220113P - INFERENTIAL STATISTICS FOR DISCRETE DATA

Presented at the Research Methodology Winter Camp of AlMaarefa University on January 13, 2022 at 10.00am. By Professor Omar Hasan Kasule Sr. MB ChB (MUK), MPH (Harvard), DrPH (Harvard) Professor of Epidemiology and Bioethics

INTRODUCTION:

• The inference is drawing conclusions on the relation between the independent and dependent variables.
• Inference on discrete data is based on the binomial/multinomial distribution.
• The analysis is essentially a comparison of proportions between 2 groups or among several groups.
• There are more advanced methods not based on proportions that are covered by more advanced courses.

STATISTIC USED:

• It uses 2 approximate methods (z-statistic and the chi-square) used for large samples and one exact method (Fisher's Exact Method) used for small samples.
• Approximate methods are accurate for large samples and are inaccurate for small samples.
• There is nothing to prevent exact methods from being used for large samples.
• The commonest method is the chi-square method and is the one we shall describe.

STEPS:

• State the null and alternative hypotheses in terms of proportions.
• Ascertain the normal distribution of the data, equality of variances of sample proportions being compared, and adequacy of the sample size.
• The data is laid out in contingency tables and is inspected manually before the application of statistical tests.
• Use technology (SPSS) to compute the chi-square and derive the p-value.
• P <0.05 reject the null hypothesis
• P>0.05 do not reject the null hypothesis

SPSS PRINTOUT OF THE ANALYSIS OF THE RELATION BETWEEN GENDER and WEARING GLASSES:

 

  

220117P - HOW TO PUBLISH YOUR PAPER

Presented at a postgraduate research workshop at King Fahad Medical City Riyadh on January 17, 2022 11.30am-12.10pm by Omar Hasan Kasule Sr Professor of Epidemiology and Bioethics MB ChB (MUK), MPH (Harvard), DrPH (Harvard).

CHOOSE THE JOURNAL

• Success in publication is based on a correct matching to the journal
• Aim at high-impact journals if your research was original, rigorous, and has substantial detail.
• Keep the journal in mind even during the research. Do not start writing unless you have a journal in mind with alternatives
• Check the background of the journal including websites of predatory journals
• Read published articles in the chosen journal to make sure they are similar to what you plan to submit

CHECK YOUR MANUSCRIPT CAREFULLY

• Review the journal’s instructions to authors and follow them word by word
• Use margins and line spacings that the journal instructs
• Start each section of the manuscript on a new page
• All pages are numbered
• Figured and legends are grouped on separate page(s) at the back of the manuscript. Some journals ask you to put them in the text
• Make sure you follow word or page limits and also submit the acceptable number of illustrations. They must be of the quality accepted by the paper.

CHECK FOR GRAMMAR AND SPELLING MISTAKES

• Use spelling and grammar checkers but treat them as alerts sometimes they mislead you
• Spell checkers do not pick up a wrong word correctly spelled
• Spell checkers do not pick up missing words
• Having someone who did not see the manuscript before read through his fresh eye may see mistakes you missed
• Read the manuscript loud to yourself

SUBMISSION PROCESS

• Most submissions use online systems which allow you to track the progress of the paper
• Make sure you have correctly uploaded the last version of the manuscript and have uploaded the illustrations
• The online submission system may ask for additional information if it does not have the information included in the cover letter
• The cover letter from the corresponding author provides context for the paper. It should mention that the paper is original and has not been submitted to any other journal
• The cover letter should confirm that all authors contributed and may describe the contribution of each one
• Make sure you get a confirmation of receipt

HOW TO HANDLE EDITORS

• Distinguish between the roles of the editor and the managing editor and know how to deal with each one
• An editor is a volunteer scientist who accepts or rejects the manuscript. He also chooses the peer reviewers
• The managing editor is a full-time paid manager in charge of administrative details
• The manuscript editor checks your manuscript for consistency with the journal’s policies. He corrects grammar and spellings and may send you queries to clarify
• Respond promptly and politely to all editor queries. Do not start a fight with them. Do not try to prove you were right. Just do what they want. If they ask for something you already submitted just resubmit it

 

THE REVIEW PROCESS

• You must understand the review process to avoid making mistakes
• The editor makes an initial assessment: is the subject matter of interest to the journal? Is the manuscript complete? Does it follow the editorial style of the journal?
• The editor decides which manuscripts shall be sent to peer review and which ones shall be rejected outright
• The editor chooses 2 or more peer reviewers
• The review process is double-blind; both authors and reviewers are blinded
• Reviewer comments help the author even if the article is not accepted

DEALING WITH THE EDITOR’S DECISIONS

• If all reviewers are unanimous the editor’s decision is easy.
• If reviewers disagree the editor chooses an additional reviewer
• The editor’s decision is to accept, reject or modify. In good journals few papers are accepted as submitted there are always some revisions, minor or major. The rejected and modify letters are accompanied by the reviewers’ comments. Rejections are not all of the same degree: major flaws, can be revised, good but not competitive
• Do not fear contacting the editor about the decision. They are not enemies. They are on your side

 

RESPONDING TO THE EDITOR

• In your response rewrite the manuscript to include all criticisms you can reasonably accept and clarify points that were misunderstood by the reviewers. Make it easy for the editor to see where you made changes by using markup
• Attach a letter itemizing all you did. Your rebuttal of reviewer comments should not be antagonistic. If the comments were numbered follow the same numbers in your response
• You may resubmit the corrected manuscript to the journal that rejected it or you may submit it to another journal
• Try to meet the resubmission deadlines
• Follow up with the journal if you hear nothing within 8 weeks

HOW TO DEAL WITH PROOFS

• The copy editor corrects spellings and punctuations, checks abbreviations and units of measure, and revises writing to improve readability
• The copy editor may send queries
• You approve the final version. Check the proofs carefully. First read then study. Reading the proof backward is a sure way of detecting errors. The typesetting process may introduce errors you did not make
• You need to know how to mark the corrections for the typesetter to fix or if you agree you can correct them straightaway. Return proofs before the expiry of the deadline.
• Do not make additions to proofs
• You can add new references with the journal’s permission
• Check that all illustrations are present and are complete

PUBLICISING YOUR PAPER

• Use social media
• ORCID
• ResearchGate 

220118P - EPIDEMIOLOGY: ETHICAL AND PROFESSIONAL ISSUES

Presentation at a KFMC Nursing Diploma Program Epidemiology: Ethics in Research Held at King Fahad Medical City, Riyadh on 18 January 2022. By Professor Omar Hasan Kasule Sr. Mb Chb (Muk). MPH (Harvard), DrPh (Harvard) Professor of Epidemiology and Bioethics

 

MEDICAL ETHICS FRAMEWORK

• Autonomy = respect for individual rights
• Beneficence = Do good
• Non-maleficence = do not harm

ETHICAL ISSUES IN EPIDEMIOLOGY

• Review and approval of the research proposal by IRB.
• Respect participant's right to autonomy: Respect participant autonomy by obtaining 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.
• Respect participant rights to protection and welfare: Protecting the welfare of the participant by minimizing risk and establishing the right balance between individual and societal benefit. Protecting the privacy and confidentiality of participants.
• Balance risks vs benefits: Public health interventions carry risks and costs that must be balanced against the benefits.

PROFESSIONAL ISSUES IN EPIDEMIOLOGY

• Interpret and communicate study findings to the public (for self-protection) and policymakers.
• Avoid conflict of interest (COI)
• Follow the Code of conduct for epidemiologists

ETHICAL APPROVAL

• A study involving humans must get approval from a recognized body in our case the Institutional Review Board (IRB).
• For approval, the study must be scientifically valid. It is unethical to waste resources (time and money) on a study that will give invalid conclusions.
• In 1991 the Council for International Organizations of the Medical Sciences published ‘International Guidelines for Ethical Review of Epidemiological Studies’^[1]: consent, maximize benefit, minimize harm, confidentiality, and conflict of interest.

PARTICIPANT RIGHTS 1: INVESTIGATOR'S OBLIGATION TO STUDY SUBJECTS^[2]

• Informed consent and after full disclosure
• Protecting privacy and confidentiality. Access to data.
• Balance of individual rights vs societal benefit
• Communicating results of the study

PARTICIPANT RIGHTS 2: ETHICAL GUIDELINES FOR EPIDEMIOLOGISTS^[3]

• Minimizing risk and protecting the welfare of research subjects
• Obtaining informed consent
• Ethical review of proposals
• Maintain public trust
• Meeting obligations to communities

PARTICIPANT RIGHTS 3: INDIVIDUAL vs. COMMUNITY RIGHTS

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

PARTICIPANT RIGHTS 4: PRIVACY AND CONFIDENTIALITY

• Data collected in an epidemiological study should not be released to any third party without the consent of the subject.
• Epidemiological 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 during all stages: collection, management, and analysis.
• Data ownership: who owns the data? The participant, the researcher, the institution?

PARTICIPANT RIGHTS 5: INCIDENTAL FINDINGS

• An epidemiologic study may uncover previously unrecognized diseases.
• 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 diseases.

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION-1: Misleading Role of The Media

• Media have a tendency to sensationalize issues that complicates later intelligent debates.
• Media may not understand the differences between published epidemiological findings and over-blow controversies.
• Risk reports that are not yet confirmed can be picked up by the media. It is difficult to keep epidemiological findings secret.
• Interpretation of RR, OR, and AR may not be true because of random errors (measured by the p-value), bias (systematic errors such as selection bias or information bias), and confounders. Fallacies of numerical reasoning.
• Biological vs statistical significance.

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION -  2: Examples of Controversies in Epidemiology

• Epidemiological controversies are best evaluated by a careful study of the underlying evidence and not be debated in the media.
• 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 et al. 1987 found that it was not.
• had been thought to be good for the heart but Willet and Vegetable-derived margarine Asherio 1994 found that it was bad for the heart.

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION -  2: Examples of Controversies in Epidemiology, con’t.

• 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 et al 1996 to cause cancer.
• Miller et 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).

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION - 3: Epidemiological Findings Affect/Effect Policy and Legal Rulings

• 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.

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION - 3: Epidemiological Findings Affect/Effect Policy and Legal Rulings con’t.

• Epidemiological evidence is concerned with populations whereas legal evidence pertains to individuals.
• Lung cancer patients sue tobacco companies for the causation of cancer. The judgment depends on establishing a causal relationship between tobacco and lung cancer. The counter-argument is that smoking is not the only cause of lung cancer.
• Criteria of causation: time sequence, the strength of the association, specificity of the association, biological plausibility, consistency, dose–effect relationship, and decrease of risk with the termination of exposure.

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION - 4 Ethnicity and Race ^[4]

• Race and ethnicity are used uniformly as confounding factors in most studies
• Race and ethnicity are not discrete but are continuous variables
• Racism in attributing disease risk to race with some races being better
• Race and genetics are artificial social-political constructs. Differences among races and ethnicities are minor/superficial and do not relate to disease risk. Analysis of the genome has destroyed the concept of race.
• Social and environmental factors underlie disease

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION - 5: Fallacies In Epidemiology ^[5]

• The fallacy of weight of evidence = a lot of weak evidence does not become strong evidence
• The fallacy of repeated citation = what is cited a lot need not be true
• The fallacy of authority based on individuals or books
• The fallacy of simple solution = parsimonious does not mean right
• The fallacy of risk = RR or OR may not be accurate for causality

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN STUDY INTERPRETATION and COMMUNICATION - 5: Fallacies In Epidemiology ^[5] con’t.

• The fallacy of inappropriate extrapolation, if too much or exposure is risky, is moderately safer?
• Fallacy of significance tests = p value not always true
• Fallacy of obsfuscation = use of complex language
• Fallacy of covert bias

 

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN CONFLICT OF INTEREST - 1^[6]

• Epidemiologists employed in academia can work relatively independently. Those working in government and industry are controlled by vested interests.
• Sponsors of research may force researchers to suppress some information.
• Conflict of interest.

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITY IN CONFLICT ON INTERESTS: 2: How The Tobacco Industry Interfered with Epidemiology^[7]

• Fostering controversy about the effects of passive smoking
• Paid consultants who write articles for academic journals
• Publishing biased review articles
• Research on non-tobacco causes of lung Cancer
• Hiding Results of Research on Tobacco

EPIDEMIOLOGISTS PROFESSIONAL RESPONSIBILITY IN CONFLICT OF INTEREST 3: Manipulation of Authorship

• Pressure to publish to win grants, promotions, and appointments. Many seek authorship they do not deserve.
• The International Committee of Medical Journal Editors criteria for authorship (2015) are^[8]:
• substantial contribution to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work
• drafting the work or revising it critically for important intellectual content
• final approval of the version to be published
• agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

EPIDEMIOLOGIST PROFESSIONAL RESPONSIBILITIES: CODE OF CONDUCT FOR EPIDEMIOLOGISTS^[9]

• Seek the truth in good faith without doing harm or jeopardizing personal integrity;
• Judge their own work and ideas and those of colleagues in an impartial manner;
• Disclose conflicts of interest to ethical review committees;
• Publicly acknowledge all research sponsorship;
• Publish all research with scientific merit;
• Refuse requests to withhold findings, change or tone down the content of reports, or delay publication unreasonably;
• Ensure sponsors agree in writing that results will be published regardless of the outcome and agree to the independence of the investigators;
• Declare sources of funding and possible conflicts of interests in publications.

REFERENCE:

1. https://cioms.ch/wp-content/uploads/2017/01/1991_INTERNATIONAL_GUIDELINES.pdf
2. David Selentano et al. Cordis Epidemiology 6th edition ElSevier Philadelphia 2019
3. Jones Bartlett. Epidemiology 101 2nd edition LEARNING Massachusetts 2018 by Robert H Friis p. 184
4. Raj Bhopal. Concepts of Epidemiology integrating the ideas, theories, principles, and methods of epidemiology, 3rd edition.  Oxford University Press. 2016. p. 408.
5. Raj Bhopal. Concepts of Epidemiology integrating the ideas, theories, principles, and methods of epidemiology, 3rd edition.  Oxford University Press. 2016, p. 414
6. David Selentano et al. Cordis Epidemiology 6th edition ElSevier Philadelphia 2019 page 402
7. Barnes and Bero 1998 quoted by in Concepts of Epidemiology integrating the ideas, theories, principles, and methods of epidemiology Raj Bhopal Oxford University Press 2016.  p. 405-406.
8. Raj Bhopal. Concepts of Epidemiology integrating the ideas, theories, principles, and methods of epidemiology, 3rd edition.  Oxford University Press. 2016, p. 40
9. Published by the International Epidemiology Association's European Group in 1998 updated in 2007

 

220905P - CROSS-SECTIONAL STUDIES 3: HEALTH SURVEYS

Presented at a Clinical Research Course for Pediatric Residency Program held at King Fahad Medical City, Riyadh on Thursday, 27 January 2022 (13:00 – 15:00 HRS). By Professor Omar Hasan Kasule Sr. MB ChB (MUK). MPH (Harvard), DrPH (Harvard) Professor of Epidemiology and Bioethics

DEFINITION OF HEALTH SURVEYS

• Surveys involve more subjects than the usual epidemiological sample.
• Surveys are used for the measurement of health and disease, assessment of needs, and assessment of service utilization and care.
• They may be population or sample surveys.
• Surveys may be cross-sectional or longitudinal.

PLANNING SURVEYS 1: PRELIMINARIES

• Literature survey,
• Stating objectives,
• Identifying and prioritizing the problem,
• Formulating a hypothesis.

PLANNING SURVEYS 2: SAMPLING

• Defining the population,
• Defining the sampling frame,
• Determining sample size and sampling method,
• The household is the usual sampling unit.
• Sampling may be simple random sampling, systematic sampling, stratified sampling, cluster sampling, or multistage sampling.

PLANNING SURVEYS 3: LOGISTICS

• Training study personnel,
• Considering logistics (approvals, manpower, materials, equipment., finance, transport, communication, and accommodation).

PLANNING SURVEYS 4: DATA COLLECTION

• Preparing and pre-testing the study questionnaire.
• Use existing data.
• Collect new data using a questionnaire (postal, telephone, diaries, and interview), physical examinations, direct observation, and laboratory investigations.
• The structure and contents of the survey report are determined by potential readers.
• The report is used to communicate information and also apply for funding.

220905P - CROSS-SECTIONAL STUDY

Presented at a Clinical Research Course for Pediatric Residency Program held at King Fahad Medical City, Riyadh on Thursday, 27 January 2022 (13:00 – 15:00 HRS). By Professor Omar Hasan Kasule Sr. MB ChB (MUK). MPH (Harvard), DrPH (Harvard) Professor of Epidemiology and Bioethics

LEARNING OBJECTIVES

• Cross-sectional studies: Definition and types (ecologic, prevalence, surveys).
• Cross-sectional studies: Design, analysis, and interpretation.
• Cross-sectional studies: Strengths and weaknesses.

KEYWORDS AND TERMS

• Cross-sectional study
• Ecological Study
• Naturalistic sampling
• Prevalence of the disease and of the risk factor
• Prevalence study

DEFINITION OF A CROSS-SECTIONAL STUDY

• The cross-sectional study is also called the prevalence study or naturalistic sampling.
• Its objective is the determination of the prevalence of risk factors and the prevalence of disease at a point in time (calendar time or an event like birth or death).
• Disease and exposure are ascertained simultaneously.

TYPES OF CROSS-SECTIONAL STUDIES

• A cross-sectional study can be descriptive or analytic or both.
• It may be done once or may be repeated.
• It may be that Individual-based studies collect information on individuals.
• It may be group-based (ecologic) studies collect aggregate information about groups of individuals.

USES OF CROSS-SECTIONAL STUDIES

• Community Diagnosis
• Preliminary study of disease etiology
• Assessment of health status
• Disease surveillance
• Public health planning
• Program evaluation.

ADVANTAGES OF CROSS-SECTIONAL STUDIES

• Simplicity,
• Rapid execution to provide rapid answers.

DISADVANTAGES OF CROSS-SECTIONAL STUDIES

• Inability to study etiology because the time sequence between exposure and outcome is unknown.
• Inability to study diseases with low prevalence.
• High respondent bias.
• Poor documentation of confounding factors.
• Over-representation of diseases of long duration.

DESIGN OF A CROSS-SECTIONAL STUDY: 2x2 TABLE

DATA COLLECTION FOR A CROSS-SECTIONAL STUDY

• The study may be based on the whole population or a sample.
• It may be based on individual sampling units or groups of individuals.
• The study sample is divided into 4 groups: a = exposed cases, b = unexposed cases, c = exposed noncases, and d = unexposed noncases.
• The total sample size is n = a + b + c + d; n is the only quantity fixed before data collection. The marginal totals are n₁ = a+b, n₀ = b+d, m₁ = a+b, and m₀ = c+d.
• None of the marginal totals is fixed.
• Cases are identified from clinical examinations, interviews, or clinical records.
• Data is collected by clinical examination, questionnaires, personal interviews, and review of clinical records.

STATISTICAL PARAMETERS

• The following descriptive statistics can be computed from a cross-sectional study: mean, standard deviation, median, percentile, quartiles, ratios, proportions, the prevalence of the risk factor, n₁/n, and the prevalence of the disease, m₁/n.
• The following analytic statistics can be computed: correlation coefficient, regression coefficient, odds ratio, and rate difference.
• The prevalence odds ratio is computed as POR = {p₁(1 - p₁)} / {p₀(1 - p₀)}.

  

220905P - CROSS-SECTIONAL STUDY 2: ECOLOGIC DESIGN

Presented at a Clinical Research Course for Pediatric Residency Program held at King Fahad Medical City, Riyadh on Thursday, 27 January 2022 (13:00 – 15:00 HRS). By Professor Omar Hasan Kasule Sr. MB ChB (MUK). MPH (Harvard), DrPH (Harvard) Professor of Epidemiology and Bioethics

KEYWORDS

• Survey report
• The survey, Field Survey
• The survey, Health Surveys
• The survey, Morbidity Survey
• The survey, Nutrition Survey

ECOLOGIC DESIGN

• Ecological studies, exploratory or analytic, study aggregate and not individual information.
• Groups commonly used are schools, factories, and countries.
• Exposure is measured as an overall group index.
• Outcome is measured as rates, proportions, and means.
• The correlation and regression coefficients are used as effect measures.

ADVANTAGES OF ECOLOGIC / CORRELATION STUDIES

• Low cost,
• Convenience,
• Easy analysis,
• Easy interpretation.

DISADVANTAGES OF ECOLOGIC STUDIES

• They generate but cannot test hypotheses.
• They cannot be used in definitive etiological research.
• They suffer from ecological fallacy (relation at the aggregate is not true at the individual level). They lack data to control for confounding.
• Data is often inaccurate or incomplete.
• Collinearity is a common problem.

 

220127P - FOLLOW-UP (COHORT) DESIGN

Presented at a Clinical Research Course for Pediatric Residency Program held at King Fahad Medical City, Riyadh on Thursday, 27 January 2022. By Professor Omar Hasan Kasule Sr. MB ChB (MUK). MPH (Harvard), DrPH (Harvard) Professor of Epidemiology and Bioethics

LEARNING OBJECTIVES

• Follow-up studies: Definition and types
• Follow-up studies: Design an analysis
• Follow-up studies: Strengths and weaknesses
• Determination of the sample size

KEYWORDS and TERMS

• Definition
• Cohort: study, closed cohort, open cohort
• Cumulative incidence
• Follow-up bias, study, ambispective, retrospective, prospective
• Loss to follow-up

DEFINITION

• A follow-up study (also called cohort study, incident study, prospective study, or longitudinal study), compares disease in exposed to disease in non-exposed groups after a period of follow-up.
• A follow-up study can be prospective (forward), retrospective (backward), or ambispective (both forward and backward) follow-up.
• In a nested case-control design, a case-control study is carried out within a larger follow-up study.
• The follow-up cohorts may be closed (fixed cohort) or open (dynamic cohort).
• Analysis of fixed cohorts is based on CI and that of open cohorts on IR.

STUDY DESIGN

• The study population is divided into the exposed and unexposed populations.
• A sample is taken from the exposed and another sample is taken from the unexposed.
• Both the exposed and unexposed samples are followed for the appearance of disease.
• The study may include matching, (one-to-one or one-to-many), pre and post-comparisons, multiple control groups, and stratification.

SOURCES of COHORTS

• Special exposure groups such as factory workers.
• Groups offering special resources such as health insurance subscribers.
• Institutionalized such as the army, and police.

SOURCES of EXPOSURE INFORMATION

• Existing records,
• Interviews/questionnaires,
• Medical examinations,
• Laboratory tests for biomarkers,
• Testing or evaluation of the environment.

OUTCOME ASSESSMENT

• The time of occurrence of the outcome must be defined precisely.
• The ascertainment of the outcome event must be standardized with clear criteria.
• Follow-up can be achieved by letter, telephone, surveillance of death certificates, and hospitals.
• Care must be taken to make sure that surveillance, follow-up, and ascertainment for the 2 groups are the same.

PROBLEMS of NON-RESPONSE in FOLLOW UP STUDIES

• In non-random non-response on exposure, the risk ratio is valid but the distribution of exposure in the community is not valid.
• In non-random non-response on outcome, the odds ratio is valid but the disease incidence rate is not valid.
• There is a more complex situation when there is non-response on both exposure and outcome.
• In general, random non-response is better than non-random or differential non-response.

PROBLEM of LOSS to FOLLOW UP

• Loss to follow-up can be related to the outcome, the exposure, and both outcome and exposure.
• The consequences of loss to follow-up are similar to those of non-response.
• In cases of regular follow-up, it is assumed that the loss occurred immediately after the last follow-up.
• If the loss to follow-up is related to an event such as death, it can be assumed that the loss was halfway between the last observation and the death.

FIVE TYPES of BIAS CAN ARISE in FOLLOW UP STUDIES

• Selection bias arises when the sample is not representative of the population.
• Follow-up bias arises when the loss to follow-up is unequal among the exposed and the unexposed, when disease occurrence leads to loss to follow-up, when people may move out of the study area because of the exposure being studied, and when the observation of the two groups is unequal.
• Information/misclassification bias arises due to measurement error or misdiagnosis.
• Confounding bias arises usually due to age and smoking because both are associated with many diseases.
• Post-hoc bias arises when cohort data is used to make observations that were not anticipated before.

STATISTICAL PARAMETERS

• Both incidence and risk statistics can be computed.
• The incidence statistics are the incidence rate and the cumulative incidence.
• The risk statistics are either the risk difference or the various ratio statistics (risk ratio, the rate ratio, the relative risk, or the odds ratio).

ADVANTAGES of the FOLLOW-UP DESIGN

• True risk ratio based on incidence rates,
• The time sequence is clear since exposure precedes disease,
• Incidence rates can be determined directly,
• Several outcomes of the same exposure can be studied simultaneously.

DISADVANTAGES of the FOLLOW-UP DESIGN

• Loss of subjects and interest due to long follow-up,
• Inability to compute the prevalence proportion of the risk factor,
• Use of large samples to ensure enough cases of the outcome,
• High cost: cost can be decreased by using existing monitoring/surveillance systems, historical cohorts, general population information instead of studying the unexposed population, and the nested case-control design.
• Follow-up studies are not suitable for the study of diseases with low incidence.

2 x2 TABLE

	Exposed	Unexposed	Total
Cases	a	b	m1
Noncases	c	d	m0
Person time	T1	T0	T

STATISTICAL COMPUTATIONS

• The incidence rate can be computed separately for each of the 2 groups.
• Incidence is defined as the number of cases of a disease divided by the total person-time of follow-up thus IR = n/PT.
• If the period of follow-up is long, IR can be computed for several time intervals, thus the interval incidence is defined as IR_j = n_j / PT_j.
• The MH chi-square is computed as [a – mT₁/T] / [mT₁ T₀ / (T₀)²].
• The incidence rate difference IRD is computed as a/T₁ – b/ T₀ with 95% confidence intervals of IRD +/- 1.96 {(IRD)²/c²}^1/2 = IRD (1 +/- 1.96/c).
• The incidence rate ratio, IRR, is computed as (a/T₁) / (b/T₀) with 95% confidence intervals computed as (IRR) ^{1+/- 1.96/c}.

HISTORICAL PROSPECTIVE FOLLOW UP^[1]

• In 1951, the British Medical Association forwarded to all British doctors a questionnaire about their smoking habits, and 34440 men replied. With few exceptions, all men who replied in 1951 have been followed for 20 years.
• The certified causes of all 10 072 deaths and subsequent changes in smoking habits were recorded.
• The ratio of the death rate among cigarette smokers to that among lifelong non-smokers of comparable age was, for men under 70 years, about 2:1, while for men over 70 years, it was about 1-5:1.
• These ratios suggest that between a half and a third of all cigarette smokers will die because of their smoking if the excess death rates are actually caused by smoking.
• To investigate whether this is the case, the relation of many different causes of death to age and tobacco consumption was examined, as were the effects of giving up smoking. Smoking caused death chiefly by heart disease among middle-aged men (and, with less extreme relative risk, among old men,) lung cancer, chronic obstructive lung disease, and various vascular diseases.
• The distinctive features of this study were the completeness of follow-up, the accuracy of death certification, and the fact that the study population as a whole reduced its cigarette consumption substantially during the period of observation. As a result, lung cancer grew relatively less common as the study progressed, but other cancers did not, thus illustrating in an unusual way the causal nature of the association between smoking and lung cancer.

HISTORICAL PROSPECTIVE FOLLOW UP^[2]

• In order to investigate the nature of the association between involuntarily delayed first birth and risk of breast cancer, 1083 white women who had been evaluated and treated for infertility from 1945-1965 were followed prospectively through April 1978 to ascertain their breast cancer incidence.
• These women were categorized as to the cause of infertility into two groups, those with endogenous progesterone deficiency (PD) and those with nonhormonal causes (NH).
• Women in the PD group had 5.4 times the risk of premenopausal breast cancer compared to women in the NH group.
• This excess risk could not be explained by differences between the two groups in ages at menarche or menopause, history of oral contraceptive use, history of benign breast disease, or age at first birth.
• Women in the PD group also experienced a 10-fold increase in deaths from all malignant neoplasms compared to the NH group.
• The incidence of postmenopausal breast cancer did not differ significantly between the two groups.

CONTEMPORARY PROSPECTIVE FOLLOW UP^[3]

• Postprandial hypotension (PPH) is common among the elderly. However, it is unknown whether the presence of PPH can predict the development of new cardiovascular disease (CVD) in the elderly during the long-term period.
• This study aimed to prospectively evaluate the presence of PPH and the development of new CVD within a 36-month period in 94 community-dwelling elderly people without a history of CVD.
• PPH was diagnosed in 47 (50.0%) participants at baseline and in 7 (7.4%) during the follow-up period. Thirty participants (31.9%) developed new CVD within 36 months.
• The multivariate analysis indicated that the relationship between PPH and the development of new CVD remained even after controlling for other variables as covariates.
• In conclusion, the presence of PPH can predict the development of new CVD. Elderly people with PPH may require close surveillance to prevent CVD.

CONTEMPORARY RETROSPECTIVE FOLLOW UP^[4]

• The aim of this study was to quantify the risk of hair loss with different antidepressants. A retrospective cohort study design using a large health claims database in the USA from 2006 to 2014 was utilized.
• A cohort of new users and mutually exclusive users of fluoxetine, fluvoxamine, sertraline, citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion were followed to the first diagnosis of alopecia.
• The cohort was comprised of 1 25 40 new users of fluoxetine, fluvoxamine, sertraline, citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion, with sertraline the most commonly prescribed (N=190 27) and fluvoxamine (N=3010) the least prescribed.
• Compared with bupropion, all other antidepressants had a lower risk of hair loss.
• The results of this large population-based cohort study suggest an increase in the risk of hair loss with bupropion compared with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, whereas paroxetine had the lowest risk.

COMPARISON of RETROSPECTIVE vs PROSPECTIVE FOLLOW UP

• Retrospective is based on information in old stored records or analysis of biological samples.
• Prospective is based on new information generated during the study period.
• The quality of data in retrospect is difficult to ascertain because the researcher was not there.
• Quality of data in prospective can be controlled and ascertained.
• Confounders are more difficult to identify and control in retrospective follow-up.

COMPARISON of FOLLOW-UP and CASE-CONTROL STUDIES

	FOLLOW-UP STUDY	CASE-CONTROL STUDY
Source of data	New data collection	Uses existing data + additional information as needed
Sample size	Big numbers	Small numbers
Observer bias	Knowledge of exposure Affects the report or search for a diagnosis	Knowledge of disease affects interview or report of exposure
Respondent bias	Unlikely: response on exposure given before illness	Likely: response on exposure given after illness leads to recall bias
Risk Estimates & comparisons	Pr(D+/E+) vs Pr(D+/E-)	Pr(E+/D+) vs Pr(E+/D-)
Study duration	Usually long (more than 1 year)	Usually brief
Disease incidence	Best for diseases with High incidence	Good for both low and high-incidence diseases
Cost of study	Expensive	Cheap
Sampling	Probability sample easy to select	A probability sample of controls is difficult to select; so they are like cases except for disease
Study starting point	Exposure initiation	Disease diagnosis
Sample size determinant	Disease frequencies	Exposure frequencies

COMPARISON of FOLLOW-UP and EXPERIMENTAL STUDIES

	FOLLOW-UP STUDY	EXPERIMENTAL
Source of data	New data collection	New data collection
Observer bias	Knowledge of exposure Affects the report of diagnosis	Knowledge of allocation group affects the assessment of the outcome
Respondent bias	Unlikely: response on exposure given before illness	Unlikely; the outcome is assessed and not asked about
Risk Estimates & comparisons	Pr(D+/E+) vs Pr(D+/E-)	Pr(D+/E+) vs Pr(D+/E-)
Study duration	Usually long (more than 1 year)	Usually long more than 1 year
Disease incidence	Best for diseases with High incidence	Best for situations with a high occurrence of the outcome
Cost of study	Expensive	Expensive
Sampling	Probability sample easy to select	Randomization and not probability samples used
Study starting point	Exposure initiation	Point of randomization
Ethical issues	Fewer	Many
Sample size determinant	Disease frequencies	Outcome frequency

 

REFERENCES:

1. Doll R, Peto R. Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J. 1976 Dec 25;2(6051):1525-36.
2. Cowan LD, Gordis L, Tonascia JA, Jones GS. Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol. 1981 Aug;114(2):209-17.
3. Jang A. Postprandial Hypotension as a Risk Factor for the Development of New Cardiovascular Disease: A Prospective Cohort Study with 36 Month Follow-Up in Community-Dwelling Elderly People. J Clin Med. 2020 Jan 27;9(2).
4. Etminan M1, Sodhi M2, Procyshyn RM3, Guo M1, Carleton BC. Risk of hair loss with different antidepressants: a comparative retrospective cohort study. Int Clin Psychopharmacol. 2018 Jan;33(1):44-48