220907P - ISSUES IN RESEARCH ETHICS

Presentation at a PICU Fellowship Research Program held at PICU Conference Room Floor 1 Children Hospital, King Fahad Medical City, Riyadh on 06 September 2022. By Dr. Omar Hasan Kasule Sr MB ChB (MUK), MPH (Harvard) DrPH (Harvard) Professor of Epidemiology and Bioethics, King Fahad Medical City

 

1. BACKGROUND INFORMATION ABOUT THE RESEARCH

• Therapeutic Research
• Clinical Trials on Humans: Phase 1,2,3,4
• Non-Therapeutic Experiments
• Community-Based Experimentation

 

2. THE NUREMBER CODE 1946:

• Voluntary Informed Consent
• No Random or Unnecessary Experiments
• Animal Experiments first
• Knowledge Of Disease Natural History
• Avoiding Unnecessary Physical and Mental Suffering
• The Researchers Must Be Scientifically Qualified
• Subjects Can Withdraw at Any Time
• The Investigation is Stopped if the Patient is in Danger.

 

3. HELSINKI DECLARATION 1962, 1996:

• Generally Accepted Scientific Principles
• Risk-Benefit Assessment.
• Subject Integrity and Welfare
• Full Disclosure

 

4. GOOD CLINICAL PRACTICE GUIDELINES

• Follow the ethical principles of the Helsinki Declaration
• Benefits justify risks
• Rights of patient > Rights and interests of society
• Prior clinical and non-clinical information
• Follow protocol
• Qualified physicians
• Free informed consent
• Confidentiality
• Good manufacturing practice
• Quality control

 

5. SECTIONS OF THE GCP MANUAL

• The Institutional Review Board:
• The investigator
• The sponsor
• Clinical trial protocol:
• Investigator brochure

 

6. MAJOR ETHICAL ISSUES IN RESEARCH-1:

• Informed consent/autonomy
• Frequently violated
• Autonomous right to protect life, hafidh al nafs
• Self interest in consent
• Competence to consent
• The benefit-risk ratio
• The principle of injury, qa’idat al dharar
• Research policy aims at minimizing risk to the research subject
• Report and management of adverse events

 

7. INFORMED CONSENT CHECKLIST (Required Elements)

• Participating, supporting, or organizing institutions and those who may benefit from the project’s results listed?
• A statement that the study involves research.
• An explanation of the purposes of the research.
• The expected duration of the participant’s participation.
• A description of the procedures to be followed.
• Identification of any procedures which are experimental (vs. standard care).
• A description of any reasonably foreseeable risks or discomforts to the participant.
• A description of any benefits to the participant or to others that may reasonably be expected from the research.
• A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the participant.

 

8. INFORMED CONSENT CHECKLIST (Required Elements) con’t - 1

• A statement describing the extent, if any, to which confidentiality of records identifying the participant will be maintained
• If the research is subject to SFDA regulation, a statement that notes the possibility that SFDA may inspect the records.
• For research involving more than minimal risk, an explanation as to whether any compensation is available if injury occurs.
• An explanation as to whether any medical treatments are available if injury occurs.
• If so, what they consist of, or where further information may be obtained.
• An explanation of whom to contact for answers to pertinent questions about the research and research participants' rights.
• Who to contact in the event of a research-related injury to the participant?
• A statement that participation is voluntary.
• A statement that refusal to participate will involve no penalty or loss of benefits to which the participant is otherwise entitled.

 

9. INFORMED CONSENT CHECKLIST (Required Elements) con’t - 2

• A statement that the particular treatment or procedure may involve risks to the participant which are currently unforeseeable.
• The subject’s responsibilities.
• Any additional costs to the participant that may result from participation in the research.
• The anticipated prorated payment, if any, to the subject for participating in the trial.
• A statement that significant new findings developed during the course of the research which may relate to the participant’s willingness to continue participation will be provided to the participant.
• Anticipated circumstances under which the participant’s participation may be terminated by the investigator without regard to the participant’s consent.
• The approximate number of participants involved in the study (at this site and all sites).

 

10. ADVERSE EVENTS AND PROTOCOL DEVIATIONS/VIOLATIONS DATIX REPORTING

 

11. DISCUSSION CASES ON CONFLICT   OF   INTERESTS

The pharmaceutical company wanted to conduct a 4th phase study of its new unpopular headache medication and offered SAR500 to physicians in private practice and SAR20 to physicians in public hospitals for every patient recruited into the study. All the physician had to do was to prescribe the drug and complete a short 5-item questionnaire. A company representative would pick up the data sheets at the end of every day’s work.

12. DISCUSSION CASES ON PAYMENT TO RESEARCH SUBJECTS

Researchers advertised for male obese youths aged 18-25 years to join a randomized study that compared dietary control to surgical control of obesity. The surgery used was innovative including laparotomy and surgical dissection of lipid tissue from the abdominal cavity. Subjects undergoing surgery were each paid USD2000 before the operation and USD8000 after 6 months of follow-up.

13. DISCUSSION CASES ON THE PROCESSES OF INFORMED CONSENT - 1

A randomized study was carried out among pregnant women to study the impact of iron supplementation on pre-delivery hemoglobin levels. Informed consent was obtained after full disclosure of all facts. A questionnaire at the end of the study surprised researchers because the women could not remember that any research was carried out; they knew it was all routine medical care.

14. DISCUSSION CASES ON THE PROCESSES OF INFORMED CONSENT - 2

Patients in a randomized cancer drug trial had to read a 5-page Arabic translation of the disclosure statement and then sign the consent; 2/10 signed without reading but listened to a 2-minute explanation by the principal researcher. 18/20 decided to take it home for study and brought it back fully signed and dated.

15. DISCUSSION CASES ON THE PROCESSES OF INFORMED CONSENT - 3

A terminal cancer patient refused participation in a randomized trial of a new chemotherapeutic agent claiming that he had a right to refuse and that the research was not in his interests and will not contribute to his welfare. The principal investigator was called to convince the patient. He told him that participation was a duty of each citizen and that it was immoral to shirk that duty. He said ‘If everybody refused to participate how can we develop new drugs?’. The patient reluctantly signed the informed consent form.

16. DISCUSSION CASES ON RESEARCH WITHOUT CONSENT - 1

Researchers wanted to study the effect of restricting teenagers’ pocket money on their cigarette addiction. Parents were randomized to various amounts of pocket money for teenagers every day. Observers acting as spies hung out with the teenagers and reported on their smoking behaviors. IRB was asked to approve the study without disclosure of its objectives and procedures to the teenagers because that would invalidate the results.

17. DISCUSSION CASES ON JUSTICE

The consultant warned his resident to make sure women of childbearing age are systematically excluded from a randomized study of a new drug whose teratogenic properties were unknown.

18. DISCUSSION CASES ON PUBLICATION BIAS - 1

A researcher studying two treatments compared outcomes on discharge from the hospital. The outcome results of 10 out of 90 patients were lost due to a computer error and there was no paper backup because all the research was computerized. The patients could also not be traced. The researcher decided on a worst-case scenario and assigned all the 10 to the worst outcome and analyzed the results. Fearing confusing the reviewers and readers, he did not mention the assignment or the outcome.

19. DISCUSSION CASES ON PUBLICATION BIAS - 2

The editorial board of the faculty journal had an unwritten understanding shared by all members that negative clinical trials would not be published because they would have no new information for the readers. The message trickled through and researchers stopped submitting such trials for publication. As a result, the journal became famous for being the source of breakthrough research on new therapies.

20. DISCUSSION CASES ON PUBLICATION BIAS - 3

The head of the department a senior professor of surgery asked his residents to undertake research comparing two surgical techniques. He gave them detailed guidelines on the literature survey, study design, and study execution. He never took part in the actual research or the writing of the paper but gave advice on a daily basis whenever they asked him. When the manuscript was ready for publication, he asked that his name be put as the first author. The residents wanted him to be the last author.

21. OTHER DISCUSSION CASES

Residents submitted a proposal promptly rejected by IRB for lack of proper consent procedures and the inexperience of the investigators. They resubmitted it with a senior consultant as principal investigator, changed the wording of the title, and changed nothing else. The proposal was accepted.