 1966 CE and was licensed in 1970 CE.

In the 1970s discoveries of new agents was confined almost entirely to viral agents. Hepatitis A virus was discovered in 1973 CE by Feinstone et al. The Rotavirus was discovered in 1973 CE by Bishop et al. The Hepatitis B virus was discovered in 1970 CE by Cane and its vaccine was developed in 1978 CE. The Ebola virus was discovered in 1977 CE by Plot et al. The Hantavirus was discovered by Johnson and Lee in 1977 CE. The Human immunodeficiency virus (HIV) was discovered in 1983 CE by Montaignier at al. The Hepatitis C virus was discovered in 1989 CE.

A few bacterial agents and parasites were discovered in the 1970s onwards. The agent of Legionnaire’s disease was discovered in 1977 CE by Fraser, Mcdade et al. Helicobacter pylori was discovered in 1983 CE by Marshall and Warren. The Lyme disease agent was discovered in 1982 CE by Steere et al. (page 5 John M Last: Public Health and Human Ecology. 2^nd edition. Prentice Hall International, Inc ? year)

Knowledge of vector-borne disease advanced when Manson Barr, Bruce-Chwatt and others studied the transmission of mosquito-borne infections, malaria and yellow fever. The transmission of Chagga's disease was also elucidated.

The basis for further growth of laboratory medicine was laid by the first use of diagnostic serology by Cruhn, Durham, & Widal (1891). Later Jules and Bordet discovered antibody and complement.

NON-INFECTIOUS DISEASES

Neoplasms: In this period cancer increasingly became a major cause of death due to increased longevity and environmental exposures.

Nutritional diseases were described. Beri-beri was first described by two Dutch physicians, Bontius in 1642 and Nicolaas Tulp in 1652, in a young Dutchman brought back from the Far East with what was known at that time as beriberi or lameness. Its association with milling of rice was described in a brilliant experiment at Kuala Lumpur Hospital in 1905. Scurvy had been described by Lind, a naval surgeon, in 1747. Pellagra was described by Wheeler & Goldberger in 1915. Before Goldberger's epidemiological studies, pellagra was thought to be due to micro-organisms and not due to dietary deficiency. Elmer McCollum became a Professor at Johns Hopkins in 1918 and in a series of experiments discovered vitamin-deficiency diseases. Soon occupational disease, psychiatric disease, and environmental disease were identified and were studied.

STATISTICS

Statistical theory and practice developed rapidly towards the close of the 19^th century to keep up with developments in basic research and public health all of which required statistical analysis. Sir Francis Galton derived the correlation coefficient. Karl Pearson discovered the chi square statistic.

CHEMOTHERAPY

Paul Erlich discovered arsenic compounds as the first effective anti-microbial agents. Alexander Fleming discovered penicillin in 1929 CE but its mass production had to wait until the Second World War. Domagk discovered sulfonamides in 1935 CE.

CONVERGENCE OF THE MECHANISTIC and NON-MECHANISTIC VIEWS

The non-mechanistic views (environment, social, and behavioral basis of disease) converged with the mechanistic view (molecular, biological, gent-host interaction).

PIONEERS

In 1897 Emile Durkheim published a book ‘Suicide: A study in sociology on the relation of suicide to psychopathological states, race, heredity, climate, season, behavior, and other social phenomena’. The book became a pioneer of social epidemiology. In 1914 Joseph Goldberger became a pioneer of nutritional epidemiology by publishing a paper relating pellagra to diets high in cereal and caned foods and free of fresh animal products.

E. 5^th EPOCH: PERIOD OF MODERN EPIDEMIOLOGY 1945 – today (chronic disease epoch)

MAJOR DEVELOPMENTS

Broad view of health: Health was defined in a broad sense as: physical, mental, psychological, and spiritual well-being. The concept of holistic health was reintroduced. There was a shift from infectious to chronic disease. Scientists recognized the multi-causal nature of disease: genetic, psycho-social, physiological, and metabolic. There is concern with pollution, smoking, and nutrition.

Epidemiologic transition: There was overall fall of mortality. The male-female gap in mortality increased due to genetic and behavioral factors (especially smoking). The rising life expectancy was due to fall of infant mortality, use of antibiotics, and medical technology especially in surgery. Infant mortality fell because of less infection, better nutrition, smaller family sizes, clean water supplies, control of vectors, clean milk, and immunization. Infectious diseases decreased while life-style related diseases increased. Shifting disease patterns became obvious between developed and developing countries. Incidence of chronic diseases increased in developed countries with the control of infectious diseases. There was little progress in the cure of chronic diseases; the emphasis remains on prevention. Poverty of resources prevented control of infectious diseases in developing countries.

Major epidemiologic studies: In this period major studies were undertaken. They helped redefine the direction of epidemiology and public health. The seminal studies that can be mentioned were: community-based intervention trial of water fluoridation, trials of the Salk vaccine, the Framingham Heart study, and the Report of the Advisory Committee to the Surgeon General of the US Public Health Service on Smoking and Health.

Biostatistics and computing: The availability of computers to collect and analyze large quantities of data helped in the growth of studies.

CIGARETTE SMOKING and LUNG CANCER

Two events are of major importance for the development of epidemiological knowledge. Case-control and follow-up studies of smoking and lung cancer were undertaken. These studies revealed the hitherto unknown link between smoking and lung cancer and helped launch chronic disease epidemiology as a serious discipline of epidemiology. In 1947 CE a case control study of lung cancer was undertaken in London hospitals. It compared smoking status was between those dying from lung cancer and those dying from other causes of death. In 1957 CE a cohort study was conducted by sending a questionnaire to all physicians asking about their smoking status. Physician death certificates were collected over the next 25 years to compare mortality among smokers and non-smokers.

CURRENT HEALTH PROBLEMS and CONCERNS

The current health problems of developed countries are: life-style related infectious diseases like HIV, chronic diseases, trauma (motor-vehicle and suicide or homicide), and mental disorders. The major determinants of health that have been identified are nutrition, environmental and occupational hazards, and life-style (cigarettes, alcohol, little physical exercise, marriage and social connections). Infectious disease still predominates in developing countries. As developing countries experience socio-economic growth they are beginning to pick up the disease pattern of developed countries.

CURRENT APPROACHES and STRATAGIES

Scientific approaches to resolving health problems are multi-disciplinary involving epidemiology, biostatistics, biological and physical sciences, social sciences, demography and vital statistics. The public health strategies of surveillance, intervention, and evaluation have resolved many problems. In the period between the end of World War II and 1960 the basic concepts of epidemiology were clarified. In the period 1960s - 1980s the theoretical basis of epidemiology was established. The discipline thence forward became more quantitative because of the computer revolution. The personal computer empowered the epidemiologist.

CHALLENGES and FUTURE DEVELOPMENTS IN EPIDEMIOLOGY

Developments in biotechnology and information technology provide new opportunities and challenges for the epidemiologist. New information from molecular biology will help study disease etiology at a more sophisticated level and will enable epidemiology to become more of an experimental discipline that depends on laboratory data more that observation and interview of people about their exposures. New biological and information technologies have enabled epidemiologists to probe more into the privacy of their study subjects which gives rise to new ethical issues of confidentiality and informed consent. Measuring and communicating weak associations is a new challenge to epidemiologists. The public and media are very interested in epidemiological findings but could be misled if weak associations are perceived to be causal relations that call for preventive action. Use of new computer technologies and statistical software will enable more sophisticated analysis of data. Environmental changes and demographic changes will continue giving rise to new disease and exposure patterns.

1.1.5 ETHICAL ISSUES IN EPIDEMIOLOGY

A. ETHICAL APPROVAL

B. INDIVIDUAL vs. COMMUNITY RIGHTS

There is sometimes a conflict between the requirement to protect the rights of the individual and protection of the community. Restrictions may have to be made on an individual in the public interest.

B. BENEFITS vs. RISKS

Public health interventions carry risks and costs that must be balanced against the benefits.

B. INFORMED CONSENT

Study subjects must be free to participate in the study, abstain from participation, or elect to withdraw from the study at any stage.

C. PRIVACY AND CONFIDENTIALITY

Data collected in an epidemiological study should not be released to any third party without consent of the subject. However such data can be subpoenaed by a court of law when public interest takes precedence over individual rights. Data is reported in the aggregate without any personal identifiers. Access to data is limited. There are issues that must be resolved: who owns the data? An epidemiologic study may uncover previously unrecognized disease. Pre-symptomatic disorders that do not require immediate medical attention cause no ethical problems. Disorders that require intervention create an ethical problem because the epidemiologist is required to breach confidentiality in the process of making sure that the patient gets the necessary care and that innocent persons will not be exposed to infectious disease.

D. CONFLICT OF INTEREST

Epidemiologists employed in academia can work relatively independently. Those working in government and industry are controlled by vested interests.

E. STUDY INTERPRETATION and COMMUNICATION

Risk reports that are not yet confirmed can be picked up by the media. It is difficult to keep epidemiological findings secret. Media have a tendency to sensationalize issues that complicates later intelligent debates. They may not understand differences among published epidemiological findings and over-blow controversies. These controversies are best evaluated by a careful study of the underlying evidence. MacMahon et al 1981 found that coffee causes pancreatic cancer whereas Feinstein et al. 1981 found that coffee did not cause cancer. Barefoot et al. 1983 found that type A personality was associated with heart disease but Shekelle at al. 1987 found that it was not. Vegetable-derived margarine had been thought to be good for the heart but Willet and Asherio 1994 found that it was bad for the heart. Falck et al 1992 found that pesticides caused breast cancer whereas Krieger et al 1994 found that they did not. Steinberg et al 1991 found that estrogen replacement therapy causes breast cancer whereas Kaufmann et al 1984 found that it did not. Beta carotene thought to prevent cancer was found by Omenn at al 1996 to cause cancer. Miller at al 1989 found oral contraceptives to cause cancer but the Cancer and Steroid Hormone Study Group of 1986 found that it did not (page 330 Ross C Brownson and Diana B Petiti: Applied Epidemiology: Theory to Practice. OUP New York and Oxford 1998). Study findings affect policy. Epidemiologists must know how to communicate risk to the public. It is an ethical obligation to report research findings to subjects so that they may take measures to lessen risk. Epidemiological evidence is different from legal evidence but fate sometimes determines that the two meet in a court of law. Epidemiological evidence may not be accepted in a court of law because it has few certainties; it is all probabilistic. Epidemiological evidence is concerned with populations whereas legal evidence pertains to individuals.

ILLUSTRATIONS

EXERCISES: TRUE/FALSE QUESTIONS

1. The following are true about the discipline of epidemiology

A. Epidemiology is the study of the distribution and determinants of disease

B. Epidemiology does not study injuries because they are not diseases

C. Epidemiology is not interested in the natural history of disease

D. Epidemiology studies disease after and not before its occurrence

E. The epidemiological triad consists of agent, host, & environment

F. The primary goal of epidemiology is to understand disease and not to prevent or control it.

TFFFTF

2. The following statements are true about the discipline of epidemiology

A. Epidemiology started as a study of epidemics of non-communicable diseases

B. Epidemiology is a methodological discipline with no coherent unified subject matter

C. Epidemiology is used for study of disease and is useless for non-disease phenomena

D. Qualitative epidemiology is more useful than quantitative epidemiology

E. Qualitative epidemiology is a type of study based only on high quality data

F. The bulk of epidemiological study today is qualitative

TTFFFF

3. The following statements are true about the discipline of epidemiology

Epidemiology is a basic discipline for preventive but not for clinical medicine
Epidemiology focuses on the community and not the individual
Epidemiology can be used to study the causes and consequences of war among humans
Epidemiological information has no contribution to health policy
The discipline of veterinary epidemiology does not exist

FTFFF

4. The following statements are true about classification of epidemiology

A. Most of epidemiologic study is observational

B. Observational epidemiology just describes human phenomena and cannot analyze them

C. Experimental epidemiology involves some form of intervention on humans

D. Theoretical epidemiology deals with mathematical and methodological issues

E. Public health practitioners do not care about theoretical epidemiology

TFTTF

5. The following statements are true about classification of epidemiology

A. Theoretical epidemiology is academic of not use to clinicians

Analytic epidemiology is based on the scientific method
Observational epidemiology is not based on the scientific method
Epidemiology mainly employs observational data that is cheap to obtain
Observational studies are more difficult to interpret

FTFTT

6. The following statements are true about classification of epidemiology

Experimental studies do not have good control of confounders
Laboratory data is not useful at all in epidemiology

C. Clinical data is not used at all in epidemiology

D. Descriptive epidemiology describes the patterns of disease occurrence in terms of place

E. Descriptive epidemiology is not interested in time of disease occurrence

FFFTF

7. The following statements are true about classification of epidemiology

A. Descriptive epidemiology studies characteristics of persons with disease

B. Analytic epidemiology studies causes of disease

C. Epidemiology is useful to public health and not to preventive medicine

D. Clinical epidemiology deals with diagnosis, management, and prognosis of disease

E. Hospital epidemiology is the same as clinical epidemiology

TTFTF

8. The following statements are true about sub-disciplines of epidemiology

A. Drug or pharmaco-epidemiology studies side effects and adverse reactions of drugs

B. Genetic epidemiology studies the genetic basis of disease

C. Molecular epidemiology studies the molecular basis of common diseases

D. Occupational epidemiology describes the types of jobs in a community

E. Environmental epidemiology studies the impact of air, water, and soil pollution on health.

TTTTT

9. The following statements are true about the activities of epidemiologists

Epidemiologists design studies and leave data collection to nurses
Epidemiologists undertake data analysis and leave its interpretation to clinicians
Epidemiologists are not involved in disease prevention
Epidemiologists are concerned with disease and have no interest in health promotion
Epidemiologists are not considered researchers since they do not work in laboratories

FFFFF

10. The following statements are true about famous epidemiologists

A. Hippocrates described the relation of disease to climate and geography

B. Hippocrates’s epidemiological descriptions were quantitative

C. John Snow discovered that London cholera epidemics were related to polluted water

D. William Budd described the spread of pneumonia

E. William Furr and Major Greenwood studied models of epidemics

TFTFT

11. The following statements are true about the epidemiologic methodology

A. Epidemiologic methodology is part of the scientific method

B. Epidemiological information cannot be sourced from existing data

C. Epidemiological information is sourced from new data collection

D. Experimental studies involve deliberate intervention on humans

E. Control for confounding is impossible in experimental studies

TFTTF

12. The following statements are true about epidemiologic methodology

A. Observational studies have no ethical issues at all

B. Observational studies can be used for definitive study of disease aetiology

C. Epidemiologic methodology is called empirical because it relies on physical proof

D. Inductive logic is used more than deductive logic in epidemiology

E. Intervention against disease has to wait for definitive proof of causality

FFTTF

13. The following statements are true regarding observational studies

Observational studies may be descriptive or analytic
Observational studies involve no intervention

C. Observational studies are more expensive than experimental studies

D. Observational studies are more difficult to undertake than experimental studies

Observational studies can study a wide variety of risk factors at the same time

TTFFT

14. The following are types of observational studies

Double blind clinical trial of a new drug in humans
Case control study of the relation between smoking and lung cancer
Study of toxicity of a new drug in animals
Follow-up studies of the relation between smoking and low birth weight
Randomized field trial of the effectiveness of a new vaccine

FTFTF

15. The following statements are true about the history of epidemiology

Girolamo Fracastoro first suggested that disease spread by small living particles
Van Leeuwenhoek was the first to see microorganisms under the microscope
Edward Jenner discovered vaccination against polio
Ramazzini wrote on occupational health in 1770
James Lind carried out the first recorded experimental study on humans

TTTTT

16. The following statements are true about the history of epidemiology

James Lind discovered the prevention of scurvy
Captain John Graunt analyzed the bills of mortality
Robert Koch is considered the father of bacteriology
Ignaz Philip Semmelweis suggested hand-washing to avoid obstetric infection
Percival Pott associated lung cancer to chimney soot

TTTTT

17. The following statements are true about the history of epidemiology

William Farr started the discipline of vital statistics

Joseph Lister introduced antiseptic surgery

Epidemiology started as a study of epidemics
The prophet taught the necessity of quarantine in cases of plague
Omar Ibn al Khattab entered Syria despite being told there was a plague epidemic

TTTTF

18. The following statements are true about the history of epidemiology

Zahrawi was the first to accurately describe the contagiousness of measles
Abubakr al Razi described the contagiousness of smallpox
Abubakar al Razi did not do any work on measles
Edward Jenner discovered variolation
John Snow discovered that the London cholera epidemic was related to polluted water
Robert Koch discovered the cause of tuberculosis

FTFFTT

19. The following statements are true about the history of epidemiology

Louis Pasteur discovered that the tubercle bacillus caused tuberculosis
Edward Jenner introduced vaccination against measles in children
John Snow discovered the cholera virus
Robert Koch discovered the anthrax bacillus
Robert Koch discovered the cholera bacterium

FFFTT

20. The following statements are true about ethico-legal issues in epidemiology

Observational epidemiological studies do not require approval by an ethics committee
Informed consent is not necessary in epidemiological studies by honest physicians
Privacy and confidentiality can be ignored if the subjects of research are children
Epidemiologists are not bound to explain their findings to the public
Epidemiological evidence is not admissible in courts of law

FFFFF

EXERCISES: COMPUTATIONS

EXERCISES: JOURNAL STUDY

Using the internet or the on-line journal data base identify and summarize

1. A journal articles on the history of epidemiology

2. A journal articles on the role of epidemiology in modern disease control

3. Roles and activities of one epidemiological professional association

4. Roles of epidemiology units in the Ministry of Health

EXERCISES: PRACTICAL ASSIGNMENTS

1. Prepare a short questionnaire with the definition of epidemiology, its methods, and its roles in public health and administer it to a group of final year medical students, medical officers, and nurses. The aim of the questionnaire is to determine the level of epidemiological awareness. Summarize and discuss your findings.

2. Pick any of your medical textbooks and determine how many use the term ‘epidemiology’ in their index.

3. Contact the Pahang State Epidemiology Unit or the Kuantan District Epidemiology Unit and list their activities

UNIT 1.2

INTRODUCTION TO CLINICAL EPIDEMIOLOGY

Learning Objectives

· Clinical epidemiology: definition , scope, and roles

· Historical development of clinical medicine

· Use of clinical epidemiology techniques in diagnosis, treatment, and prognosis

Key Words and Terms

· Clinical competence

· Clinical databases

· Clinical decision making

· Clinical medicine

· Clinical protocols

· Clinical, Good clinical practice (GCP)

· Disease, diagnosis of disease

· Disease, management of disease

· Disease, Natural history of disease

· Disease, Prognosis of disease

· Disease, treatment of disease

· End-point

· Medicine, evidence-based medicine

· Medicine, experimental medicine

· Medicine, history of medicine

· Prognostic factors

· RCT (randomized controlled clinical trial)

· Survival, mean survival

· Survival, median survival

· Therapeutic trials

· Treatment, effectiveness of treatment

· Treatment, efficacy of treatment

· Treatment, failure of treatment

· Treatment, treatment compliance

UNIT SYNOPSIS

1.2.1 DEFINITIONS, SCOPE, and ROLES

Clinical epidemiology is defined as study of outcome of disease and the factors that affect the variation in outcome. It applies epidemiological methodology to patient care. The ‘exposures’ are therapy and the etiological factor. The ‘outcomes’ are disease progression, disease complications, and mortality. The scope of clinical epidemiology covers definition of abnormality, diagnosis (symptoms, signs, and diagnostic procedures), frequency, risk, prognosis, treatment, and prevention. It also involves study of the natural history of disease, study of the sensitivity, specificity, and predictive value of diagnostic and screening tests; study of therapy using randomized clinical trials. It also studies treatment efficacy, and effectiveness. It is used in the investigation of disease etiology, identification of risks, identifying syndromes, classifying diseases, differential diagnosis, planning and follow-up of treatment. The conceptual basis and methodology of clinical epidemiology are the same as those of general population-based epidemiology.

1.2.2 HISTORICAL EVOLUTION OF CLINICAL MEDICINE

In Pre-historic times magic and superstition were mixed with medical care and were closely related to the prevailing belief systems. Mesopotamian medicine was magico-religious with priests serving also as physicians. Divination was used beside treatment with vegetables, animals, and minerals. Early Egyptian medicine was mystical and priestly. Pills, potions, suppositories, purgatives, enemas, emetics, inhalants, and ointments were used. Egyptians knew circumcision, plaster for closing wounds, cautery for hemostasis, and incision & drainage for abscesses. Chinese medicine can be traced back to Fu Hse in about 3322BC. Traditional Indian Medicine knew the diseases of tuberculosis, cancer, diabetes mellitus, leprosy, and smallpox. Diagnoses were made by listening to the breath sounds, observing the color of eyes, the tongue, and the skin; feeling the pulse; tasting the sweetness of urine. Stress was put on diet, hygiene, and mental preparation. Herbs were used. Rauwolfia serpentina and opium were used as drugs. Indians knew excision, suturing, drainage, cauterization, laparatomy, removal of bladder stones, repair of fistulae, cesarean section, and cataract removal. The ancient Indian medicine is what has grown into Ayurdevic medicine of India today. Greek medicine benefited by learning from Asia Minor, Mesopotamia, and Egypt. It was closely related to religions and the temples. The main figures of Greco-Roman medicine were Hippocrates, Galen, and Aristotle. Normal physiology, disease, and treatment were based on the concepts of the 4 humors (blood, phlegm, yellow bile, and black bile), the 4 elements (earth, air, fire, and water), and the 4 qualities (hot vs. cold and wet vs. dry). Rest and diet were used in treatment. With the death of Galen in 199 BC Greco-Roman medicine entered its dark ages. Aulius Cornelius Celsius formulated the 4 cardinal signs of inflammation: pain, redness, heat, and swelling. Romans made practical but no theoretical contributions to the development of medicine. Muslim medicine started with translations. Nestorians had translated Greek medical works into Syriac. Muslims translated these Greek works into Arabic. They in addition made their own observations and discoveries. Abubakar al Razi described measles and wrote al Hawi. Ibn Sina wrote al Qanun fi al Tibb. Zahrawi wrote on surgery. European medicine in the Middle Ages was in general decay. The Christian Church contributed to lack of scientific growth. Superstition became wide spread. Muslim medicine was transferred to Europe through Andalusia (modern Spain) and Sicily in Italy creating the medieval medical reawakening (800-1500 CE). As a result of contacts with Muslims, the Salermo medical school emerged in Southern Italy in the 9^th century CE. Muslim medical writings were translated into Latin by Constantine Africanus (1010-1087 CE) at Salermo. Muslim works were expanded and annotated by Europeans and were taught at Universities in Bologne and elsewhere. The Renaissance (1500-1700 CE) was a period of the rise of anatomical knowledge. Besides translations of Muslim writings, Europeans undertook human dissections. Following the renaissance rapid developments were mad in physiology, microbiology, Pathology, and Pharmacology by use of empirical research. In clinical sciences, internal medicine lagged behind surgery. In 1636 CE clinical teaching of medicine started at Leyden. Schools of medicine developed in the 18^th century in London, Vienna, Paris, Edinburgh, and Dublin. The industrial revolution witnessed building of new hospitals. Modern medicine (20^th century CE onwards) has three distinguishing characteristics. It is evidence-based medicine. It uses advanced technological interventions. It uses human experimentation extensively.

1.2.3 NATURAL HISTORY OF ILLNESS

Natural history is the course of disease in patients who are not receiving any therapy or intervention. Knowledge of the natural history is necessary for planning rational treatment strategies. The stages of disease on the basis of clinical manifestation are: essentially normal (low risk), Establishment of disease-causing agent, appearance of signs, appearance of symptoms, disability, and death.

1.2.4 CLINICAL EPIDEMIOLOGY IN DIAGNOSIS

Disease is anatomical, biochemical, physiologic or psychological derangement. Clinical diagnosis is an effort to recognize the class or group to which a person's illness belongs. Epidemiology as the study of the distribution and determinants of disease provides background information needed in clinical diagnosis. Statistical abnormality, used to define disease, is defined as deviation beyond 2 standard deviations. The most often used strategy in clinical diagnosis is the hypothetico-deductive in which a hypothesis is formed from early clues and then history, clinical examination, and diagnostic tests are undertaken to confirm or reject the hypotheses. Epidemiological knowledge provides prior probabilities for clinical decision making. The clinician combines his empirical findings with the prior probabilities top reach a diagnosis. This may be informal or formal using Bayesian techniques. In formal clinical decision making, the problem is defined. Alternative actions and possible outcomes are determined. Probabilities are determined on the decision tree and the value of the outcome is computed. Diagnostic tests are used for assessing severity, predicting prognosis, estimating likely response to treatment, and to determine the actual response to treatment. The precision of each test, its sensitivity and specificity must be taken into consideration in interpreting its findings. Diagnostic procedures can be evaluated by computing their predictive value. Epidemiological parameters are used to choose a diagnostic procedure. Diagnostic tests are also useful in predicting illness outcome. Random controlled trials, follow up and case control study designs can be used to assess the role of diagnostic tests in predicting outcome. A hospital stores a lot of clinical data about patients. This data may be shared with other hospitals using local area net-works (LAN). Data-bases have been developed with AI capabilities and they can provide much support to the physician who is trying to diagnose a disease. This is done by comparison of the patient's data with several profiles stored in the data-base.

1.2.5 CLINICAL EPIDEMIOLOGY IN TREATMENT and PROGNOSIS

The objective of treatment must be identified: cure vs. palliation. The specific treatment modalities to be used must then be selected. Treatment targets must then be decided: dose, frequency, start, and end. Treatment decisions are based on clinical experience or medical literature. Formal decision analysis techniques using prior probabilities from clinical epidemiological studies can be used. Decision trees are used with decision nodes employing probabilities are from empirical data. Epidemiological measures of treatment are efficacy, effectiveness, safety, incidence of side effects, incidence of treatment failure, compliance, and functional status. The clinical data base can be used to predict patient compliance. Functional status is measured using: restricted activity days, workless days, bed-disability days. Clinical practice guidelines have been developed for many conditions. They are based on results of clinical trials and epidemiologic studies. The guidelines can be evaluated using specific criteria. Both randomized and non-randomized clinical trials are used in studying treatment efficacy. Therapeutic safety can be measured using case control, follow up, and case reports. Two main issues arise: characterization of patients who receive a particular treatment and ascertainment of unintended effects. Prognosis can be based on clinical experience or expert opinion and review of literature. Prognosis can also be assessed by comparing the patient's profile to the information in the clinical data-base

1.2.5 CLINICAL TRIALS ON HUMANS

Therapeutic clinical trials are controlled experiments to compare the effectiveness of different treatments by random allocation of study participants to treatment and control groups, observing the outcome of interest, and at the same time studying time-varying potential confounding variables. Trials can also be designed to be intervention or preventive trials. They may be accrual or non-accrual. Unadjusted censoring causes bias. Random allocation prevents selection bias. Double blinding prevents observer bias. The primary objective of drug clinical trials is efficacy and the secondary objective is assessing ADR. Complete randomization is simple but requires a large sample size. Stratified randomization balances prognostic factors. The trial can use historical, concurrent, self, untreated, placebo, negative, or positive controls. Clinical trials are preceded by screening in vivo in animals and in vitro in human tissues. Phase 1 trials study maximum tolerated doses, drug administration schedules, drug toxicity, and evidence of anti-tumor activity. Phase 2 studies assess therapeutic activity of a drug in advanced disease. Phase 3 trials are compare a drug to a placebo or a new drug to an existing drug. Comparability is assured by randomization and equal handling of the 2 groups. Phase 4 studies involve post-marketing surveillance by collecting data on short term and long term effects. Clinical trials on humans have several ethico-legal considerations. Search for better treatment justifies clinical trials. The ethical issues of trials are withholding a potentially beneficial treatment from the controls, unknown risks of new agents, lack of informed consent or consent under stress, trials if an effective treatment exists, trial when one treatment is known to be better, testing with no evidence of usefulness, unscientific research, violation of the normal doctor-patient relation, randomization when there is prior knowledge that one treatment is the better one, and failure to stop the study when harmful/beneficial effects appear.

UNIT OUTLINE

1.2.1 DEFINITIONS, SCOPE, and ROLES

A. Definition

B. Scope

C. Role/uses of clinical epidemiology.

D. Conceptual basis

E. Methodological basis

1.2.2 HISTORICAL EVOLUTION OF CLINICAL MEDICINE

A. Ancient medicine

B. Greek and roman medicine

C. Muslim medicine

D. European medicine

E. Modern medicine (20^th century onwards)

1.2.3 CLINICAL EPIDEMIOLOGY IN DIAGNOSIS

A. Natural History of Illness

B. Definition of disease and abnormality

C. Clinical assessment

D. Diagnostic tests

E. Clinical decision making and clinical data bases

1.2.4 CLINICAL EPIDEMIOLOGY IN TREATMENT

A. Strategy of treatment

B. Choice of treatment modality

C. Epidemiological measures of treatment

D. Epidemiological study designs for measuring safety

E. Clinical epidemiology in prognosis

1.2.5 CLINICAL TRIALS ON HUMANS

A. Historical Background

B. Definition and Purposes Of Drug Clinical Trials

C. Essential Elements Of Controlled Clinical Trials

D. Steps In Testing New Drugs

E. Ethico-legal Considerations

1.2.1 DEFINITIONS, SCOPE, and ROLES

A. DEFINITION

Clinical epidemiology is defined as study of outcome of disease and the factors that affect the variation in outcome. Clinical epidemiology is application of the epidemiological methodology to day to day patient care. It uses the same tools and methods as general epidemiology. Both randomized and non-randomized studies are used to study treatment outcome. In clinical epidemiology the ‘exposures’ are therapy and the etiological factor. The ‘outcomes’ are disease progression, disease complications, and mortality. Medicine is both an art and a science. Application of scientific principles in a clinical setting can improve the art of medicine. Clinical epidemiology applies epidemiological principles in clinical medicine to improve the diagnosis and management of disease. It is a bridge between epidemiology and clinical medicine.

B. SCOPE

The scope of clinical epidemiology covers inter alia: definition of abnormality, diagnosis (symptoms, signs, and diagnostic procedures), frequency, risk, prognosis, treatment, and prevention. The following types of studies are undertaken: (a) study of the natural history of disease using cohort or case control studies. (b) Study of the sensitivity, specificity, and predictive value of diagnostic and screening tests. (c) Study of therapy using randomized clinical trials. Epidemiological information is needed for making decisions on the following aspects of health programs: efficacy, effectiveness, compliance, quality assurance, planning, programming, monitoring, evaluation, and community diagnosis.

In defining abnormality we need to answer the questions whether the person is sick or well. This involves subjective psychological factors. Persons who have serious pathological lesions may not e aware of them or if aware may not be bothered. On the other hand there are many people who have no pathological lesions but are so anxious and worried that they come to the physician. It is important to establish the event or reasons behind seeking care because they may not be related in a direct way to the pathological lesions. The concern with defining risk is to evaluate how its contribution to disease and the effect of its removal or alteration. Diagnosis involves review of physical findings and laboratory data and an assessment of the diagnostic tests. The costs and risks of the tests must be considered before deciding to use them. In deciding in treatment, the objective must be determined. In some cases we may aim at complete elimination of the pathological lesion. In some other cases the aim of treatment intervention is palliative. For serious terminal illness consideration should be given to giving no treatment at all because it may make no difference but cause more suffering or impose psychological and financial burdens. All treatment options must be considered and the most appropriate is chosen. Prognosis seeks to foretell the future clinical progress of the disease which may lead to decisions of what treatments to institute or what treatments to stop. It also considers the short-term and long-term consequences of having the disease in question.

C. ROLE/USES OF CLINICAL EPIDEMIOLOGY.

Clinical epidemiology is used in the investigation of disease etiology, identification of risks, identification of syndromes, classification of diseases, differential diagnosis, planning and follow up of treatment. In both clinical practice and clinical trials, clinical epidemiology helps in the quantitative interpretation of diagnostic and screening tests.

D. CONCEPTUAL BASIS

Clinical epidemiology is based on the same concepts as were described for population epidemiology.

E. METHODOLOGICAL BASIS

Clinical epidemiology uses the same methodology as population epidemiology with a few modifications to suit the captive and limited clinical population.

1.2.2 HISTORICAL EVOLUTION OF CLINICAL MEDICINE

A. ANCIENT MEDICINE

In Pre-historic times humans tried to understand the causes of disease and tried to find cures for them. Often magic and superstitions were mixed with medical care and were closely related to the prevailing belief systems.

Much is known about Mesopotamian medicine from cuneiform texts. It was magico-religious with priests serving also as physicians. Divination was used. The materia medica contained vegetables, animals, and minerals. However no texts were found on surgical procedures. Sumerians practiced magical and priestly medicine. Babylonians inherited Sumerian customs and knowledge. Babylonian medicine was in the hands of priests. Their surgeons were slaves of physicians. Babylonian astrology had an impact on the practice of medicine. They believed that the destiny of man was determined by the movement of stars. They believed that blood carried all vital functions. The liver was considered an essential organ. In their writings they mentioned apoplexy, fevers, phthisis, plague, ENT diseases, eye diseases, rheumatism, tumors, abscesses, diseases of the heart, venereal diseases. They thought that toothache was due to gnawing of a worm. Hammurabi defined professional responsibilities of physicians and severe penalties were set for morbidity and mortality following surgical operations. Hammurabi’s codes contain the earliest mention of medical ethics.

Early Egyptian medicine was mystical and priestly. Imotep was a grand vizier and priest but at the same time a magician-physician. He instituted a medical cult as early as 2750 BC. By 525 BC he was worshipped as a deity. A papyrus discovered at Luxor in 1862 CE and written in 1700 BC summarized Imotep’s writings about paralysis of the bladder and intestines due to spinal lesions. Imotep's medical teachings were recorded in another papyrus written in 1553-1550 BC. Egyptians knew about the human body from their practice of embalming the dead into mummies but they did not develop a systematic knowledge of anatomy. Papyri contain mention of drugs in the form of pills, potions, suppositories, purgatives, enemas, emetics, inhalants, and ointments. In the field of surgery Egyptians knew circumcision, plaster for closing wounds, cautery to achieve hemostasis, and incision & drainage for abscesses. They however did not prescribe diet as a treatment.

Chinese medicine can be traced back to Fu Hse in about 3322BC.

Traditional Indian Medicine and surgery was developed. Vedic practice written from the 2^nd millennium BC used charms to control demons. In the period 800BC – 1000 AD Brahmanian medicine predominated and the following diseases were described: tuberculosis, cancer, diabetes mellitus, leprosy, and smallpox. Diagnoses were made by listening to the breath sounds, observing the color of eyes, the tongue, and the skin; feeling the pulse; tasting the sweetness of urine. Stress was put on diet, hygiene, and mental preparation. Herbs were used. Rauwolfia serpentina and opium were used as drugs. The following surgical operations were known: excision, suturing, drainage, cauterization, laparatomy, removal of bladder stones, repair of fistulae, cesarean section, and cataract removal. The ancient Indian medicine is what has grown into Ayurdevic medicine of India today.

B. GREEK and ROMAN MEDICINE

The Greeks learned from Asia Minor, Mesopotamia, and Egypt. Greeks made contributions to anatomy, physiology, and pathology. A lot of modern medical nomenclature is from the Greeks. Many medical traditions were inherited from the Greeks. Greek medicine was closely related to religions and the temples. Asklepos a physician became a cult and was worshipped. The major figures of Greco-Roman medicine were Hippocrates, Galen, and Aristotle.

The Hippocratic corpus, a collection of textbooks, lectures, and works by various authors, contains the earliest Greek writings on medicine and includes elements even before Hippocrates. After 300 BC the Hippocratic collection consisted of Hippocratic medicine, and teachings of the Sicilian, Athenian, Alexandrian, Persian, and Indian schools of medicine. Hippocratic medicine had Minoan, Mesopotamian, Egyptian, and Ionian sources. Its main contribution to medicine was that it was experiential. After years of medical decline, the renaissance of medicine started with the rediscovery of Hippocratic traditions of careful observation, recording, and inference. Actual clinical cases were described. Hippocratic physicians placed a lot of emphasis on the 4 humors. Rest was the most applied method of treatment. Great emphasis was also put on diet.

Aristotle (384-322 BC), a student of Plato and a teacher of Alexander the Great, wrote many biological works. He is credited with founding the discipline of comparative anatomy but he did not dissect humans. His philosophy had an impact on medicine for 2000 years. He taught the 4 qualities of hot vs. cold and wet vs. dry. He taught the 4 element of earth, air, fire, and water. To these were added the Hippocratic humors of blood, phlegm, yellow bile, and black bile.

Galen (129-199 CE) wrote on anatomy, physiology, and compiled earlier writings. Later authors copied or abstracted his writings. Galen’s writings can be considered as the synthesis of all ancient medical knowledge. He described bones, muscles, the brain, vessels but many of his physiological ideas were wrong. With his death in 199 BC Greco-Roman medicine entered its dark ages.

De Medica was written in about 30 CE by Aulius Cornelius Celsius as a compilation of previous writings. It formulated the 4 cardinal signs of inflammation: pain, redness, heat, and swelling and described various surgical operations.

By the 6^th century BC Greek medical schools were operating in Cos (where Hippocrates was born) and Cnidos. The Alexandrian school was established in about 300 BC and became famous in anatomy and physiology. Human dissection was undertaken. With the absorption of Alexandria into the Roman Empire, the medical school continued for centuries but with restricted activity and lack of originality.

Romans made practical but no theoretical contributions to the development of medicine. The Roman Empire did not produce great physicians. Rome became a center of medical teaching after the reign of Emperor Vespassan (70-79 CE). Medical schools in Rome and other parts of the empire were mainly for training army surgeons. Romans organized medical services, sanitation, aqueducts, public latrines, and food supplies. Public physicians were appointed to various towns. They organized general and military hospitals. The Church preserved medical knowledge during the Byzantine Empire.

C. MUSLIM MEDICINE

Nestorians had translated Greek medical works into the Syriac language. Muslims translated these Greek works into the Arabic language. They in addition made their own observations and discoveries. Abubakar al Razi described measles and wrote al Hawi. Ibn Sina wrote al Qanun fi al Tibb. Zahrawi wrote on surgery.

D. EUROPEAN MEDICINE

THE MIDDLE AGES

The middle ages were a period of general decay with the Christian Church being a major contributor to lack of scientific growth. The negative role of the Church became more intense ever since Christianity became the state religion of the Roman Empire. During the Middle Ages superstition became wide spread. Muslim medicine was transferred to Europe through Andalusia (modern Spain) and Sicily in Italy creating the medieval medical reawakening (800-1500 CE). As a result of contacts with Muslims, the Salermo medical school emerged in Southern Italy in the 9^th century CE. Muslim medical writings were translated into Latin by Constantine Africanus (1010-1087 CE) at Salermo. Muslim works were expanded and annotated by Europeans and were taught at Universities in Bologne and elsewhere.

DEVELOPMENT OF BASIC MEDICAL SCIENCES

Anatomy: The Renaissance (1500-1700 CE) was a period of the rise of anatomical knowledge. Besides translations of Muslim writings, Europeans undertook human dissections and disproved many of Galen’s teachings. Leonardo Da Vinci (1452 – 1519 CE) dissected human bodies and produced anatomical drawings. Andreas Vesalius (1514-1564 CE) made contributions to anatomy through his dissections and published De Humanis Corporis Fabrica in 1543 CE rejecting many of Galen’s ideas. Renaissance anatomists extended anatomical knowledge of the brain and the nervous system: Leonardo da Vinci (1452 – 1519 CE), Jacopo Beranganio de Capi (d. 1550 CE), Johannes Dryander (1500-1560 CE), Charles Etienne (1503-1564 CE), Andreas Vesalius (1514-1564 CE), Bartolommeo Eustachi (1520-1574 CE), Constanzio Verolio (1543-1578 CE). Further work on the nervous system and neurology was done in the 17^th century CE by Thomas Willis (1621-1675 CE) and Raymond Vieussans (1641-1715 CE). Contributions to anatomical knowledge of the nervous system were made in the 18^th century CE by Jakob Benignus Winslow (1669-1760 CE), Samuel Thomas Von Soemmering (1755-1830 CE), Munro ( ), and Antonio Scarpa (1747-1832 CE), Johannes Evangelista Purkinje (1787-1869) who described nerve cells, Heinrich Wilhem Gottfried Waldayer-Hertz (1836-1921 CE) proposed the neuron theory, Wilhem His (1831-1904 CE) described the axon, Camelio Golgi (1843-1826 CE) described the Golgi apparatus. Gaspare Melli (1581-1626 CE) discovered lacteals that carry lymph. Jean Pecquet (1622-1674 CE) discovered the thoracic duct. Marcello Malphighi (1628-1694 CE) described capillaries. Better knowledge of anatomy led to better surgery and surgery rose from a despised profession of barbers to a position of respect. In 1665 CE Robert Hooke (1635-1707 CE) published Micrographia in which he described cells. John Hunter collected many anatomical specimens.

Physiology: Santorio Santorio (1561-1636 CE) measured the pulse rate, discovered the thermometer, and carried out experiments on metabolism. William Harvey (1578-1652 CE) described blood circulation in 1628 CE but Ibn Nafis (1210-1288 CE) had discovered blood circulation much earlier but his views were not known in Europe. The 17^th -18^th centuries CE witnessed the rise of physiology. Robert Boyle (1627-1691 CE), the father of chemistry, published The Skeptical Chymist in 1661 and by then alchemy had become chemistry. Jean Baptiste Von Helmont (1577-1644 CE) was the father of chemical physiology. Albrecht Von Haller (1708-1777 CE) published books on physiology covering various issues. Sir Charles Bell (1774-1842 CE) studied the nervous system. Rene Antoine Ferchault Reamur (1683-1757 CE) studied gastric juices. These studies were extended by Abbate Lazaro Spallanzani (1729-1799 CE). William Prout (1785-1850 CE) demonstrated hydrochloric acid in the stomach. William Beaumont (1785-1853) studied gastric digestion in a wounded man with an open wound. Emil de Bois Reymond showed that a nervous impulse was accompanied by change of electrical potential. In 1771 CE Joseph Priestly (1733-1804 CE) discovered oxygen. Antoine Laurent Lavoisier (1743-1794 CE) discovered combustion and explained respiration. Edward Frederick Wilhelm Pflinger (1829-1910 CE) showed that chemical reactions of respiration took place in the lungs. Tustus Von Liebig (1803 – 1873 CE) elucidated many chemical processes of life and first described the concepts that underlie the nitrogen and carbon cycles. Sir John Floyer (1649-1734 CE) invented the pulse watch. In 1761 CE, Leopold Auenbrugger (1722-1809 CE) introduced percussion. Rene Theophile Hyacinthe Laennec (1781-1826 CE) invented the stethoscope. Johannes Muller (1841-1858 CE), was a great physiologist who studied the electrical phenomena of nerves and was the teacher of Humann Ludwig Ferdinand Von Helmholtz (1821-1894 CE). Claude Bernard (1813-1878 CE) founded experimental medicine, studied liver glycogen and pancreatic juices, and introduced the concept of milieu interieur in 1857 CE. Karl Friedrich Wilhem Ludwig (1816-1895 CE) invented the kymograph and studied salivary glands and their innervations. Later physiologists were William Beaumont (1785-1853 CE), Ivan Pavlov (1849-1936 CE), Sir William Maddock Bayliss (1860-1924 CE), Ernest Henry Sterling (1866-1927 CE), and Walter Bradford Canon (1871-1945 CE).

Microbiology: However many erroneous Greek concepts of disease persisted. Fracastoros (1478-1553 CE) developed ideas on infectious disease. Antoni Leeuwenhoek (1635-1723 CE) saw micro organisms under the microscope.

Pathology: The 19^th century witnessed the rise of pathology. Percival Potts (1714-1788) described Pott’s fracture, Pott’s disease, congenital hernia, and occupational cancer in chimney sweeps.

Pharmacology: In the era of reformation, herbal remedies became popular as botanical knowledge expanded. Mercury was used to treat syphilis.

DEVELOPMENT OF CLINICAL SCIENCES

Internal medicine: Internal medicine lagged behind surgery for a long time. De Bailbou (1538-1616 CE) described whooping cough. Thomas Syndenham (1624-1689), considered the father of modern medicine, published Methodus Curandi Febres (The Method of Treating Fevers) in 1666 CE. Bleeding using leeches was a common treatment in the 18^th century CE.

Obstetrics and Gynecology: Peter Chamberlain (d. 1631 CE) discovered the obstetric forceps.

DEVELOPMENT OF MEDICAL EDUCATION

In 1636 CE clinical teaching of medicine started at Leyden. Schools of medicine developed in the 18^th century in Vienna, Paris, Edinburgh, and Dublin. In London clinical teaching was at Guy’s Hospital and St Thomas Hospital. Famous clinical teachers at Guy’s Hospital were Sir Aitley Pastor Cooper (1768-1841 CE), Richard Bright (1789-1858 CE), Thomas Addison (1798-1866 CE), and Thomas Hodgkins (1798-1866 CE).

HOSPITALS

The industrial revolution witnessed building of new hospitals.

E. MODERN MEDICINE (20^th century onwards)

HUMAN EXPERIMENTATION

Ibn Sina suggested clinical trials in his Qanun fi al Tibb including comparisons of 2 patients. Ambrose Pare (1510-1590) experimented with a new treatment for bullet wounds instead of the traditional method of using burning oil. In 1721 smallpox inoculation was tried in 21 convicts. In 1747 a comparative trial of lemon for cure of scurvy was carried out by James Lind (1716-1794). He selected 12 patients with scurvy who lay together and had the same diet. Two were given lemons and oranges daily. Two were given a quart of cider. Two were given vinegar and an elixir of vitriol. The rest were given nothing. After 6 days those who were given oranges were well enough to look after the other sick. The cider seemed to have some benefit. The other remedies were not beneficial. William Wuthering carried out a large study involving 163 subjects to investigate digitalis as a treatment for dropsy. Edward Jenner experimented with vaccination. Sir Austin Bradford Hill in 1946 carried out a trial of streptomycin in the treatment of pulmonary TB.

EVIDENCE-BASED MEDICINE

BIOTECHNOLOGY

1.2.3 CLINICAL EPIDEMIOLOGY IN DIAGNOSIS

A. NATURAL HISTORY OF ILLNESS

DEFINITION

Natural history is the course of disease in patients who are not receiving any therapy or intervention. Knowledge of the natural history is necessary for planning rational treatment strategies. The study designs for measuring natural history are cohort and case control. The case control study compares those with an outcome to those without the outcome for symptoms and signs of disease. Interpretation of studies of natural history is complicated by individual variations that make generalizations difficult.

STAGES OF DISEASE ON THE BASIS OF CLINICAL MANIFESTATION

Essentially normal (low risk)

Establishment of disease-causing agent

Appearance of signs

Appearance of symptoms

Disability

Death

STAGES OF NATURAL HISTORY: ON BASIS OF PATHOGENESIS

STUDY DESIGNS FOR STUDYING NATURAL HISTORY

B. DEFINITION OF DISEASE and ABNORMALITY

DISEASE

EPIDEMIOLOGICAL CRITERIA OF ABNORMALITY

Statistical abnormality is defined as deviation beyond 2 standard deviations. It may also be defined in terms of percentiles. A condition that is regularly associated with disease or disability is considered an abnormality. In the definition of abnormality there is an underlying assumption that it is treatable. There is no point in regarding a condition abnormal if nothing can be done about it. The most often used strategy in clinical diagnosis is the hypothetico-deductive in which a hypothesis is formed from early clues and then history, clinical examination, and diagnostic tests are undertaken to confirm or reject the hypotheses.

C. CLINICAL ASSESSMENT

Clinical assessment is a very powerful tool. Two clinical examiners could disagree for the following reasons: differences in the senses like touch, differences in interpretation, or just sheer incompetence. Epidemiological knowledge provides prior probabilities for clinical decision making. The clinical combines his empirical findings with the prior probabilities top reach a diagnosis. This may be informal or formal using Bayesian techniques. In formal clinical decision making, the problem is defined. Alternative actions and possible outcomes are determined. Probabilities are determined on the decision tree and the value of the outcome is computed. Sensitivity analysis is then used to evaluate the decision.

D. DIAGNOSTIC TESTS

Diagnostic tests are used for: assessing severity, predicting prognosis, estimating likely response to treatment, and to determine the actual response to treatment. The definition of what is normal in tests must be very clear. The precision of each test, its sensitivity and specificity must be taken into consideration in interpreting its findings. Diagnostic procedures can be evaluated using: PV+, PV-, decision tree methods, Bayes' theorem, and the likelihood ratio method. Epidemiological parameters are used to choose a diagnostic procedure. Diagnostic tests are also useful in predicting illness outcome. Random controlled trials, follow up and case control study designs can be used to assess the role of diagnostic tests in predicting outcome.

E. CLINICAL DECISION MAKING AND CLINICAL DATA BASES

CLINICAL DATA-BASES

A hospital stores a lot of clinical data about patients. This data may be shared with other hospitals using local area net-works (LAN). Data-bases have been developed with AI capabilities and they can provide much support to the physician who is trying to diagnose a disease. This is done by comparison of the patient's data with several profiles stored in the data-base.

1.2.4 CLINICAL EPIDEMIOLOGY IN TREATMENT and PROGNOSIS

A. STRATEGY OF TREATMENT

B. CHOICE OF TREATMENT MODALITY

Treatment decisions are based on clinical experience or medical literature. Formal decision analysis techniques using prior probabilities from clinical epidemiological studies can be used. Decision trees are used with decision nodes. The probabilities are from empirical data. Epidemiological methodology can also be used to study patient compliance, formulate guidelines to treatment, and study side effects of treatment.

C. EPIDEMIOLOGICAL MEASURES OF TREATMENT

Epidemiological measures of treatment are efficacy, effectiveness, safety, incidence of side effects, incidence of treatment failure, compliance, and functional status. Efficacy is … Effectiveness is …. Incidence rates can be computed for several events: side effects, adverse drug reactions, and treatment failure. The clinical data base can be used to predict patient compliance. Functional status is measured using: restricted activity days, work loss days, bed-disability days. Clinical practice guidelines have been developed for many conditions. They are based on results of clinical trials and epidemiologic studies. The guidelines can be evaluated using specific criteria.

D. EPIDEMILOGICAL STUDIES OF TREATMENT EFFICACY

Random controlled trials for measuring treatment or therapeutic efficacy. A common problem with such studies is non-compliance. Non-compliant patients should still be analyzed as part of the group to which they were allocated. Endpoints may also be difficult to measure and in some cases we may have to resort to antecedents of end-points. Sufficient time must be allowed for that treatment to have an effect before its efficacy is measured. Randomized trials are expensive.

Non-randomized trials for measuring treatment efficacy have the disadvantage of bias. The following types of non-randomized trials may be used: comparing non concurrent population groups, case control studies, follow up studies, and case reports.

E. EPIDEMIOLOGICAL STUDY DESIGNS FOR MEASURING SAFETY

Therapeutic safety can be measured using case control, follow up, and case reports. Two main issues arise: characterization of patients who receive a particular treatment and ascertainment of unintended effects.

F. CLINICAL EPIDEMIOLOGY IN PROGNOSIS

Prognosis can be based on clinical experience or expert opinion and review of literature.

Prognosis can also be assessed by comparing the patient's profile to the information in the clinical data-base

1.2.5 CLINICAL TRIALS ON HUMANS

A. HISTORICAL BACKGROUND

Louis PCA (1836) undertook a clinical trial in which he demonstrated that delaying blood letting reduced pneumonia mortality (quoted by Don McNeil in Epidemiological Research Methods, Wiley & Sons New York 1996, page 1). An early trial of streptomycin in treatment of tuberculosis was carried out by Bradford Hill in 1945.

B. DEFINITION and PURPOSES

DEFINITION

Clinical trials are controlled experiments to compare the effectiveness of different interventions. They are classified as therapeutic, intervention, or preventive. Therapeutic trials involve treatments or procedures that include chemotherapy, surgery, radiotherapy, and immunotherapy. Intervention trials involve relieving medical conditions such as use of anti-hypertensives for stroke. Preventive trials anticipate disease conditions and prevent them from occurring such as trials of BCG vaccination to prevent TB. Cessation experiments are a type of intervention. In accrual studies subjects are recruited in the course of the study. In non-accrual studies subjects are recruited before start of the study. Study participants are allocated randomly to 2 groups, the treatment group and the control. In some cases the total number is not fixed in advance. If randomization is not possible concurrent or historical controls can be used. More complex study designs can be used such as studies with more than 2 groups/arms, cross-over studies, stratified randomization, using the same subject and assessing pre- and post treatment status, and testing more than 2 treatments at the same time. The sizes of the experimental and comparison groups must be big enough to assure a study of sufficient power. For best results the two groups should be equal in size. Both groups are followed to observe the outcome of interest. At the same time information is collected on potential confounding variables that vary by time. Loss to follow-up by death or refusal to continue being in the study causes a phenomenon called censoring that can cause bias unless special statistical techniques are used to adjust for its effects. The study can be terminated early when serious ADR develops in one group or when a decisive advantage of the drug in the treated group is seen making the continued denial of effective treatment to the comparison group un-ethical. Clinical trials being experimental studies have two major advantages. Selection bias does not arise because of the random allocation. Observer bias can be removed by double blinding. The physician assessing treatment outcome does not know the treatment given. The patient does not know what treatment group he belongs to. The clinical trial suffers from three disadvantages. The design is complex. Ethical issues arise regarding informed consent. Clinical trials are expensive studies.

PURPOSES OF DRUG CLINICAL TRIALS

Aureolus Theophratus Bombastus rejected the views of Hippocrates and Galen and argued that disease has specific causes and could have specific chemical cures. This was one of the motivations for clinical trials to look for chemical cures. The primary objective of drug clinical trials is to test the efficacy of drugs. The drug trials may be therapeutic or prophylactic. The secondary objective of drug clinical trials is to assess toxicity, side-effects, and adverse drug reactions (ADR) of drugs. A clinical trial essentially compares a treatment to a control group.

The concept of therapeutic index is important in clinical trials. It is the relation of benefit to toxicity. Considerations of efficacy and toxicity are therefore both important in clinical trials.

C. ESSENTIAL ELEMENTS OF CONTROLLED CLINICAL TRIALS

The clinical trial has several essential elements: formulation of the hypothesis, definition of a trial population, definition of the event/outcome, definition of what constitutes a significant difference, determination of error rates (type 1 (alpha) is rate of false positive & Type 2 (beta) is rate of false negative, consideration of the hazard function, random assignment to treatment groups, unbiased assessment of response, and proper analysis of the data.

Consideration of the expected shape of the hazard/risk function is important for the design and interpretation of the study. The hazard may be high immediately after surgery but falls off with time giving greater prominence to competing causes of death. The patient is interested in the early stages of the hazard functions but physicians may be interested in 5-year survival. In some diseases like lung cancer, long term hazard has no meaning.

Concurrent comparison of procedures or treatments

There are three common types of biological experimentation: completely randomized, stratified randomization, crossover, and use of controls. Complete randomization has the advantage of being simple. It has the disadvantage of requiring larger sample sizes because it has more heterogeneity among its members. The stratified design has the advantage of balancing prognostic factors. Controls may be historical or concurrent. They may be self controls, untreated controls, or placebo controls. A control may be described as negative when there is no response expected and only background effects are being studied. An active control has a response.

There are three approaches to controlling for confounding in randomized studies. The study may be confined to one level of the confounder. Matching may be used. Adjustment may be carried out at the analysis stage in 3 ways: using standardized rates for both the treated and the untreated, MH adjustment, and multivariate analysis.

D. STEPS IN TESTING NEW DRUGS

The screening process is long and systematic but could give false positives and false negatives. A synthetic drug is selected based on some rational criteria. It is screened by in vivo tests in rats or in vitro tests on human tissues before it is tested in animals.

Animal tests: The first stage is to screen drugs using animal tests to reject inactive preparations. There are no formal design requirements at this stage of the study. The design and approach depend on the intuition of the investigator.

Phase 1: Studies in humans start with the phase 1 clinical trials. These are small exploratory investigations that are not comparative. They accomplish 4 objectives: (a) determining the optimal or maximum tolerated dose, MTD. (b) studying drug administration schedules and (c) studying drug toxicity, qualitative and quantitative and (d) evidence of anti-tumor activity. In determining MTD, patients are entered at a given dose schedule. If they tolerate it, they are then put on a higher dose schedule until the limit of tolerance is reached. Patients selected for phase 1 trials have disseminated disease that is not amenable to treatment. Separate trials must be carried out for adults and children because of differences in drug kinetics. Trials for solid must be separated from those of non-solid tumors. Pregnant women are excluded. The patient must have life expectancy of at least 12 weeks. Animal data is used to decide the starting dose, dose schedule, and dose escalation.

Phase 2: Phase 2 studies are small non-comparative studies that assess therapeutic activity of a drug. The objective of phase 2 trials is to screen for anti-tumor activity in advanced disease. There are 2 sub-stages: stage 2a determines whether the drug is effective; stage 2b is a follow-up to determine a precise estimate of effectiveness. Phase 2 may be disease-oriented (test one drug on a given disease) or drug oriented (test several disease on a drug). Three designs are possible: single stage, sequential, and multi-stage (enter patients in batches). The end-points of a phase 2 trial are: response or toxicity. Efficacy is measured as the proportion of the number responding to the number treated; a cut-off of 0.2 or 0.3 is used for efficacy determination. False negative and false positive errors can occur. The sources of bias are: selection bias, wait and see attitude, and selective reporting of results. Controls may be used in phase 2 trials comparing the new agent against a standard agent. Stratification may be carried out. Cross-over designs are possible. Single or combination therapies are tested.

Phase 3: This is the main stage of clinical trials. It is a comparative clinical trial that compares two drug regimens or compares a drug regimen to a placebo. Its objective is to compare the new agent against existing agents by determining relative efficacy in a comparative trial. The trial specifically aims at (a) selecting the better treatment (b) obtaining a precise measure of the effectiveness of the treatment regimen. The following measures are taken to ensure comparability: (a) The 2 groups must be similar with the exception of the treatment being assessed. This is ensured by randomization (b) The 2 groups must be treated in exactly the same way. Double blind techniques are used to prevent the possibility of investigator bias. Phase 3 trials may be carried out for adjuvant therapies or for advanced disease. In adjuvant studies, the important end-points are remission duration (disease-free survival) but in advanced disease the end-point is survival until death. Adjuvant trials usually require a large number of subjects. A phase 3 study has three main stages: study design and protocol development, patient accrual and data collection, and follow up and analysis. Many types of specialized personnel are involved: study chairman, statistician, clinical research associates, and the data coordinator.

Phase 4: Phase 4 studies involve post-marketing surveillance by collecting data on short term and long term effects.

E. ETHICO-LEGAL CONSIDERATIONS

The medical profession is obliged to seek better ways of treating disease which justifies human experimentation. Inaction by the medical profession would be considered un-ethical

Treatments, even those widely used and widely accepted, must be continually re-evaluated for example high-dose estrogen for prostate cancer and clofibrate were widely used but later were found dangerous.

It is justifiable to subject a patient to experimentation if he can see hope in the trial: (a) present treatment is not effective (b) patient not responding to the standard treatment. The situation in which a superior treatment is sought when the current treatment is effective is more complicated ethically. Use of a placebo raises ethical issues because those in the control group are not deriving any benefit. It is probably acceptable in diseases like headache where it may have an effect or in adjuvant therapy.

There must be sufficient evidence of usefulness of the test material to justify subjecting half of the study population to its potential risks. The new treatment must be compared with the best available so far. It is unethical to compare the new treatment against an inferior existing treatment. An ethical issue also arises when a potentially useful treatment is withheld from one half of the study population.

Clinical research can be ethical only if it is scientific.

Informed consent interferes with the doctor-patient relation. It is difficult for a physician to tell a patient that he does not know which of the two treatments is better and at the same time warn against all the side effects expected. Informed consent does not however legalize a trial that is of no benefit to the patient. The following information must be given to the subject of the study before seeking consent: aims, methodology, duration, benefits, and foreseeable risks of the research. Possible costs should be explained to the subject. The treatment of research-related harms as well as compensation for that harm must be explained. The subject must be informed about possible advantageous alternatives so that they can choose to undergo treatment in the knowledge that they have the choice to choose the alternative. The subjects must be informed that they have the freedom to refuse participation and to withdraw at any stage of the research. They should be aware of the consequences of their decision to withdraw. Details about maintenance of confidentiality must also be explained. The subject should know how and when research findings will be communicated to him or her. The total number of research subjects must also be revealed. (page 380 John M Last Public Health and Human Ecology 2^nd edition Prentice Hall International, Inc.).

Randomization when there is prior knowledge that one treatment is better than another one

Patients under the stress of disease may not fully understand the study and therefore their consent is not free

Failure to stop the study when harmful/beneficial effects appear

ILLUSTRATIONS

EXERCISES: TRUE/FALSE QUESTIONS

1. The following statements are true about use of clinical epidemiology

Clinical epidemiology has a role in the diagnosis of disease
Clinical epidemiology has no role at all in prediction of prognosis
Bayesian probability is involved in clinical diagnosis
Hospital clinical data bases are useful to the physician in making a diagnosis
The hospital clinical data base can be used to predict patient compliance

TFTTT

2. The following statements are true about clinical epidemiology

Clinical epidemiology is not concerned with study of disease etiology
In clinical epidemiology, the treatment intervention is treated as the exposure
Disease progression is not considered an outcome in clinical epidemiology
Disease outcomes in clinical epidemiology include mortality
Disease complication is not a valid outcome in clinical epidemiology

FTFTF

3. The following statements are true about the scope of clinical epidemiology

Clinical epidemiology does not cover symptoms, signs, and diagnostic procedures
Clinical epidemiology never studies disease frequency
Treatment and prognosis are not part of clinical epidemiology
Disease prevention is a concern of clinical epidemiology
Clinical epidemiology does not study the natural history of disease

FFFTF

4. The following statements are true about the scope of clinical epidemiology

Clinical epidemiology studies the sensitivity of diagnostic tests
Clinical epidemiology is incapable of studying the specificity of diagnostic tests
Choice of a diagnostic test depends on its predictive value
Randomized clinical trials are used to compare different treatment interventions
Efficacy and effectiveness of treatments are studied by epidemiological methods

TFTTT

5. The following statements are true about the history of medicine

Medical practice in pre-historic times was mixed with magic and superstition
Priests served as physicians in ancient Mesopotamia
Hammurabi’s codes included elements of medical ethics
Ancient Egyptian medicine was scientific and had no magic or superstition
Ancient Egyptians knew about anatomy from embalming mummies

TTTFT

6. The following statements are true about the history of medicine

Chinese medicine can be traced back to Fu Hse in about 3322BC
Ancient Indian medicine is the forerunner of Ayurdevic medicine
Greeks learned some of their medicine from Mesopotamia and Egypt
Hippocrates is the father of modern European medicine
Aristotle contributed to philosophy and had no role in medicine

TTTTF

7. The following statements are true about Greco-Roman medicine

Greco-Roman medicine was closely related to religion and the temples
The 4 humors were blood, phlegm, yellow bile, and black bile
The 4 elements were earth, air, fire, and water
The 4 qualities were hot vs. cold and wet vs. dry
The theories of humors, elements, and qualities explain modern pathology
The theories of humors, elements, and qualities can explain modern physiology

TTTTFF

8. The following statements are true about Greco-Roman medicine

Rest and diet were used in treatment
Celsius formulated the 4 cardinal signs of inflammation
The cardinal signs of inflammation are: pain, redness, heat, and swelling
Romans made practical but no theoretical contributions to medicine
Galen was an important figure in Greco-Roman medicine
Greco-Roman medicine declined after 199 BC

TTTTTT

9. The following statements are true about Muslim medicine

Muslim medicine started with translations of Greek medical books
Muslim physicians copied and used Greek translations
Muslims made no observations or discoveries of their own
Ibn Sina’s book al Qanun fi al Tibb was taught in Europe until recent times
al Zahrawi work on surgery was translated and was used by Europeans

TTFTT

10. The following statements are true about European medicine

European medicine in the middle ages was in general decay
Muslim medicine reached Europe through Andalusia and Italy
Constantine Africanus translated Muslim medical writings into Latin
Europeans made no additions to the anatomical knowledge learned from Muslims
Modern medicine is evidence-based and relies on human experimentation

TTTFT

11. The following statements are true about the natural history of disease

Knowledge of natural history plays no part in disease treatment
Symptoms of disease appear long before signs
Entry of an agent in the body is always followed immediately by symptoms
All stages of disease natural history can be seen in patients who get no treatment
Disability and death are not part of the natural history of disease

FFFTF

12. The following statements are true about use of epidemiology in diagnosis

Disease is anatomical, biochemical, physiologic or psychological derangement
Disease can not be defined in statistical terms
The hypothetico-deductive approach is used in clinical diagnosis
Epidemiological knowledge is used in clinical decision making
Random controlled trials have no role in assessment of diagnostic tests

TFTTF

12. The following statements are true about use of epidemiology in treatment

Decision analysis techniques are not useful in choice of treatment modalities
Epidemiological techniques cannot be used to assess efficacy and effectiveness
Clinical data bases can be used to predict patient compliance
Clinical trials are useless in formulating clinical practice guidelines
Clinical trials are used in formulating clinical practice guidelines
Therapeutic safety cannot be measured using epidemiologic studies

FFTFTF

13. The following statements are true about clinical trials

A. Clinical trials are controlled experiments to compare different treatments

B. The primary objective of drug clinical trials is efficacy

C. A secondary objective of clinical trials is assessing Adverse drug reactions

D. Clinical trials employ random allocation of study participants

E. Random allocation makes the study balanced

F. Random allocation prevents selection bias.

TTTTTT

14. The following statements are true about clinical trials

A. Adjustment for time-varying confounding variables is impossible

B. Complete randomization is simple but requires a large sample size

C. Stratified randomization balances prognostic factors

D. Double blinding prevents observer bias.

E. Unadjusted censoring causes bias

FTTTT

15. The following statements are true about clinical trials

A. Historical controls are better than concurrent controls

B. Placebo controls are never used because of the cheating involved

C. A subject cannot serve as his/her own control

D. In vivo screening of new drugs in animals precedes human trials

E. Phase 1 trials study maximum tolerated doses and drug administration schedules

FFFTT

16. The following statements are true about clinical trials

A. Phase 1 trials study drug toxicity

B. Phase 2 trials assess therapeutic activity of a drug in advanced disease

C. Phase 3 trials are compare a drug to a placebo or a new drug to an existing drug

D. Phase 4 studies is pre-marketing surveillance

E. Post-marketing surveillance is collecting data on short term and long term effects.

F. Search for better treatment justifies clinical trials

TTTTTT

17. The following are ethical issues in clinical trials

A. Withholding a potentially beneficial treatment from the controls

B. New agents may have unknown risks

C. Lack of informed consent

D. Consent under stress

E. Undertaking trials if an effective treatment already exists

TTTTT

18. The following are ethical issues in clinical trials

A. Undertaking a trial when one treatment is known to be better

B. Testing a new drug with no evidence of usefulness

C. Testing a new drug using unscientific research

D. Violation of the normal doctor-patient relation

E. Randomization when there is prior knowledge that one treatment is the better one

F. Failure to stop the study when harmful/beneficial effects appear

TTTTTT

EXERCISES: COMPUTATIONS

EXERCISES: JOURNAL STUDY

Use the internet or the on-line journal data-base to identify and summarize

4. 1 Journal articles on the history of clinical epidemiology

5. Activities of one professional organization concerned with clinical epidemiology

6. 1 journal article on the role of clinical epidemiologists in the hospital setting

7. Role of Imotep in ancient Egyptian medicine

8. The Chinese physician Fu Hse in about 3322BC.

9. Surgical procedures carried out in ancient Indian medicine

10. Contributions of Hippocrates, Galen, Aristotle, and Celsius to Greco-Roman medicine

11. The Alexandrian medical school of Greco-Roman medicine

12. Ibn Sina’s contributions to medicine

13. Al Zahrawi’s contributions to surgery

14. Contributions to anatomy by Leonardo da Vinci (1452 – 1519 CE) and Andreas Vesalius (1514-1564 CE), and Bartolommeo Eustachi (1520-1574 CE), Constanzio Verolio (1543-1578 CE)

15. Contributions to anatomy of the nervous system by Thomas Willis (1621-1675 CE), Jakob Benignus Winslow (1669-1760 CE), Johannes Evangelista Purkinje (1787-1869), and Camelio Golgi (1843-1826 CE).

16. Contributions of the following to physiology: Santorio Santorio (1561-1636 CE), William Harvey (1578-1652 CE), Ibn Nafis (1210-1288 CE), William Beaumont (1785-1853), Rene Theophile Hyacinthe Laennec (1781-1826 CE) invented the stethoscope. Claude Bernard (1813-1878 CE), Ivan Pavlov (1849-1936 CE), Sir William Maddock Bayliss (1860-1924 CE), Ernest Henry Sterling (1866-1927 CE), and Walter Bradford Canon (1871-1945 CE).

14. Contributions of the following to microbiology: Fracastoros (1478-1553 CE) and Antoni Leeuwenhoek (1635-1723 CE)

15. Contributions of Percival Potts (1714-1788) to pathology and surgery

16. Contributions to internal medicine by Thomas Syndenham (1624-1689)

17. Contributions of Peter Chamberlain (d. 1631 CE) to obstetrics and gynecology

EXERCISES: PRACTICAL ASSIGNMENTS

1. Pick an elementary textbook of general epidemiology and another one of clinical epidemiology and compare their tables of contents.

2. Check in your local hospital whether any clinical epidemiological activities are undertaken

UNIT 1.3

INTRODUCTION TO PUBLIC and COMMUNITY HEALTH

Learning Objectives

· Definition, scope, strategies, and methods of public health

· Historical evolution of the public health movement

· Community health: definition and strategies

Key Words and Terms

· Community development

· Community diagnosis

· Community health

· Community medicine

· Community organization

· Community participation

· Disease prevention

· Environmental protection

· Evaluation

· Health promotion

· Health protection

· Health services, community health services

· Health services, personal health services

· Hygiene

· Medical services

· Preventive medicine

· Public health

· Public health intervention

· Public health surveillance

· Social medicine

· Social services

UNIT SYNOPSIS

1.3.1 DEFINITION OF PUBLIC HEALTH

Public health is the sum of all official (government) efforts to promote, protect, and maintain health. It is investigation, promotion, and evaluation of optimal health services for communities. Public health has 2 main paradigms: disease prevention & health promotion. Public health had developed as a reaction to bad health and social conditions and can therefore be looked as a reform movement. The scope of public health covers health problems and disease determinants. It faces many challenges because of its wide scope: demographic, globalization, human will and behavior, scarcity of resources, distributive justice & equity, and ethico-legal issues. The essential public health functions are: prevention of disease and injuries; protection against environmental hazards; promotion of healthy behavior; assurance of quality and accessibility of health services; and provision of personal and community health services. Public health uses the scientific approach to solve problems. However its interventions are often tentative and do not wait for acquisition of perfect information.

1.3.2 DISCIPLINES THAT ASSIST PUBLIC HEALTH

Quantitative disciplines that contribute to public health are epidemiology, biostatistics, and operations research. Economic disciplines deal with resources. Other disciplines that make contributions are sociology, social policy, communication, and management sciences.

1.3.3 PUBLIC HEALTH PROGRAMS and STRATEGIES

The main programs of public health are health policy formulation, disease prevention and health promotion, medical and social services, and environmental protection. The main strategies are surveillance, intervention, and evaluation. Economic interventions have a public health impact.

1.3.4 HISTORY OF PUBLIC HEALTH

In the UK government interest in public health was complacent and adhoc. The cholera epidemics of 1831-2 and 1865-66 as well as the 1842 Chadwick report on sanitary conditions and disease led to an awakening. The Public Health Act was passed in 1848. Legislation 1872 and 1875 established a sanitary authority in every district. Housing laws were passed in the 1870s. In 1872 local authorities were required to appoint a medical officer of health (MOH) for sanitation and disease control. In 1939 local authorities were permitted to provide a wider range of services including MCH. The National Health Service (NHS), established in 1948, became the main provider of services and in 1968 started providing primary health care through community physicians. In the US public health started with port health and quarantines. Higher disease than combat mortality in the American civil war led to an awakening. State and national health boards were set up by 1879. In 1912 the role of the United States Public Health Service (USPHS) was expanded to include investigation of disease and sanitation. In 1912 USPHS started helping states develop public health departments. The 1935 Social Security Act provided funds to states through USPHS for public health. After World War II funding of public health programs was seen as part of the defense policy. The political atmosphere of the 1950s did not support public health but during the Great Society (1960-1980) funding for public health increased and medicaid and medicare bills were passed in 1965. In the health promotion period (1980-1990) health promotion and disease prevention were recognized as priorities and the role of life-style change was emphasized. The major community health problems of the 1990s were: rising health care costs and barriers to access, environmental concerns, life style diseases (cancer, stroke, and injuries), communicable diseases (HIV, Lyme’s disease), abuse of alcohol and drugs

1.3.5 COMMUNITY HEALTH

Community Health involves both private and public efforts of individuals, groups, and organizations to promote, protect, and preserve the health of those in the community. It involves community development, community organization, community participation, and community diagnosis. Community health is affected by physical factors (geography, the environment, community size, industrial development, socio-cultural factors (beliefs, traditions, prejudices, economic status, politics, religion, and social norms, individual behavior, and community organization. Whereas public health is government-driven, community health is community-driven. Communities both in pre-history and the historical era undertook measures to protect health. Before the 1980s emphasis was on public health. After that the importance of community health and community participation were recognized.

UNIT OUTLINE

1.3.1 DEFINITION OF PUBLIC HEALTH

A. Public Health As Health Promotion, Health Protection, and Disease Prevention

B. Public Health as Social Reform

C. Scope and Challenges of Public Health

D. Essential Public Health Functions

E. Methodology of Public Health

1.3.2 DISCIPLINES THAT ASSIST PUBLIC HEALTH

A. Quantitative Disciplines

B. Economic Disciplines:

C. Social Science Disciplines

D. Communication:

E. Management Sciences:

1.3.3 PUBLIC HEALTH PROGAMS and STRATEGIES

A. Public Health Policy

B. Disease Prevention and Health Promotion

C. Medical and Social Services

D. Environmental Protection

E. Public Health Strategies

1.3.4 HISTORY OF PUBLIC HEALTH

A. Public Health in Ancient Civilization

B. Development of Public Health in the UK

C. Development of Public Health in the US

1.3.5 COMMUNITY HEALTH

A. Definitions

B. Community Health in Ancient Civilizations (Up To 500 CE)

C. Community Health (500 – 1800 CE)

D. The Renaissance and Age of Exploration (1500-1700 CE)

E. Community Health in the Modern Era 18^th-20^th Centuries CE

1.3.1 DEFINITION OF PUBLIC HEALTH

A. PUBLIC HEALTH AS HEALTH PROMOTION, HEALTH PROTECTION, AND DISEASE PREVENTION

B. PUBLIC HEALTH AS SOCIAL REFORM

Public health had developed as a reaction to bad health and social conditions. It has been a reform movement that at times has been more social reform than medical science. The discipline alternates between the scientific and social reform modes depending on the challenges. In the 19^th century medicine was just one of many components of public health. Social workers, engineers, lawyers, and other social activists were active in the public health movement. By the early 20^th century the medical model had become predominant and thenceforward public health practitioners became physicians only.

C. SCOPE and CHALLENGES OF PUBLIC HEALTH

The scope of public health covers health problems and disease determinants. Health problems include infectious diseases, chronic diseases, trauma, and mental disorders. Disease determinants include nutrition, environment, occupation, life-style and population dynamics, and socio-demographic factors.

Public health faces many challenges in view of its wide scope. The demographic challenge is in the form of rapidly changing demographic parameters: the demographic transition with the associated epidemiologic transition, rapid communication and movement of people information and ideas in a global village. Human will and behavior remains an intractable barrier. There are gaps between biomedical knowledge and human will (behavior and social action), and between clinical medicine and public health. Resources for public health programs are limited and have to compete with curative services. Distributive justice in health care allocation is a still a problem and it becomes more severe as medical technology becomes increasingly more sophisticated. Ethical issues are also on the rise: informed consent, privacy of medical information, ethico-legal considerations in in-vitro fertilization, organ transplantation, life support and terminal illness, abortion and contraception; individual autonomy vs. public good.

D. ESSENTIAL PUBLIC HEALTH FUNCTIONS

The essential public health functions are: prevention of disease (epidemics & endemic) as well as injuries; protection against environmental hazards and respond to disasters; promotion of healthy behavior; assurance of quality and accessibility of health services; support of health services planning, development, management, and evaluation; development of health resources (financial, human, and technological); provision of personal health activities; and provision of community health services. Personal health services include preventive and curative activities that affect individuals and the immediate family. Community health services translate into protection and improvement of general population health and include measurement of disease and injury, control of disease both communicable and non-communicable, school health services, maternal and child health services, services that deal with needs of special populations such as minorities, community mental health services, alcohol and drug abuse services, health care delivery systems, environmental health, injury control, occupational health and safety.

E. METHODOLOGY OF PUBLIC HEALTH

Public health uses the scientific approach to solve problems. Both medical and social science techniques are employed. However public health actions do not have to wait for development of perfect knowledge. Often action is taken with imperfect or incomplete knowledge. The following sciences are employed in public health: epidemiology, biostatistics, biological sciences, physical sciences, demography, and vital statistics. Among the social sciences that contribute most to public health are: economics, sociology, communication, operational systems analysis, planning & management, social policy and social administration.

1.3.2 DISCIPLINES THAT ASSIST PUBLIC HEALTH

A. QUANTITATIVE DISCIPLINES

EPIDEMIOLOGY

Epidemiology is the basic science of public health. Epidemiology and public health share two common features. They both deal with the triangle of disease-host-environment. They both use the time-person-place triad to describe phenomena. The specific contributions of epidemiology to public health are: description of the spectrum of disease, description of the natural history of disease, Identification of risk factors of disease, prediction of disease trends, elucidation of the mechanisms of disease transmission, testing the efficacy of intervention strategies, Evaluation of intervention programs, identification of health needs of the community, and evaluation of public health programs.

BIOSTATISTICS

Biostatistics is used to collect, manage, and analyze data to draw conclusions of public health importance.

OPERATIONAL RESEARCH

Operational research is a rapidly growing field with a potentially big contribution to public health. It uses mathematical models to understand operations and make decisions. It uses probability models, optimization models, and decision analysis techniques. Operational research has public health applications in health care facilities management, regional health planning, and clinical decision making. The following aspects of health care facility management are involved: appointment systems, admission/discharge scheduling, facility sizing, facility staffing, and patient flow models. Regional planning involves needs assessment and facility location.

B. ECONOMIC DISCIPLINES:

The inter-dependence between public health and economics is very close. Economic conditions directly affect the health of the population. The economic resources available at the individual and national levels determine the type of medical care and public health interventions. On the other hand public health interventions affect the proportion of the population that is engaged in economically productive activities by affecting birth and death rates. Economic activities such as industries directly affect health by their effect on the environment. Economic analysis is necessary because health care resources are scarce. The following indices are usually made by health economists: elective cost, cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis.

C. SOCIAL SCIENCE DISCIPLINES

SOCIOLOGY:

Sociology being a study of human societies is needed in public health. There are social causes of disease. Disease and its treatment have social impact. Medical sociology is a sub-discipline of sociology concerned with health policy and social factors in medicine. Both quantitative and qualitative research is used often combined.

SOCIAL POLICY:

Social policy is a discipline that makes major contributions to public health. Social policy reflects political policy. It is closely intertwined with economic changes. The growth of the welfare society and the calls for welfare reform gave impetus to major developments in social policy. Social policies have public health implications. Poor housing and low income are associated with poor health outcome. Social class and the level of public expenditure on health also impact on health status. Among other issues addressed by social policy are issues of equity and women health.

D. COMMUNICATION:

Public health is concerned with changing human behavior for better health and well-being. The information revolution has put at the disposal of the public health practitioner many new methods of communication technology to supplement the traditional ones.

Television: Advertisement and TV have a big impact on human consumption patterns. They have a direct impact on nutrition, leisure activities, life-style, and violent behavior.

Health education involves giving people evidence so that they can make appropriate decisions about their health when confronted by media bombardment or peer pressure.

The communication process involves the sender, the channels and the recipients. The channels may be 2-way face to face, one-way, or environmental (for example the food outlets affect dietary behavior). The recipients of health communication may be individuals, social networks, organizations, and communities.

Communication sites: Schools are a good opportunity for life-style change especially in adolescents. The workplace is also an opportunity for health communication. Health communication can also be effective at the points of purchase. Mass media campaigns can reach many people at the same time.

The planning of health communication programs involves: problem identification, commitment, planning (needs assessment, pretest of the educational material, and evaluation of the educational method), implementation, and evaluation.

E. MANAGEMENT SCIENCES:

The role of management and planning in public health has been recognized only recently. Public health involves management roles, management functions, and management skills. Management roles can be interpersonal, informational, and decision-making. Management functions are: planning, organization, leadership, motivation, change, decision-making, directing, controlling, and conflict resolution. Managerial skills are technical, human, and conceptual.

The classical organizational theory by Max Webber envisaged a bureaucracy. It has been challenged because it ignored informational organizations. The systems theory of organization is perhaps more applicable to the health field.

The health care organization has the following characteristics that distinguish it from other types of organization: altruism, non-profit motivation, measurement of results in the long-term, and an archaic organizational structure. When evaluating an organization the following are taken into consideration: history, environment, structure, organizational systems (eg planning, documentation, communication, inter-personal relations etc).

Future: Management issues that are likely to face public health in the future are: measurement of organizational performance, assessment of outcome and effectiveness of medical and public health interventions, cost-benefit and cost-effectiveness analysis, policy and decision-making, management information systems, and social marketing.

1.3.3 PUBLIC HEALTH PROGAMS and STRATEGIES

A. PUBLIC HEALTH POLICY

Public health policy determines the organizational structure as well as resource allocation. The structure of public health programs may be centralized or decentralized. There are advantages and disadvantages of each of these two modes of program delivery. Resource allocation is about determining who gets what services. A fine balance needs to be established between curative and preventive services. Issues of justice and equity arise in the process of allocating scarce resources. Need-based allocation raises the issue of how to measure health needs objectively and fairly. Health insurance coverage also raises issues of coverage for the uninsured and what services insurance can cover. The purposes of public health are achieved through various programs. These are disease prevention, health promotion, medical care, influencing behavior, and environmental control. Vital statistics play a major role in public health planning and evaluation.

B. DISEASE PREVENTION and HEALTH PROMOTION

Control of infectious disease: immunization, screening programs, contact tracing, disease surveillance, epidemic investigation and control.

Health education: health information dissemination through the media, schools, and community groups.

Maternal and child health: genetic counseling, genetic screening, family planning, prenatal care, well child care, school health services, disabled children services, and Medical social work

Chronic diseases control: screening programs, education

Occupational Health Programs: Health education, immunizations, screening

Dental public health: Screening and referral, water fluoridation, education on nutrition and dental hygiene

Public health nursing

Nutrition: Nutritional education, nutritional supplementation for women and children

Consumer protection

Public health laboratory: Support for environmental, occupational, and infectious disease control programs

Mental health: education, community support for discharged patients, alcohol and addiction services

School health

Screening

C. MEDICAL and SOCIAL SERVICES

Medical and nursing services for early diagnosis and treatment of disease

Care for the elderly

Social welfare services needed for health

D. ENVIRONMENTAL PROTETION

Environmental sanitation

Air pollution control

Water and sewage control

Occupational health

Food hygiene and inspection: inspection of restaurants,

Animal health

Housing inspection

Insect and rodent control

E. PUBLIC HEALTH STRATEGIES

SURVEILLANCE

Public health surveillance is a continuous process of monitoring and analysis to be able to identify problems early

INTERVENTION

Public health intervention is against disease and its determinants

EVALUATION

The results of evaluation of public health programs are used to guide further action

ECONOMIC STRATEGIES WITH IMPACT ON HEALTH

Role of socio-economic development

Infra-structure

1.3.4 HISTORY OF PUBLIC HEALTH

A. PUBLIC HEALTH IN ANCIENT CIVILIZATION

Public health as organized efforts in disease prevention and health promotion is a relatively recent phenomenon in human history. During pre-history and for most of the historical period humans were more concerned with curing diseases in individuals. There were however isolated public health efforts but these could not be developed to much sophistication because the governmental and social organizational structures were not always strong enough. The Hammurabi code in ancient Mesopotamia was an effort at instituting some public health measures. The Romans undertook a lot of public health measures. The Muslim civilization made many contributions to public health. There was little development of public health services in Europe in the dark ages (500 – 1500 CE) and the post reformation pre-industrial era (1500 – 1850 CE).

B. DEVELOPMENT OF PUBLIC HEALTH IN THE UK

Period of complacency: Organized public health services have a very recent history in the UK. In the Victorian era (1837-1902) Britain became an industrial power with unprecedented wealth. There was marked decline in mortality from infectious disease that is attributed to improved nutrition and standards of living. The Victorian era had many public health problems arising out of rapid industrialization and the rural-urban exodus. The government response to these problems was adhoc and permissive until the mid-19^th century.

Awakening: The cholera epidemics of 1831-2 and 1865-66 led to a more serious interest in public health. Sir Edwin Chadwick (1800-1890 CE) was Secretary of the Poor Commission. In 1842 he published his ‘Report on the Sanitary Conditions of the Laboring Population based on extensive field surveys. The Chadwick report emphasized the link between dirt, crowding, and disease. Public health measures started being taken. following the passage of the Public Health Act of 1848. Edwin Chadwick became a member of the General Health Board that was concerned with sanitation and sewage disposal. Due to his strong advocacy for public health that conflicted with vested interests, Chadwick was forced to retire at the early age of 54. The landmark legislation by the Public Health Acts of 1872 and 1875 established a sanitary authority in every district. Housing laws of the 1870s included health codes. In 1872 local authorities were required to appoint a medical officer of health (MOH) whose work was mostly in sanitation and disease control. The 1888 local government act required appointment of medically-qualified medical officers of health. School health programs started from 1890. Schools for children with disabilities were started from 1908 CE. Measures were taken to decrease the high infant mortality rate by visits to homes. Sanitaria were established for tuberculosis patients with emphasis on rest and open air as methods of treatment. Pasteurization helped decrease TB transmission. By the end of the 19^th century clean water supplies were available for all.

Changing scope: The scope of public health has been changing. The germ theory of disease that became popular in the closing years of the 19^th century narrowed the focus of public health to the infectious disease model leaving out aspects that we know today to be important for public health. In 1939 the focus of public health was widened when local authorities were permitted to provide Maternal and Child Health Services (MCH), child welfare services, school-based medical services, school meals including milk, and anti-tuberculosis schemes. The era of the 1940s saw the popularization of the concept of social medicine. The concept however failed to make a major impact.

National Health Service: With the establishment of the National Health Service after the Second World War, the focus of public health was widened even further. The MOH took on responsibilities for administrative responsibilities that included ambulance services, home help, and old people's homes. In 1968 changes in the NHS saw the emergence of community physicians who provided primary health care under the purview of the MOH. Debates are on-going about the reform or even replacement of the NHS with no clear consensus emerging as yet. The tendency to privatization of health care is strong and is favored by the economic climate of the 1990s.

C. DEVELOPMENT OF PUBLIC HEALTH IN THE US

Port Health and quarantines: The first public health concerns were port health and control of epidemic diseases (yellow fever, plague, and cholera). Port cities like New York and Philadelphia had a 40-day quarantine period for ships arriving from overseas. Coherent policy about control of epidemic diseases could not be formulated because there were disputes about the cause of these diseases in the 19^th century. The microbial basis of disease did not become popular until the end of the 19^th century.

The impact of the civil war: The American civil war stimulated renewed interest in public health when it was observed that more soldiers from both sides died of disease than of bullets. After the war, state health boards were established in Massachusetts in 1869, California in 1870, District of Columbia in 1871, Virginia in 1872, Minnesota in 1872, and Maryland in 1974. Congress created a National Board of Health in 1879 following a yellow fever epidemic in the south of the US. The board, supposed to deal with quarantines, was disbanded in 1883 and its duties were transferred to the Marine Hospital Service, the forerunner of today's National Institutes of Health.

In Massachusetts, Lemuel Shattuck in 1850 drew up a report for the state of Massachusetts recommending establishment of a board pf health, collection of vital statistics, sanitary measures, research on diseases, health education, control of exposure to alcohol and smoke, control of adultered food, and control of quack medicines. The year 1850 marked the start of the era of modern public health. New York passed a law on adulteration of milk in 1856. The first sanitary survey was carried out in New York City in 1864. The Port Quarantine Act was passed in 1878. Pasteurization of milk started in 1890. Milk inspection started in 1891. The first nurse was appointed in 1895. Septic tanks started in 1895.

Public Health Reform Movement (1900-1920)

In this period there was a lot of public agitation for better public health. Government also undertook measures to protect public health. The Pure Food and Drugs Act was passed in 1906 to control drugs. New York State passed the workmen compensation act in 1910 and the first occupational health clinic was set up in 1910. On the educational and training front, the first nursing program started in New York in 1902. In 1918 the Johns Hopkins University set up the first school of public health. The Harvard School of Public Health was set up in 1923.

Tropical diseases & military adventures: The American-Spanish of 1898 fought in both Cuba and the Philippines was another stimulus to public health since it was realized that the toll of death due to infectious disease was very high. As a result a program against yellow fever was started in Cuba and a Tropical Diseases Bureau was set up in the Philippines. An intensive campaign again mosquitoes led to control of yellow fever and enabled the completion of the Panama Canal whose construction had been abandoned because of disease. Efforts on tropical diseases within the US also started. The Rockefeller Foundation, starting in 1909, worked on control of hookworm infestation in the south of the US.

Expanding role of public health: In 1912 the role of the United States Public Health Service was expanded to include investigation of disease and sanitation. Towards the end of the 19^th century, bacteriology gave a new impetus to public health by establishing the bacteriological approach which emphasized the disease orientation. By the 1920s public health was dominated by medical persons. Sanitary and other professions like municipal engineers, lawyers, and social reformers who had been part of the public health reform movement took a lower profile. Schools of public health were also established in the 1910s at Harvard, Johns Hopkins, Yale, and Columbia. The impetus for the establishment of these schools was to provide trained manpower for the expanding public health services. The popularity and funding of public health schools has waxed and waned with public interest in public health. The schools expanded rapidly during the Great Society programs of the 1960s when funding for public health increased phenomenally.

The First World War: The First World War was another new stimulus for public health concerns by revealing the poor general health situation of the population; many young men called up for service had to be rejected because of poor health. Renewed concern with public health started. In 1912 the United States Public Health Service (USPHS) started helping states develop public health departments. The 1935 Social Security Act provided funds to states through USPHS for public health. Grants were made for public health training as well as specific programs like maternal and child health, mental health, crippled children, and tuberculosis.

1920s: The Rockefeller Foundation was established in 1919 and it started funding health programs. In general the 1920s were a period of slow growth except for initiatives funded by the Rockefeller and Milbank Foundations. The major achievement of this era was perhaps the prohibition of alcohol which was accompanied by decline of alcoholism and alcohol—related disease. By 1937 the average life expectancy was 59.7 years.

The great depression (1929-1935): The government intervened more actively by initiating several public health programs because the private sector lacked the resources to cover the needs. The Social Security Act of 1935 had several enactments relating to public health. In 1937 the National Cancer Institute was established by act of Congress.

The Second World War also did reveal the poor state of the general health of the population; 40% of the young men called up were declared unfit to serve in the armed forces for poor health. As a result funding of public health programs was seen as part of the defense policy. USPH expanded its programs for states. The Centers for Disease Control (CDC) was created after the war. In the post-world war II era, states turned their attention to chronic diseases. Federal grants were made in 1946 for cancer control and in 1948 for heart disease prevention. The war also stimulated medical research. Penicillin and DDT were discovered and were used in the war years.

Post-War period: There was a decline in public health in the post-war era due to various reasons. The focus on bacteriology emphasized curative medicine using drugs to eliminate disease without the necessity for public health measures. The political atmosphere of the 1950s did not support public health. The number of students entering public health training declined since federal support was ear-marked for research and not faculty salaries. In the late 1940s and early 1950s the concept of social medicine was proposed but it did not gain acceptance. In the period 1946-1960s hospital construction increased under the 1946 Hill-Burton Act (National Hospital Survey and Construction Act). The discovery of the polio vaccine gave a boost to infectious disease control by immunization. President Eisenhower’s heart attack stimulated the exercise movement.

Period of Social Engineering (1960-1980): In the 1960s the Great Society and War against Poverty programs resulted into increased government funding for public health. The federal government became involved payment for medical care and environmental regulation. The Medicaid and medicare bills were passed in 1965. They increased access to health services but had the unwanted effect of increasing the cost of health services. Schools of public health responded by offering new training programs in health policy and management, mental health, population control, environmental health, and international health. Enrolment in public health schools increased tremendously. By the 1970s public health programs of various kinds were offered by states.

Health Promotion period (1980-1990): By the mid 1970s health promotion and disease prevention were recognized as priorities. The Centers for Disease Control concluded in 1975 that about 48% of premature deaths were due to lifestyle (lack of exercise, high fat diet, smoking, and stress). In the 1980 the US published 226 objectives for the nation in the field of disease prevention and health promotion divided into three categories: preventive services, health protection, and health promotion. The objectives were based on the 1979 Surgeon-General’s Report titled ‘Healthy People: National Health Promotion and Disease Prevention Objectives’.

The Reagan revolution of the 1980s cut funding for many of the great society programs. When the AIDS epidemic surfaced it was decided to fund it nationally rather than through states.

Community Health in the 1990s: The major problems are: rising health care costs and barriers to access, environmental concerns, life style diseases (cancer, stroke, and injuries), communicable diseases (HIV, Lyme’s disease), abuse of alcohol and drugs

1.3.5 COMMUNITY HEALTH

A. DEFINITIONS

Community: is defined as a group of people with a shared location, shared environment, and shared fate. A community can be further characterized geographically, socially, and by behavior.

Health was defined by the World Health Organization (WHO) in 1947 as ‘health is a state of complete physical, mental, and social well being and not merely the absence of disease or infirmity.

Community development refers to efforts made to create conditions of economic and social progress for a whole community with its full participation or under community initiative.

Community organization is planned efforts in which individuals and organizations influence social problems based on consensus. Community organization starts with recognition of the problem. Community stakeholders are then involved and the people are organized to undertake needs assessment and community diagnosis. Priorities are determined and goals are set. Intervention activities are planned and are implemented. Evaluation and feedback are necessary. Plans must be made to maintain continuity.

Community participation consists of mass mobilization, social action, community service, and community advocacy.

Community diagnosis is diagnosis of the health problem at the level of the community and not the individual. It includes a complete understanding of the health problem including causes. Its results are the basis for community-based intervention. Cross-sectional studies are needed for community diagnosis. The community must participate in both the diagnosis and also the formulation of public health solutions.

Community Health involves both private and public efforts of individuals, groups, and organizations to promote, protect, and preserve the health of those in the community. Community medicine, a subdivision of community health, is defined as prevention of illness and promotion of health in the context of the community. Synonyms of community health are community medicine, or social medicine. Community medicine is the same as preventive medicine and is concerned with disease prevention and health promotion.

Factors the health of a community: The growth of the community health movement has highlighted many factors hitherto unknown to have an impact on community health. The physical factors that affect community health are geography, the environment, community size, industrial development. The socio-cultural factors that affect community health are beliefs, traditions, prejudices, economic status, politics, religion, and social norms. Community health is also affected by individual behavior and the methods of community organization.

B. PUBLIC HEALTH VS COMMUNITY HEALTH

The distinction between public and community health is not easy to define because the two terms are used interchangeably. The term public health was used earlier than the term community health and we can perhaps define the difference between the two based on history. The public health movement that became strong in the mid 19^th century was aimed at getting governments or public authorities to take action to improve health. This meant that public health was a governmental function carried out by public authorities. By the 1960s new ideas of personal freedom, autonomy, and empowerment became prominent. Individuals and groups of individuals developed more awareness of their health and environmental problems and desired to be involved both in the identification and solution of the problems. The genesis of community medicine therefore was this non-governmental organization movement. The trend to more popular involvement in community health was aided by the fall and therefore discredit of authoritarian centrally-planned regimes in the former Soviet Union and its satellite states in Europe, Asia, and Africa. Growing privatization of the economic systems and withdrawal of the state from providing health and other social services have led to growth of community power and community health. People now organize themselves to solve their health problems

C. COMMUNITY HEALTH IN ANCIENT CIVILIZATIONS (UP TO 500 CE)

Archeological findings in India show that in about 2000 BC bathrooms and drains in homes and sewers at street level. Drainage systems were known in the middle Egyptian Kingdom (2000-2700 BC). In 1600 BC Myceans in Crete had toilets, flushing systems, and sewers. Sumerian clay tablets wrote about medical prescriptions in about 2100 BC. By 1500 BC Egyptians knew more than 700 drugs. The Book of Levictus written in about 1500 BC had guidelines on personal cleanliness, sanitation of camp sites, disinfection of wells, isolation of lepers, disposal of refuse, and hygiene in maternities.

GRECO-ROMAN PERIOD (500 BC to 500 CE)

The Greeks engaged in sports and exercise that are very modern forms of health promotion. They had water supplies to cities that were improved by the Romans. The Romans built sewage systems, regulated building construction, refuse collection, street cleaning, and street repair. Romans also started hospitals. The Romans however did not extend medical thinking. By the fall of the Roman Empire public health activities had ceased.

C. COMMUNITY HEALTH (500 – 1800 CE)

MIDDLE AGES (500-1500 CE)

In the medieval period, Greco-Roman knowledge declined and was forgotten in Western Europe but was preserved in Byzantine. In the medieval times disease was seen as punishment for sin. Cure of diseases was seen as being both physical and spiritual. Failure to understand the environmental basis of disease led to repeated epidemics of plague in 543, 1348, and 1664 CE. The 1348 plague, called the Black Death, killed 25 million people. Other epidemics were: smallpox, diphtheria, measles, influenza, tuberculosis, anthrax, and trachoma. Syphilis started in 1492 CE.

D. THE RENAISSANCE AND AGE OF EXPLORATION (1500-1700 CE)

The period of travel and exploration led to rapid exchange of ideas. European explorers spread European diseases to unprotected natives. It was realized that for some diseases like malaria (bad air) the environment was an important factor. Careful description of symptoms led to distinction of typhus and malaria as separate diseases. The epidemics of smallpox, malaria, plague still occurred.

E. COMMUNITY HEALTH IN THE MODERN ERA 18^th-20^th CENTURIES CE

OVER-VIEW

The 18^th century was a period of industrial growth. Living conditions were poor in the overcrowded industrial towns. Workplaces were unsafe. In the 19^th century living conditions remained unsanitary as urbanization expanded. Better agriculture led to better food production and better nutrition. Epidemics of cholera occurred in London and other European cities. The predominant theory for disease causation was the miasma theory which assumed that vapors or miasma were the cause of disease.

UNITED STATES OF AMERICA

Social reform movement: The period 1900-1920 was known as the period of the reform movement in public health. With industrial growth in the late 19^th century, urban health problems increased and cities were hardly coping. As a response to the urban problems, public health was transformed into a social reform movement. The American Public Health Association (APHA) was formed in 1972 as an outgrowth of this reform movement. Membership of APHA, besides medical professionals, attracted scientists, municipal officials, engineers and others. Other voluntary organizations were formed to fight for improved housing, abolition of child labor, provision of maternal and child health services, and promotion of temperance. The following are the major organizations formed in that period: the American Red Cross formed in 1882, the National Association for the Study and Prevention of Tuberculosis in 1902, the National Tuberculosis Association in 1904, the American Social Hygiene Association in 1905, the National Committee for Mental Hygiene in 1902, the American Cancer Society in 1913, and the American Society for the Control of Cancer in 1919.

Growth of knowledge

In 1900 Major Walter Reed announced his discovery that mosquitoes transmitted yellow fever. In 1862 Louis Pasteur proposed the germ theory of disease. Robert Koch proposed criteria for diagnosis of bacterial disease. The period 1875-1900 was the bacteriological period of public health. The leading causes of death at the close of the 19^th century were communicable diseases: influenza, pneumonia, TB, GIT infections, typhoid, malaria, diphtheria, pellagra, and rickets.

ILLUSTRATIONS

EXERCISES: TRUE/FALSE QUESTIONS

1. The following are true about the discipline of public health

Public health is undertaken only by the government
Individuals and communities are usually opposed to public health programs
Health promotion is an objective of public health
Health protection is not an objective of public health
Health maintenance is a concern of clinical medicine and not public health

FFTFF

2. The following are true about the discipline of public health

Disease prevention is the only function of public health
The 2 paradigms of public health are disease prevention and health promotion
Environmental protection is not a concern of public health
Public health is not interested in disease determinants
Public health is a discipline useful only in poor under-developed countries

FTFFF

3. The following statements are true about the discipline of public health

Epidemiology is a basic science of public health
Public health is completely divorced from clinical medicine
Sanitation is not a concern of public health
Nutrition is an important function of public health
Housing is a concern of engineers and not of public health officials
Improvements in health over the past 50 years are due only to clinical medicine
Immunization is not considered a preventive public health intervention

TFFTFFF

4. The following are essential functions of public health

Prevention of disease and injuries
Protection against environmental hazards
Promotion of healthy behavior
Assurance of quality and accessibility of health services
Provision of personal and community health services

TTTTT

5. The following statements are true about public health interventions

Public health uses the scientific approach to solve problems
Public health interventions have to wait for proof of causality
Public health action may be based on imperfect information
Public health relies on biostatistics and epidemiology
Operations research is not a concern of public health
Economics is not relevant to public health intervention
Social policy has a major role in public health
Sociological research helps in solving some public health problems
Public health practitioners need not be good in communication

TFTTFFTTF

6. The following are public health strategies

Intervention
Surveillance
Military action
Evaluation
Police actions

TTFTF

7. The following statements are public health programs and strategies

Public health starts with health policy formulation
Disease prevention and health promotion
Medical and social services
Environmental protection
Police protection

TTTTF

8. The following statements are true about the history of public health

The Chadwick report had a lot of impact on public health in the UK
The National Health Service was established in 1948
The 1935 Social Security Act in the US provided funding for public health
The Medicare and Medicaid bills in the US were passed in 1965
Rising health costs is not a major public health problem today

TTTTF

9. The following statements are true about community health

A. Community health is based on community action and is not government-driven

B. Community health is not concerned with health promotion or protection

C. Community health is not affected by geographical and environmental factors

D. Socio-cultural factors have an impact on community health

E. Community participation is not necessary in community health programs

TFFTF

EXERCISES: COMPUTATIONS

EXERCISES: JOURNAL STUDY

Using the internet or online data-bases identify and summarize the following

1. One articles on the history of public health

2. The Alma Ata Conference on Primary Health Care in 1978

EXERCISES: PRACTICAL ASSIGNMENTS

Using the website of the Ministry of Health, identify agencies that are involved in public health activities
List all public health positions/titles in the Ministry of Health explaining the duties of each
Using the WHO website describe the composition and activities of the World Health Organization
Using the internet summarize the activities of the American Public Health Association (APHA)
Using the internet summarize the activities of the Institute of Public Health, Kuala Lumpur

UNIT 1.4

INTRODUCTION TO BIO-STATISTICS

Learning Objectives

· Definition, scope, and role of bio-statistics in medicine

· Definition of descriptive and inferential biostatistics

· Difference between substantive and statistical conclusions

· Uses and limitations of bio-statistics

Key Words and Terms

· Biomathematics

· Biometry

· Biostatistics

· Mathematical Computing

· Numerical Analysis

· Numerical Data

· Statistical Conclusion

· Statistical Methods

· Statistical questions

· Statistics And Decisions

· Statistics, analytic statistics

· Statistics, applied statistics

· Statistics, descriptive statistics

· Statistics, health Statistics

· Statistics, inferential statistics

· Statistics, mathematical statistics

· Statistics, medical Statistics

· Statistics, theoretical statistics

· Substantive Conclusion

· Substantive Question

UNIT SYNOPSIS

1.4.1 BIOSTATISTICS AS A DISCIPLINE

The term statistics can be used to convey three meanings. Applied statistics is defined as techniques of articulating, summarizing, analyzing, and interpreting numerical information. Theoretical statistics deals with probability. Statistics are indices or summary statistics derived from data. Bio-statistics is a branch of applied statistics that is management and analysis of numerical data on people, health, disease, medical treatments and procedures. It includes vital statistics, public health statistics, and demography. Biostatistics is divided into 2 branches: descriptive and analytic. Descriptive statistics deals with collection, organization, presentation, and summarization of data. Analytic statistics deals with drawing logical and objective conclusions about a sample or a population. Biostatistics provides the tools for the summary and digestion of a lot of numerical laboratory and clinical data including critical reading and understanding of scientific literature.

1.4.2 HISTORY OF BIOSTATISTICS

Statistics has grown through successive eras: era of censuses, era of vital statistics, era of descriptive statistics, era of analytic statistics, and era of probability statistics. Ancient civilizations counted their populations for taxation and military purposes. Complete census were first carried out in Sweden in 1749, the US in 1790, Spain in 1798, England & Wales in 1801, and Canada in 1871. John Graunt is considered the founder of vital statistics. He analyzed London mortality data and also laid the foundations of the science of demography. William Farr started the modern procedures of vital statistics registration. Pierre Charles Alexandre Louis (1787-1872) introduced the numerical method in describing medical facts quantitatively.

The 19^th century and early 20^th centuries witnessed many theoretical developments. Karl Pearson (1857-1936) introduced the mode, mean deviation, coefficient of variation, moments, measures of symmetry and kurtosis, the chi-square, symbol of the null hypothesis (H₀), type 1 and type 11 errors, homoscedacity and heteroscedacity, and the concept of partial correlation. Sir Arnold Fisher (1890-1962) introduced variance, methods for small samples, factorial designs, the null hypothesis, random allocation, ANOVA, ANCOVA, relation between regression and ANOVA, and testing significance of the regression coefficient. Karl Pearson and RA Fisher developed contingency table analysis using the chi-square test. Adolph Quetelet developed vital statistics in its modern form and introduced the concept of the mean. KF Gauss (1777-1855) introduced the median, re-discovered the normal distribution that has independently been discovered before Pierre Simon Marquis de Laplace (1749-1827) and in 1733 by Abraham de Moivre (1667-1754). Sir Francis Galton used the term ‘normal’ to refer to the curve, applied statistical techniques to natural phenomena, described correlation and regression. W.F. Sheppard introduced the standard normal curve in 1899. C Kremp published the first table of the area under the curve in 1799. J Neyman developed the concept of confidence intervals in 1934. Charles Spearman (1863-1945) and Maurice George Kendall (1907-1983) introduced non-parametric tests. The bulk of statistical theory is probability theory since modern inferential statistics depends on probability theory. Christian Huygens (1629-1695) was the first one to publish on probability and games. Modern probability theory owes a lot to the pioneers: Blaise Pascal (1623-1662), Pierre de Fermat (1601-1665), Jacques Bernoulli (1654-1705), Nicolas Bernoulli (1687-1759), Abraham de Moivre (1667-1754), Pierre Raymond de Montmart (1678-1719), and Pierre Simon Marquis de Laplace (1749-1827).

1.4.3 LIMITATIONS OF BIOSTATISTICS

An investigator starts with a substantive question that is formulated as a statistical question. Data is then collected and is analyzed to reach a statistical conclusion. The statistical conclusion is used with other knowledge to reach a substantive conclusion.

Statistics has several limitations. It gives statistical and not substantive answers. The statistical conclusion refers to groups and not individuals. It only summarizes but does not interpret data.

Statistics can be misused by selective presentation of desired results. Computation is not an end in itself. It is a tool that can be used well or can be mis-used. A human must have a clear idea of what is required of the computer and must instruct it accordingly. The human must also be able to intelligently interpret the output from the computer. All who tinker with computers must remember the adage ‘rubbish in/rubbish out’.

1.4.5 CAREER OPPORTUNITIES IN BIOSTATISTICS

Biostatistics finds practical applications in quantitative research, administration, and decision-making. Statisticians work in universities, the public sector, and the private sector.

UNIT OUTLINE

1.4.1 BIOSTATISTICS AS A DISCIPLINE

A. Statistics

B. Biostatistics

C. Importance of Biostatistics

D. Scope of Biostatistics

E. Rationale of Learning Biostatistics

1.4.2 HISTORY OF BIOSTATISTICS

A. Ancient Times:

B. Era of Vital Records:

C. Population Studies

D. Era of Descriptive Statistics

E. Era of Analytic Statistics

1.4.3 LIMITATIONS OF BIOSTATISTICS

A. Statistical Vs Substantive

B. Analysis Vs Interpretation:

C. Misuse of Statistics:

D. Mis-Use of the Computer:

1.4.4 CAREER OPPORTUNITIES IN BIOSTATISTICS

A. Practical Applications

B. Types of Statistical Practice:

C. Statistics Careers In The University

D. Statistical Careers in the Public Sector

E. Statistical Careers in the Private Sector

1.4.1 BIOSTATISTICS AS A DISCIPLINE

A. STATISTICS

Statistics is a branch of applied mathematics. The term statistics has got 4 different meanings that are used interchangeably and in a confusing way. (a) Applied statistics is collecting, organizing, describing, analyzing, interpreting, and presenting a set of quantitative data. It can also be defined as techniques of articulating, summarizing, analyzing, and interpreting numerical information. (b) Theoretical statistics deals with probability, its various theories, and applications. (c) Statistics can also be used to refer to indices derived from data such as rates, proportions, and percentages. An alternative way of stating this is to say that statistics are facts stated numerically. (d) Statistics could also mean summary of sample characteristics such as averages or percentages. Statistics is to the sample what parameter is to the population.

B. BIOSTATISTICS

DEFINITION

Bio-statistics is a branch of statistics that is management and analysis of numerical data on people, health, disease, medical treatments and procedures. Vital statistics, public health statistics, and demography are generally considered under biostatistics. Vital statistics are bio-statistics dealing with births, deaths, illness, marriage, and divorce. Public health statistics include: nutrition, sanitation, epidemiology, maternal and child health. Demography is study of population dynamics by statistical methods. Biostatistics is divided into 2 branches.

DESCRIPTIVE BIO-STATISTICS

Descriptive statistics is the traditional domain of bio-statistics. It describes characteristics of a population or a chosen group. Descriptive statistics deals with collection, organization, presentation, and summarization of data. Descriptive bio-statistics started as vital statistics of birth, death, fertility, and disease occurrence and with the availability of the computer it has developed to become very sophisticated. One of the most important aspects of descriptive statistics is the national decennial census. It describes the population structure, economic and social activities of the country.

INFERENTIAL BIO-STATISTICS

Inferential statistics or inductive statistics is involved in the 3 main components of the scientific method (formulation of the hypothesis, experimentation or observation, and statistical reasoning or conclusion). The scientific method is used in predicting and establishing causal associations. Inferential Statistics is the bulk of contemporary statistical work. Concepts and methods of inferential statistics are involved in the design, execution, analysis & interpretation of studies. Statistical inference is inductive, information from a small sample is used to infer on a larger population; this contrasts with mathematics that is deductive i.e. working from the general to the specific. It deals with drawing logical & objective conclusions about the sample or the population. The term sampling statistics is used to refer to inferential statistics in which sample information is used to draw conclusions about a population. Inferential statistics is used in prediction. It starts by establishing the mathematical relation between 2 factors. The relation is then used to make predictions of events for which there is no empirical data. There are techniques for testing how good the prediction is.

C. IMPORTANCE OF BIOSTATISTICS

QUANTIFICATION AND NUMERICAL DATA (numeracy)

Biostatistics is important as a quantitative science. Measurement and counting are very important because quantitative information is basis for growth of civilization. Thinking is more effective and more logical when objects can be quantified exactly. Mathematics is a universal and exact language of scientific communication. Statisticians invoke the curse of Kelvin that states that if you cannot express it in numbers you do not understand it (Feinstein AR (1971): On exorcising the ghost of Gauss and the curse of Kelvin. (Clin Pharm Ther 12:1003). We are now living in the age of information and numerical data. There is a lot of quantitative medical and health information. Bio-statistics is needed to digest, summarize, understand and use that information.

D. SCOPE OF BIOSTATISTICS

Knowledge of basic concepts in statistics is necessary for understanding scientific reports that are couched these days in a lot of scientific or statistical jargon. Design, execution, and analysis of observational and experimental studies require knowledge of statistical principles relating to efficiency and validity of research designs. Collection, management, and presentation of data utilize statistical concepts and techniques. Inference and prediction is the major role of statistics in medical research. Mathematical statistics is concerned with the theoretical aspects

E. RATIONALE OF LEARNING BIOSTATISTICS

Medicine is increasingly quantitative with many parameters of disease and health being measurable. Quantitative description using numbers is superior to qualitative description. Biostatistics provides the tools for the summary and digestion of a lot of numerical laboratory and clinical data. Medical research requires statistical methods in the design and analysis of studies. The statistician has become a major player in medical research and are not mere consultants called in from time to time. Any clams of benefits or efficacy of any new treatment is inherently un-ethical if not backed by valid statistical analysis (Tahir 2/99). Medical literature is full of statistics. Knowledge of bio-statistics is needed for critical reading and evaluation of published reports. Knowledge of bio-statistics is needed to discover misuse of statistics and avoid reaching wrong conclusions

1.4.2 HISTORY OF BIOSTATISTICS

A. ANCIENT TIMES:

The word statistics is from the Latin word for state, statum, which indicates that in earlier times this discipline had something to do with the state. Since very ancient times there was interest enumeration of the population for purposes of taxation and military preparation. Historical records show that the ancient Egyptians, Greeks, Romans and Incas had annual censuses. Military officials counted people to know the number of eligible young men for military service. Omar Ibn al Khattab started the population registers, dawawiin, which were population registers for military purposes and also for financial disbursements to families, children, and soldiers.

B. ERA OF VITAL RECORDS:

Churches have from time immemorial kept records of births, marriage, and baptism. State registration of marriages, baptisms, and deaths in England and Wales dates back to 1548. In 1748 a Swedish law required registration of baptisms, weddings, and deaths. An English law was promulgated in 1836 on registration of births, deaths, and marriages. In 1874 such registration was made compulsory. The first register of vital events was the 'Bills of Mortality’ in London in 1542. Registration of vital events is now universal.

In 1662 John Graunt published 'Natural and Political Observations Made Upon the Bills of Mortality". He is considered the founder of bio-statistics. He also laid the foundations of the science of demography. In his analysis, John Graunt made the following observations: phenomena of death and birth were regular, there were more male than female births, mortality was higher in the first years of life, urban deaths were more than rural deaths. In 1694 Edmund Halley (1658-1742) constructed the life table and computed life expectancy using vital data. William Farr was in charge of vital statistics in England and Wales for 40 years starting in 1849. He started the modern procedures of vital statistics registration. In 1840 he defined Infant Mortality Rate as number of infant deaths per 1000 of live births. William Furr and Jacob Marc d’Espino were invited in 1853 by the 1^st Statistical Congress held in Brussels to draw up a disease classification scheme, which later became the International Classification of Disease (ICD). Quetelet developed vital statistics in its modern form. Lemuel Shattuck of Boston published books on vital statistics in 1845 and 1850.

C. POPULATION STUDIES

The first complete census was carried out in Sweden in 1749, in the US in 1790, in Spain in 1798, in England and Wales in 1801, in Canada in 1871. Demography is an offshoot of vital statistics that has developed into an independent discipline. It deals with the analysis of population data and making projections for the future. In 1798 Rev Thomas Robert Multhus (1766-1834) published ‘The essay on the principle of population as it affects the future improvement of society’ in which he argued that population grew geometrically and food production grew arithmetically. He mentioned methods of controlling population growth such as late marriage and a high infant mortality. In 1822 Francis Plate (1771-1854) openly advocated birth control to check excessive population growth.

D. ERA OF DECRIPTIVE STATISTICS

Mathematical developments were an impetus to statistics. John Napier (1550-1617) devised the natural logarithms and Henry Briggs (1561-1630) adapted them for base 10.

Pierre Charles Alexandre Louis (1787-1872) introduced the numerical method in describing medical facts quantitatively. He published ‘Recherches anatomo-pathologiques sur la phthisie' in 1825 which was a detailed numerical description of 123 cases of tuberculosis. In 1829 he published a study of 138 cases of typhoid. He was interested in describing groups of patients and not individual patients. He had great influence on statisticians in Europe and America. In 1846 Adolph Quetelet used the concept of means as a center of gravity. The concept of the median was conceived in 1816 by KF Gauss but was independently rediscovered by GT ?Fecnher in 1874. In 1894 Karl Pearson (1857-1936) introduced the term mode. Karl Pearson introduced the term mean deviation. The term variance was introduced by Sir R.A. Fisher (1890-1962). Karl Pearson introduced the coefficient of variation in 1895. Karl Pearson developed the concept of moments around 1893. He introduced measures of symmetry and kurtosis in 1905. He introduced various terms to describe kurtosis: leptokurtic (sharp peak), mesokurtic (medium peak), platykurtic (flay peak), isokurtic (symmetric), and allokurtic (skewed). In the period 1869-1885, Sir Francis Galton developed the concepts of percentiles, quartiles, deciles and other quantiles. The concept of the semi inter-quartile range, Q₃- Q₁/2_, was introduced by L.A.S Quetelet (1796-1874) and Sir Francis Galton (1822-1911) named it the quartile deviation. In 1892 Karl Pearson (1857-1936) published ‘Grammar of Science’ and in 1901 he was responsible for founding the journal ‘Biometrika’ and edited it for 35 years. He coined the term ‘standard deviation’ and introduced its symbol as s in 1893. William Sealy Gosset (1876-1937) published a paper in 1908 introducing the student t test. The British statistician, Sir Ronald Aymer Fisher (1890- ) made many contributions to modern statistics. He developed methods for small samples. In 1935 he published ‘Design of Experiments’ in which he advocated factorial designs that worked well in agriculture but not so well in medical research. He used the term ‘statistic’ to refer to a sample estimate of a population parameter in 1925. In 1809, Karl Friedrich Gauss (1777-1855) discovered the normal distribution that has independently been discovered before in 1774 by Pierre Simon Marquis de Laplace (1749-1827) and in 1733 by Abraham de Moivre (1667-1754). In 1877 Sir Francis Galton used the adjective ‘normal’ to refer to the curve. W.F. Sheppard introduced the standard normal curve in 1899. C Kremp published the first table of the area under the curve in 1799.

The 19^th century CE witnessed major developments in statistics as a discipline and as a profession. In 1844 the Royal Statistical Society of London was organized. The American Statistical Association was formed in 1849. The US Bureau of the Census was established in 1902.

E. ERA OF ANALYTIC STATISTICS

ANALYTIC TECHNIQUES

Karl Pearson introduced the chi-square test sometimes referred to as Pearson’s chi-square. Sir Francis Galton applied statistical theory to the study of natural biological phenomena. In 1869 Sir Francis Galton (1822-1911) published his ‘Heredity Genius’ in which he applied statistical methods based on the normal curve and deviation from the mean. He also described correlation and regression. In 1889 he published In ‘Natural Inheritance’ including the correlation table and introduced the symbol r for correlation. RA Fisher introduced the concept of the null hypothesis. The symbol of the null hypothesis (H₀), type 1 and type 11 errors were introduced by Karl Pearson and J Neyman. The concept of confidence intervals was developed by J Neyman in 1934. RA Fisher introduced the concept of random allocation. He also introduced the concepts and techniques of analysis of variance (ANOVA). Analysis of covariance (ANCOVA) was introduced by RA Fisher. Sir Francis Galton discovered regression and correlation in the period 1875-1885. The least squares method was first published in 1805 by Adriene Marie Legenun (1752-1838) but Gauss claimed he had used it 10 years earlier. The method proved very useful in fitting regression models. An alternative to least squares was proposed in 1757 by Roger Joseph Bescovitch (1711-1787) under the name ‘least absolute deviation’ and was employed by Pierre Simon de Laplace. It however did not become popular because it was computationally more complicated than least squares. In 1923 RA Fisher described the relation between regression and analysis of variance. Karl Pearson described homoscedacity and heteroscedacity in regression in 1905. Fisher introduced use of the t test for testing the significance of the regression coefficient. Charles Spearman (1863-1945) and Maurice George Kendall (1907-1983) introduced non-parametric tests. In 1892 F Y Edheworth was the first to introduce the concept of correlation among more than 2 variables. In 1897 C V Yule was the first to use R for the multiple correlation coefficient. In 1897 Karl Pearson introduced the concept of partial correlation. Karl Pearson and RA Fisher have the credit for early development of contingency table analysis using the chi-square test.

The symbol for infinity was introduced by John Willis (1616-1703).

PROBABILITY and STATISTICAL THEORY

The bulk of statistical theory is probability theory since modern inferential statistics depends on probability theory. Christian Huygens (1629-1695) was the first one to publish on probability and games. Modern probability theory owes a lot to the pioneers: Blaise Pascal (1623-1662), Pierre de Fermat (1601-1665), Jacques Bernouilli (1654-1705), Nicolas Bernouilli (1687-1759), Abraham de Moivre (1667-1754), Pierre Remond de Montmart (1678-1719), Pierre Simon Marquis de Laplace (1749-1827).

Abraham de Moivre (1667-1754) published ‘The Doctrine of Chance’ in 1715 and ‘Annuities upon Lives’ in 1725. He had in 1733 discovered the normal curve but his work was overlooked; the curve was rediscovered by Pierre Simone Laplace and Karl Friedrich Gauss (1777-1855). Jacques Bernoulli introduced the term permutation in 1714. In 1714 Nicolas Bernoulli developed the theory of probability that was perfected by Laplace. In 1835 Lambert Adolphe Jacques Quetelet (1794-1874) published ‘On Man and the Development of His Faculties’ in 1835. In 1846 he published ‘lettres sur la probabilite’ and showed the application of the normal curve to biological measurements. Venn diagrams used in set theory and probability are named after the English logician John Venn (1834-1923).

1.4.3 LIMITATIONS OF BIOSTATISTICS

A. STATISTICAL VS SUBSTANTIVE:

An investigator starts with a substantive question. This is formulated as a statistical question. Data is then collected and is analyzed to answer the statistical question. The answer to the statistical question is the statistical conclusion. The investigator uses the statistical conclusion and other knowledge available to him to reach a substantive conclusion. Statistics therefore gives statistical and not substantive answers. A substantive question is the subject matter stated in ordinary language. Technical terminology may or may not be used. The less technical the formulation is, the better to enable statisticians who are not specialists in the subject matter can understand. Care must be taken to make sure that accuracy and exactness are not sacrificed for the sake of simplification. A statistical question is when the substantive question is stated using statistical language. Since the language of statistics is mathematical, the statistical question is stated as numbers, parameters, relations of equality, and relations of inequality. A statistical conclusion is the result of mathematical manipulation of parameters or data. Statistical conclusions are made about groups and not individuals. Any inference to the individual is to a hypothetical individual. In other words the statistical conclusion is depersonalized. A substantive conclusion is the translation of the statistical conclusion back to normal language to answer the substantive question that was posed at the start.

B. ANAYLSIS VS INTERPRETATION:

Statistical results are dry unless well interpreted and put in the right context. Bio-statistics only summarizes the data but does not interpret. Interpretation involves knowledge of the context, prior knowledge, and prior suppositions. Personal familiarity with the data may also influence how it is interpreted. Data that is well analyzed may be poorly interpreted

C. MISUSE OF STATISTICS:

Statistics is a tool that can be used well or badly. If misused, the blame should be on the user and not the tool. Mis-use of statistics can be deliberate deception or can be due to ignorance. Selective presentation of desired results while suppressing undesirable ones is one method of misuse of statistics. Sometimes the cart is put before the horse when the statistical methodology available determines what types of research questions are dealt with. The correct approach is to have research questions and select the suitable method.

D. MIS-USE OF THE COMPUTER:

Computation is not an end in itself. It is a tool that can be used well or can be mis-used. The computer itself has very little intelligence all it possesses is speed and memory. A human must have a clear idea of what is required of the computer and must instruct it accordingly. The human must also be able to intelligently interpret the output from the computer. All who tinker with computers must remember the adage ‘rubbish in/rubbish out’.

1.4.5 CAREER OPPORTUNITIES IN BIOSTATISTICS

A. PRACTICAL APPLICATIONS

Quantitative Research: The need for statistical work has been propelled by the growth of medical services, new drugs and new therapies & procedures. Bio-statistics enables us to move from intuition to objective conclusions. Both observational and experimental studies yield information and conclusions from statistical inference.

Administration: Statistical information is used in the planning of hospitals and other health facilities. Manpower and facilities can be projected using available statistical information.

Decision-making: decision-making has moved from being an intuitive and often unsystematic process to being a scientific discipline that yields accurate and consistent results. Decisions on clinical management, health expenditures, and population policy require statistical support.

B. TYPES OF STATISTICAL PRACTICE:

An amateur statistician is a person with a different career who learns enough statistics to be able to carry out his research work. A professional statistician works fully as a statistical consultant to researchers. Mathematical statisticians are engaged in development of statistical theory with special emphasis on probability theory

C. STATISTICS CAREERS IN THE UNIVERSITY

The main role of statisticians in the university setting is teaching combined with research. Their research can be in improvement of statistical techniques. It can also be in a supportive role for other researchers who require statistical consultation.

D. STATISTICAL CAREERS IN THE PUBLIC SECTOR

Statisticians work in the Ministry of Health and departments of statistics of various government ministries. They also work in specialized research institutions.

E. STATISTICAL CAREERS IN THE PRIVATE SECTOR

Drug companies, insurance companies, and hospitals employ biostatisticians. Those who work for drug manufacturing companies are involved in clinical trials of new drugs and devices. Statisticians working for insurance companies help compute the right insurance premiums based on life expectancy for different population groups. Hospitals need analysis of their outcome measures for planning and quality improvement purposes.

ILLUSTRATONS

Figure #1: Inter-relations between bio-statistics and epidemiology

Bio-statistics	Epidemiology
Descriptive statistics	descriptive epidemiology
Inferential statistics	analytic epidemiology
Clinical statistics	clinical epidemiology

EXERCISES: TRUE/FALSE QUESTIONS

1. The following statements are true about the discipline of biostatistics

Biostatistics deals with management and analysis of numerical data
Biostatistics is confined to study of human diseases only
Biostatistics does not include vital statistics
Biostatistics cannot be used in the analysis of demographic information
Biostatistics has 2 main branches: descriptive and inferential statistics

TFFFT

2. The following statements are true about the discipline of biostatistics

Bio-statistics has a mathematical foundation
Bio-statistics is purely quantitative with no qualitative aspects at all
Marriage statistics are not part of bio-statistics
Probability is the bulk of theoretical biostatistics
Biostatistics is a basic science in medicine

TFFFT

3. The following statements are true about the discipline of biostatistics

Statistics is a branch of applied mathematics
Statistics helps interpret numerical information
Biostatistics can be used in veterinary science
Biostatistics is not necessary for critical reading of medical literature
Biostatistics is useful in public health and not clinical medicine

TTTFF

4. Biostatistics is useful in the following roles

Design, execution, and analysis of experimental studies
Collection, management and presentation of data
Inference about association between and among variables
Administration of health services
Decision making

TTTTT

5. The following statements are true about statistical questions and conclusions

Substantive questions are framed as statistical questions for analysis
Statistical conclusions may differ from substantive conclusions because of bias
Statistical significance is exactly the same as clinical or practical significance
Some substantive questions cannot be answered statistically
A valid substantive conclusion can be from an invalid statistical conclusion

TTFTF

6. The following statements are true about statistical questions and conclusions

Bio-statistics always conclusively answers substantive questions
Substantive conclusions require interpretation
Statistical inference is mostly deductive
A statistical question is framed to be answered quantitatively
Data is not necessary in formulating a statistical conclusion

FTFTF

7. The following statements are true about pioneers of biostatistics

John Graunt analyzed the bills of mortality
William Furr was Registrar General of England and Wales
Sir A Fisher developed the exact tests
Quetelet had nothing to do with vital statistics
Poisson made no contributions to probability theory

TTTFF

8. The following statements are true about the history of biostatistics

Counting of the population was used in ancient civilizations for military purposes
John Graunt is considered the father of biostatistics
The first complete census was carried out in the US
William Furr developed the modern procedures of vital statistics
Bernoulli contributed to the development of the probability theory

TTTTT

9. The following are examples of descriptive statistics

Computation of death rates
Comparing the effectiveness of 2 treatments
Computation of percentage of immunized children
Tabulation of the leading causes of death
The relation between aedes mosquito and dengue fever

TFTTF

10. The following are examples of descriptive statistics

Determining the proportion of males in the population
Studying the relation between stress and peptic ulceration
Determining the birth rate
Determining the death rate due to tuberculosis
Identifying causes of chronic obstructive pulmonary disease (COPD)

TFTTF

11. The following are examples of inferential statistics

Determining the relation between smoking and lung cancer
Geographical distribution of malaria
Sex and age distribution of AIDS patients
Proportion of citizens who smoke cigars
The relation between stress and PU

TFFFT

12. The following are examples of inferential statistics

Survival of several groups of patients under different treatments
Public opinion polling to predict outcome of an election
Survey for presence of hypertension in a community
Evaluating the effectiveness of a contraceptive
Determining the percentage of lung cancer due to cigarette smoking

TTFTT

13. Biostatistics has the following limitations

It gives statistical and not substantive answers
The statistical conclusion refers to groups and not individuals
Bio-statistics only summarizes the data but does not interpret
Human intellect is needed to interpret statistical analyzes
Results of computer analysis of data are always valid and reliable

TTTTF

EXERCISES: COMPUTATIONS

1. Compute 4/7 using a hand-calculator and a computer to 1,4,5 and 10 places of decimal. Comment on the difference between calculator and computer results

2. Compute the average of the following integers using three methods: (a) manually (b) by hand calculator (c) by computer. Comment on the difference in the speed of the operations. The integers are: 5,9,8,10,11,12.

EXERCISES: JOURNAL STUDY

Using the internet to find information about the history of bio-statistics as an independent discipline

3. Using the internet find out the history of population censuses

4. Using the Internet find brief biographies and contributions of the following pioneers of bio-statistics: Fisher, John Graunt, William Farr, Quetelet, La Place, and Bernoulli.

5. Review the abstract and methodology sections of 5 articles in a current issue of any medical journal and draw a table showing the frequency with which the following statistical terms are used: t-test, chi-square test, linear regression, logistic regression, analysis of variance, p-value.

6. Use the reference library to list statistical packages or programs that are used for (a) data management (b) data analysis (c) both data management and data analysis

7. Find out and describe the following information about a computer: Random access memory, hard disk memory, speed, type of chip used, byte, bit, local area network, server

EXERCISES: PROBLEM-SOLVING

EXERCISES: PRACTICAL ASSIGNMENTS:

1. Prepare a mailed questionnaire and collect the following data on members of the class:

· Identifying information: ID (not real), gender, year of study

· Sociodemographic information: home address (urban/rural), region of origin (East Coast, West Coast & Central, North, South, Other), primary school (religious, private, public)

· Family information: number of siblings, paternal grandfather living now? (yes/no) and if dead age at death

· Wearing glasses for refractive errors (yes/no), age at which glasses were first prescribed, does the father wear glasses (yes/no), does the mother wear glasses (yes/no), does any sibling wear glasses (yes/no)

2. Prepare a questionnaire for face to face interview to collect the following information on opinions and preferences

· Color preference (choose one color only)

· Desire to specialize or work as a general practitioner (yes/no)

3. Prepare a computer administered questionnaire to collect the following information

· Ideal age for marriage

· Desired number of children

4. Prepare a telephone administered questionnaire with items to assess personality as either type A or type B. Select a random sample of 10 students in the class, obtain their personal telephone numbers. Arrange to have two interviewers to interview a subject separately. Each must at the end of the interview assign the interview subject to either type A or type B personality types.

5. Carry out a case control study as follows. Select all students who wear glasses as ‘cases’. Then select a random sample of equal size from the class. Prepare a questionnaire for both groups asking for whether parents or siblings in the family use glasses. Include the following additional questions about potential confounders: father’s occupation, mother’s occupation, type of school, any routine vision tests at primary school

6. Carry out a follow-up study as follows. Distribute a guide to a sample of 20 students on how to wake up more energetic in the morning by exercising for 2 minutes and/or reading specific surahs from the Qur’an before going to bed. You need not give them any specific instructions to read the guidelines or put them in practice. Distribute a questionnaire the next morning asking them about exercising, Qur’an recitation, and energy on waking up.

7. Carry out the following community intervention study. Randomly allocate the housing blocks in the student hostel to the experimental and control groups such that there are equal numbers of blocks in each group. Prepare a pre-intervention questionnaire to ascertain KAP on drinking sufficient amounts of water. Then provide written information about the recommended daily water intake. Administer a post intervention questionnaire on KAP after 2-3 days.

8. Carry out the following clinical intervention study. Ask for 20 volunteers and obtain a nasal swab from each one of them. Then allocate each one of them randomly to either the experimental or the control group. Give the experimental group instructions to rinse their nose 10 times at wudhu for each salat. No specific instructions should be given to the control group. Take a nasal swab from both groups after 3 days. Ask the microbiology laboratory to culture bacteria from the pre and post intervention swabs. Consult with them on how best to quantify the amount of bacteria in the nasal swabs.

9. Carry out the following clinical intervention study. Obtain a sample of 20 students and give them a questionnaire with items on the Friday (end-of-week) burnout syndrome. Then allocate them randomly to experimental and control groups such that each group has an equal number of subjects. Advise the experimental group to take 1 multivitamin tablet with each of their meals starting Wednesday through Sunday. The control group should be advised not to take any vitamins. Administer a questionnaire on Monday morning about their 4 levels of feeling energetic: very energetic, energetic, no change, fair, worse

10. Carry out the following measurements/observations on all members of the class using standard procedures

· Blood pressure sitting down and lying supine

· Pulse rate before and after light exercise (stationary jogging for 3-5 minutes)

11. Carry out the following exercise on reading speed

· Type the following text on the computer and using 4 font sizes (9, 11, and 14) and print types (Arial and Times New Roman).

· Divide the class into three reading teams according to the type of primary school that they attended (private, national, or agama)

· Each team should have only 10 persons. Record the time (in minutes and seconds) it takes each individual member of the team to read the text using various font sizes and print types.

12. Carry out the following exercise on persistence of a taste sensation

(a) Divide the class into 2 teams and use a fixed measure of salt or sugar placed at the tip of the tongue to test the sense of taste. When the test substance is put at the tip of the tongue a stopwatch is used to measure how long it takes for the taste to disappear completely.

(b) The experiment is terminated automatically at the end of 2 minutes. It will also be terminated if any person either voluntarily or involuntarily withdraws their tongue into the mouth for swallowing. Record the time when this occurs.

UNIT 1.5

INTRODUCTION TO COMPUTING

Learning Objectives

· Understanding the information revolution and its impact on medicine

· Understanding basic computer technology

· Limitations and ethics of information

Key Words and Terms

· Artificial Intelligence

· Bit

· Byte

· Central processing unit

· Computer hardware

· Computer language

· Computer Programs

· Computer Security

· Computer software

· Computer, mainframe

· Computer, minicomputer

· Computer, personal computer

· Computer, supercomputer

· Computer-assisted Decisions

· Computing Methodology

· Data dictionary

· Data set

· Database, hierarchical database

· Database, network database

· Database, relational database

· Information Retrieval

· Information Science

· Information Storage

· Information Systems

· Input device

· Internet

· Mathematical Computing

· Mathematical Statistics

· Medical Informatics

· Modem

· Network, Local Area Network

· Network, Metro Area Network

· Network, Wide Area Network

· Numerical Analysis

· Output device

· RAM

· Robotics

· Systems analysis

UNIT SYNOPSIS

1.5.1 INFORMATION REVOLUTION AND THE COMPUTER AGE:

Data is used for operational, managerial and planning functions. Use of computers is facilitated by routine computerization of operational data. The invention of the computer enabling humans to handle large amounts of data has created an information revolution. New computers can manage (collection & storage) and analyze large amounts of data, a feat that was unthinkable a few years ago. The growth of computational techniques has enabled deeper and more sophisticated analyses. Availability of high speed and efficient computing has encouraged growth in statistical methodology and more sophisticated statistical analysis. This has in turn called for developments in statistical theory that is later translated into newer and more powerful analysis programs.

1.5.2 INFORMATION SYSTEM

An information system has 5 components: people, procedures software, hardware, and data. Database management systems (DBS) create, modify, and access data. Data elements are arrayed to make a record or an observation. Files are made up of several observations. Several files make a database. A data dictionary describes the structure of the data. A relational database is in the form of a table with rows and columns in the form of one-to-one. A hierarchical database is several layers of information in the form of one-to-many. A network database is a many-to-many architecture. A program is a series of instructions that the computer executes. Computer languages are at various levels of sophistication. Machine language and assembly language are in binary code. High level procedural languages are BASIC, Pascal, C, COBOL, and FORTRAN. Problem oriented languages are query languages used in searching databases. Natural language is usual human language that the computer cannot use directly. Ethical issues of privacy, accuracy, data ownership, data access, and security arise due to the large amount of personal information now kept on computers.

1.5.3 HISTORY OF COMPUTING

The Chinese discovered the abacus for making arithmetic computations easier. In 1882 John Shaw Billings invented the Hollerith punched card for processing US census results. The Electronic Numerical Integrator and Calculator (ENIAC) was invented after World War II for ballistic calculations. The Digital computer company developed the first personal computer in 1965. The development of personal computers was the real computer revolution because it led to widespread availability of computers in homes and offices. This increased access of ordinary people to computing.

1.5.4 COMPUTER HARDWARE DEVELOPMENTS:

Computer can be microcomputers, minicomputers, mainframe computers, and supercomputers. Computer hardware consists of input devices, a central processor, output devices, and communication devices such as the modem. The central processing unit (CPU) is the calculating part of the computer. Data is stored as binary units (bits) either 0 or 1. Eight bits make a byte. A KB is 1024 bytes, MB is 10⁶bytes, GN is 1 billion bytes, and TB is 1 trillion bytes. Data in a computer is stored as files (sequential or random access) that are grouped in directories. RAM keeps data during the processing stage. Long-term memory is the hard disk, floppy disk, or CD-ROM. The modem is used to transfer data from one point to another. Communication channels can be telephone lines, co-axial cables, fiber optic cables, and microwaves. Microwaves operate over short distances and require satellites as relay stations. Computers may be interconnected in a local area network, LAN; a metro area network, MAN; or a wide area network, WAN. Ergonomic designs are used to avoid health problems due to working at computer workstations for long hours.

1.5.5 COMPUTER SOFTWARE:

Software consists of the operating system and the application programs. A statistical package is a collection of programs. There are three types of software: operating systems such as windows, general-purpose programs such as word processors and statistical packages, and futuristic programs. The most popular statistical packages are BMDP, SPSS, Minitab, Censtat, SAS, and GLIM. Epi-info and Egres are specific for epidemiology. Specialized programs may be graphics, communication, multimedia, and futuristic programs. Artificial intelligence is an attempt to simulate human thought and actions used in robotics, expert systems, and virtual reality. Knowledge-based or expert systems are programs that incorporate the human thought or problem-solving processes. Virtual reality, also called artificial reality or virtual environment, is used in entertainment and simulators that train aircraft pilots.

UNIT OUTLINE

1.5.1 INFORMATION REVOLUTION AND COMPUTER AGE:

A. Increased Generation and Use of Data

B. Storage of Large Data Sets

C. Processing Of Large Data Sets

D. Development of Statistical Methodology:

E. Development of Statistical Theory

1.5.2 INFORMATION SYSTEM

A. Components of an Information System

B. Database Management Systems

C. System Analysis and Design

D. Computer Programming

E. Ethical Problems

1.5.3 HISTORY OF COMPUTING

A. Ancient times

B. Earliest computing machine

C. The first computer

D. Mainframe and minicomputers

E. Personal computers

1.5.4 COMPUTER HARDWARE DEVELOPMENTS:

A. Types of Computers

B. Input and Output Devices

C. Central Processing Unit

D. Connectivity

E. Ergonomics

1.5.5 COMPUTER SOFTWARE:

A. Definition and Types of Software

B. Operating Systems

C. General Purpose Programs

D. Specialized Programs

E. Artificial Intelligence

1.5.1 INFORMATION REVOLUTION AND COMPUTER AGE:

A. INCREASED GENERATION AND USE OF DATA

All organizations generate and use a lot of data. Many managerial and planning functions are based on information in the database. A lot of data operational is generated. For example a hospital schedules a lot appointments and surgery. There is a lot of billing and financial data. A lot of this data is now computerized. Use of computers is facilitated by that fact that operational data (from hospitals and vital records) is already computerized.

B. STORAGE OF LARGE DATA SETS

The invention of the computer enabling humans to handle large amounts of data has created an information revolution. New computers can manage (collection & storage) and analyze large amounts of data, a feat that was unthinkable a few years ago.

C. PROCESSING OF LARGE DATA SETS

Statisticians could handle little data before the development of rapid computing. They were able to do a bit more when hand calculators were available. The calculators however could not store or manage large data sets. Computers that are in essence programmable calculators that in addition are able to store and manage massive amounts of data superseded hand calculators. The growth of computational techniques enabled deeper and more sophisticated analyses. More powerful computers with more sophisticated statistical packages are now available.

D. DEVELOPMENT OF STATISTICAL METHODOLOGY:

Availability of high speed and efficient computing has encouraged growth in statistical methodology that was un-thought of before. Procedures that were rare are now carried out routinely. Statisticians in the past used to rely on approximate methods because exact methods were computationally difficult. Modern computers can complete the most complicated exact computations in a fraction of a second. Procedures that required repeated iterations before finding the right value could not be carried out before but are now routine thanks to the fast computers now available.

E. DEVEOPMENT OF STATISTICAL THEORY

The increased availability of computing power has encouraged the developed of more sophisticated statistical analysis. This has in turn called for developments in statistical theory that is later translated into newer and more powerful analysis programs.

1.5.2 INFORMATION SYSTEM

A. COMPONENTS OF AN INFORMATION SYSTEM

An information system has 5 components: people, procedures for example computer manuals, software (system software or applications software either custom-made or packaged), hardware, and data.

B. DATABASE MANAGEMENT SYSTEMS

Database management systems create. Modify, and access data. Database management systems serve the following purposes: sharing data, security of data by use of passwords, fewer files, and data integrity. The database management system has an element as basic building block. Several element values are arrayed as a single observation or record belonging to say one person. Several observations are put together to make a rectangular file showing values of variables for several individuals. Several files make a database. A data dictionary describes the structure of the data. Several types of databases can be identified depending in the architecture of information storage in the computer. A relational database is one in which all fields are related by the identifying variable. It is in the form of a table with rows and columns. A hierarchical database is several layers of information such that lower layers are not reached before higher ones are opened. The hierarchical database is a one-to-many arrangement. There are parent and child nodes. In searching for an item you start at the top and go deep into the data. A network database is a many-to-many architecture. An item can be reached in more than one way.

C. SYSTEM ANALYSIS AND DESIGN

The following are the various functions of a system analyst: system analysis, system design, system development, system implementation, and system maintenance. The setting up of a database or a transactional computer system is a highly intellectual exercise that requires full understanding of all operations of the organization, the routine and the exceptional ones.

D. COMPUTER PROGRAMMING

A program is a series of instructions that the computer executes. There are 6 steps in programming: program specification which states the objectives, the input and the output; program design which indicates the logic structure by means of flow charts to show all steps from input through processing to output; coding is the actual writing of the program at the computer terminal using a programming language; program testing or debugging is correction of syntax and logic errors; documentation is stating the purpose and process of the program; and program maintenance is development and improvement. Software engineering tools help produce more efficient programs. There are 5 generations of programming languages. Machine language is the binary code. Assembly language is still in binary code but is more readable than machine language. High level procedural languages like BASIC, Pascal, C, COBOL, and FORTRAN are source codes converted by the machine into machine language (also called object code). Problem oriented languages are query languages used in searching databases. Natural language is usual human language.

E. ETHICAL PROBLEMS

Ethical issues of privacy, accuracy, data ownership, data access, and security arise due to the large amount of personal information now kept on computers. Computer hackers who gain entrance to databases and cause havoc commit computer crimes. Viruses attack and destroy databases. Encryption is used to decrease the chance of stealing data in transit. Restriction of access using passwords also helps keep away intruders.

1.5.3 HISTORY OF COMPUTING

A. ANCIENT TIMES

Humans since time immemorial have used some devices for storing data and making simple computations. A herdsman would for example collect and keep one stone for each sheep that he had. He would add more stones to the collection as more sheep were born. He would also drop some stones if some of the sheep died or were lost. Some would tie knots on their cloth or on a string with each knot representing either one quantity or several quantities. The Chinese discovered the abacus for making arithmetic computations easier. It is still used in parts of China and other parts of the world. Other civilizations developed similar computing devices.

B. EARLIEST COMPUTING MACHINE

The history of computing reads like a fairy tale. Developments have been very rapid. In 1882 John Shaw Billings invented the Hollerith punched card for processing US census results. The Hollerith Company later became the famous International Business Machines (IBM).

C. THE FIRST COMPUTER

The Electronic Numerical Integrator and Calculator (ENIAC) were invented after World War II for ballistic calculations. It had 17,000 vacuum tubes and used an amount of electricity sufficient to 175 houses. The pace of development is such that today’s desktop PC is faster that ENIAC. ENIAC is the dinosaur of the computer revolution.

D. MAINFRAME and MINICOMPUTERS

The first computers were big structures available only in the largest institutions. In 1963 The National Medical Laboratory (NLM) developed Medlars/Medline and moved it to an IBM360 computer in 1965.

E. PERSONAL COMPUTERS

Digital developed the first personal computer called PD98 in 1965. The development of personal computers was the real computer revolution because it led to widespread availability of computers in homes and offices. This increased access of ordinary people to computing.

1.5.4 COMPUTER HARDWARE DEVELOPMENTS:

A. TYPES OF COMPUTERS

Computers come in various sizes and grades of complexity: microcomputers, minicomputers, mainframe computers, and supercomputers. Microcomputers are either desktop or portable. The Portable ones are laptops, notebooks, sub-notebooks, and the personal digital assistant. Computer hardware has the following components: (a) input devices: keyboard and mouse (b) system unit which consists of the central processing unit and the memory (random access or secondary storage). (c) Output devices: the monitor or video display screen and the printer. (d) Communication devices such as the modem. The trend of downsizing will continue. The electronics industry will pack more computing power in increasingly smaller units. The range of applications will broaden. Pen-based computing will become possible.

B. INPUT and OUTPUT DEVICES

INPUT DEVICES

Character input devices are of two types: keyboard and direct. The keyboard has three types of keys: typewriter keys, functional keys, and numeric keys. There are several direct input devices: the mouse, the touch screen, the light pen, the image scanner, the barcode reader, the magnetic link recognition as is used in bank or smart cards, and optical mark recognition. Voice input devices can either recognize continuous speech or discrete words

OUTPUT DEVICES

There are three types of character output devices: monitors, printers, and plotters. Monitors can be VGA, SUGA, and XGA. They may come in a standard form, as desktop, and as portable monitors. HDV monitors have started appearing. Printers can be dot matrix, inkjet, laser, or thermal. Voice output devices enable a computer to pronounce a printed word.

C. CENTRAL PROCESSING UNIT

THE COMPUTER CHIP

The central processing unit (CPU) is the calculating part of the computer. The CPU in a personal computer is a single electronic component called the microprocessor chip. The chip is the control unit that tells the computer how to carry out a program’s instructions. The arithmetic logic unit carries out arithmetic operations such as addition, subtraction, division, and multiplication. It also carries out logical operations like inequalities, < or < and the equality =. Data is stored as binary units either 0 or 1. Each ‘0’ or ‘1’ in the binary system is called a bit. Eight bits are combined to make a byte. A kilobyte, abbreviated as KB or K-byte, is equivalent to 1024 bytes. A megabyte, abbreviated as MB pr M-byte, is 10⁶bytes. A Gigabyte, abbreviated a BG or G-byte, is 1 billion bytes. A terabyte, abbreviated as TB or T-byte, is 1 trillion bytes. There are 4 types of random access memory: conventional is up to 640 KB, upper memory 640KB to 1 MB, extended memory is over 1 MB, and expanded memory. Some memory is read only ROM.

FILE STORAGE and RETRIEVAL IN THE COMPUTER

Data in a computer is stored as files that are grouped in directories. The files may be arranged sequentially or may be accessed randomly. In the sequential arrangement, records are stored physically one after the other. In random access any record is directly accessible. The index file is a compromise between the two extremes. Each file in turn consists of records that may be in a fixed format or a free format. If the format is free there is need for instructions to enable correct reading and separation of the variables. Files may be master files containing permanent data or transaction files. Query languages are used to access data. They use commands such as display, add, compare, list, select, update.

COMPUTER MEMORY

The random access memory keeps data during the processing stage. The memory is either random access memory (RAM) or secondary storage. Secondary storage or long-term memory is either or the hard disk or some form of external storage such as floppy disks, optical disks, magnetic tape, and the compact disk. The hard disk may be an internal hard disk, a hard disk cartridge, or a hard disk pack. The compact disk may be read only CD-ROM or may be recordable, CD-R.

D. CONNECTIVITY

There are many ways of connection between information centers: fax machines, electronic bulletin boards for messaging, electronic mail, voice messaging, shared resources by uploading or downloading, and online services. The modem is an acronym for modulator-demodulator. It is used to transfer data from one point to another. Modem speed is measured in bits/second. Modems come in various forms: external modems, internal modems, wireless modems, and fax modems.

The communication channels between and among computers can be telephone lines, co-axial cables, fiber optic cables, and microwaves over short distances, and satellites as relay stations for microwaves. Computers may be interconnected in a local area network, LAN; a metro area network, MAN; or a wide area network, WAN.

E. ERGONOMICS

Many people spend a big portion of the working day sitting at a computer terminal that leads to physical and mental stress. The physical problems are eyestrain that causes headache, back and neck pain, repetitive injury of the wrist and fingers, and the effects of the electromagnetic radiation from the screen. Noise and excessive monitoring lead to mental stress.

1.5.5 COMPUTER SOFTWARE:

A. DEFINITION and TYPES OF SOFTWARE

The software is the operating system and the application programs. The programs are written in several computer languages (basic, FORTRAN, C, and Pascal). A program sets out the statistical method step by step. A statistical package is a collection of programs. There are three types of software: operating systems, general-purpose programs, and futuristic programs.

B. OPERATING SYSTEMS

Operating systems are DOS, Windows, OS/2, Macintosh, and UNIX.

C. GENERAL PURPOSE PROGRAMS

General-purpose programs are word-processing, database management, statistical software, spreadsheets, graphics software, communication software. The following are the most popular statistical packages and the years of their introduction: BMDP in 1961, SPSS in 1970, Minitab in 1972, Censtat in 1972, SAS in 1972, and GLIM in 1974. Epi-info and Egres are specific for epidemiology. SAS first appeared in ?1976 and was available on PCs in the 1980s. Epi-info was released in 1985.

D. SPECIALIZED PROGRAMS

GRAPHICS SOFTWARE

Graphics software is of three types: analytic graphics, presentation graphics, and drawing programs.

COMMUNICATION SOFTWARE

Allows access and exchange of information.

MULTIMEDIA

Games are a type of multi or hyper media

FUTURISTIC PROGRAMS

These are already available are: the personal information manager, groupware coordinating people, project management software, desktop publishing, and multimedia.

E. ARTIFICIAL INTELLIGENCE

Artificial intelligence is an attempt to simulate human thought and actions. Artificial intelligence is used in three areas: robotics, expert systems, and virtual reality.

Robotics may be industrial doing repetitive jobs that humans find boring. Some robotics are perceptive with sensory functions. Other robotics are mobile and are used in various ways including recreation.

Knowledge-based or expert systems are programs that incorporate the human thought or problem-solving processes. They use human logic in problem solving and follow probability rules using probability trees. Artificial intelligence programs search systematically for a solution by looking through many alternatives and choosing the best. The best programs are those that are able to focus on the more plausible alternatives. These programs require a knowledge base. They work by first reducing a big problem into smaller more manageable problems. The problem may be restated in another way to make the solution easier.

Virtual reality is also called artificial reality or virtual environment is used in entertainment and simulators that train pilots.

ILLUSTRATIONS

EXERCISES: TRUE/FALSE QUESTIONS

1. The following statements are true about an information system

3. People are not an important component of the system

4. Software is a term used to refer to computer programs

5. Hardware is a term used to refer to the more complex computer procedures

6. Information systems are needed for management

7. Planning does not rely on information systems

FTFTF

2. The following statements are true about data bases

A database management system has the function of creating data
A database management system has the function of modifying data
A database management system has the function of accessing data
A record or observation refers to all information about one individual
A file contains only 1 record

TTTTF

3. The following statements are true about data bases

Several files constitute a data base
A data base must always be big in any case not less than 1 MB
A relational database has rows and columns
A hierarchical database has several layers of information
A hierarchical database is described as one to many

TFTTT

4. The following statements are true about data bases

A. Access to a record is easier in the hierarchical than in a relational data base

B. A network data base is complex and is described as many to many

C. Records in a relational database are accessed using an identification number

D. Networks of databases are vulnerable to security breaches

E. Databases in a network can only be connected using the internet

TTTTF

5. The following statements are true about computer languages

Machine language is in binary code only
Assembly language is sophisticated and is therefore not in binary code
BASIC and Pascal are examples of machine languages
COBOL and FORTRAN are examples of high level procedural languages
Natural human language is not exact enough for computer programming

TFFTT

6. The following statements are true about ethics of databases

Information about individuals that is not criminal can be revealed to anybody
Patients give up their rights to privacy when they agree to be treated by physicians
Data in hospital databases is the property of the government
Computer security prevents access of unauthorized persons to personal data
Encryption protects data confidentiality during data transfer

FFTTT

7. The following statements are true about computer hardware

Microcomputers are desktop or laptop computers
The keyboard and the mouse are input devices
The printer is not considered an output device
All modems have the same standard speed of data transfer
The CPU is the ‘brain’ of the computer

TTFFT

8. The following statements are true about data storage

A byte is either ‘1’ or ‘0’
A kilobyte is 1000 bytes
A megabyte is a million bytes
A gigabyte is 1 trillion bytes
Data in computers is stored as files that are grouped in directories

FTTTT

9. The following statements are true about computer memory

RAM is temporary memory that keeps data during computations
A CD-ROM is a type of long term memory
A hard disk is always external to the computer
Long term memory cannot be expanded
RAM can be expanded

TTFFT

10. The following statements are true about data transfer

The modem is used to transfer data from one point to another
Data can be transferred using telephone lines
Co axial or fiber-optic cables are never used in modern data transfer
Satellites can be used in data transfer
LAN refers to a local area network

TTFTT

11. The following statements are true about computer software

Microsoft word is considered an operating system program
EXCEL is considered an application program
BMDP is a statistical package
SAS is a word processing program
SPSS is a statistical package

FTTFT

EXERCISES: COMPUTATIONS

EXERCISES: JOURNAL STUDY

Using the internet of online databases identify and summarize

1. One article on the information revolution and its impact on medicine

2. One articles on artificial intelligence

3. One article on computer-based diagnosis

EXERCISES: PRACTICAL ASSIGNMENTS

1. Organize the class data as a relational database

2. Organize the class data as a hierarchical database

3. Organize the class data as a network database.

Integrated Medical Education Resources

111018P - INTRODUCTION TO DISCIPLINES MODULE 1.0

MODULE 1.0

INTRODUCTION TO GENERAL EPIDEMIOLOGY

UNIT OUTLINE

1.1.1 DEFINITION, SCOPE, and CLASSIFICATION

Learning Objectives

Key Words and Terms

· Community medicine

D. The Renaissance and Age of Exploration (1500-1700 CE)

D. THE RENAISSANCE AND AGE OF EXPLORATION (1500-1700 CE)

Learning Objectives

Key Words and Terms

Learning Objectives

Key Words and Terms

A. COMPONENTS OF AN INFORMATION SYSTEM

A. ANCIENT TIMES

B. EARLIEST COMPUTING MACHINE