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Presentation at a “Clinical Research Course” held at King Fahad Medical City, Riyadh on 19 August 2020 by Professor Omar Hasan Kasule Sr. MB ChB (MUK). MPH (Harvard), DrPH (Harvard). Chairman of the Institutional Review Board, King Fahad Medical City
FUNCTIONS OF IRB:
• Initial evaluation and approval of research proposals to make sure they fulfill the requirements of the Saudi regulations on human research and the international consensus Good Clinical Practice Guidelines. Above these regulations, IRB must ensure the highest ethical standards in any research.
• Follow-up evaluation and approval of matters arising in the course of the research: protocol amendments, study termination / completion.
• Monitoring of study execution by checking on vital issues such as proper consenting procedures, the confidentiality of the data, and complete and up-to-date documentation, completeness and quality of AE reporting1, and any ethical violations / protocol deviations.
MEMBERSHIP OF IRB - 1:
• Membership of the IRB must have a diversity of medical professional competencies (clinical and non-clinical) to make sure that for every project reviewed there is a member from the relevant discipline and not necessarily the sub-discipline. Physicians tend to dominate IRBs.
• Membership should comprise representatives of the major medical and surgical specializations practiced in the hospital or region, hospital physicians, hospital nursing staff, general practitioners, pharmacists, statisticians, ethicists, and laypersons from the community.
• At least one of the members must be a normal community representative with no affiliation to the institution. This member should not have any connection with medical work.
MEMBERSHIP OF IRB - 2:
• In selecting members attempts should be made to make sure that all genders and age groups are well represented.
• Members should be selected on their own personal merit as people with knowledge, skills, and sound judgment. They should discuss the proposals as individuals and not representatives of people with knowledge, skills, and sound judgment. They should discuss the proposals as individuals and not representatives of any department, unit, organization, or profession.
• Members are appointed by the hospital, the health authority in the region, or the government.
• The period of service on the committee is usually three years. Membership may be renewed. Staggered renewal of membership. A member should serve 2-3 terms.
SCOPE OF RESEARCH REVIEW BY IRB:
• The committee assesses research proposals and protocols that have ethical implications: (a) research on patients, volunteers, the recently dead, fetal, or embryological tissues (b) research with the potential to breach confidentiality.
• All research however must be submitted to the IRB Chairman because the researcher cannot be trusted to determine the classification.
• The Chairman will determine which proposals are exempt (no risk no ethical issues) and which are expedited (minimal risk) and approve them immediately.
• The chairman will determine and approve expedited proposals (minimal patient risk) and if need be can consult one or more members of the committee.
• Full review is done for research with human intervention.
DOCUMENTS SUBMITTED FOR IRB REVIEW:
• Exempt proposals submitted on a special form with the proposal attached. The form must be signed by the PI and HOD.
• Full and expedited: Protocols, investigator brochures, and consent documents of proposals with potentially significant patient risk are sent to all IRB members at least 2 weeks in advance for review with those from the relevant disciplines being asked to make a more detailed analysis and make a presentation to the IRB.
• The CVs of investigators and certification of GCP must be attached.
IRB MEETING
• The committee must be provided with adequate secretarial and logistic assistance to carry out its functions well.
• A quorum of at least half of the members will be necessary for holding a meeting. Members who cannot attend can send written comments and may/may not vote.
• The committee meets in private to preserve confidentiality. Others argue that they should meet in public for more transparency.3
• If the issues are complicated the investigator may be invited to the meeting to explain.
• Any member of the committee involved in a project will recuse himself when that project comes up for discussion.
CRITERIA OF IRB APPROVAL - 1
• The two main considerations in IRB decisions are: informed consent and patient safety.
• Informed and voluntary consent following full disclosure of objectives, risks and benefits of the research, the right to abstain or withdraw from the study. Special scrutiny of proxy consent for the vulnerable will be made to ensure there is no abuse4,5,6. The investigator must submit reasons in writing in cases in which full disclosure is deemed inappropriate.
• Patient safety based on a careful weighing of benefits and risks.
• Confidentiality (use of certificates of confidentiality7) and security of the data.
CRITERIA OF IRB APPROVAL - 2
• Scientific merit: objectives clearly states and attainable, research design and statistical methods are adequate to produce clinically and scientifically useful results. Outside experts may be consulted. The committee will compare the scientific merit and benefit of the research against risks and costs to patients. Decision-making procedures may improve the risk-benefit discourse8.
• Qualification of the researchers based on study of their detailed resumes.
• Adequacy of research facilities
• No conflicts of interest
DECISIONS OF IRB
• IRB decisions are best taken by consensus but if this is not possible the decision will be based on a simple majority of the members attending if the quorum is assured. Minority views should be recorded.
• The decision of the committee may be full approval, conditional approval, deferment, or rejection. Reasons should be provided for projects approved conditionally or those that are rejected. If the investigator fulfills the missing information the chairman may approve a conditional approval without returning to the full committee.
FOLLOW-UP OF RESEARCH
• The committee must monitor the progress of the research project and must receive reports of all adverse reactions whether related to the drug tested or not. AE reports from all sites of multi-center trials must be submitted.
• Members of the committee can make on-site inspections to make sure that the approved protocol is adhered to and to inspect research documents and records.
• Regular monitoring meetings are held to review the following: progress of recruitment of research subjects, changes to the protocol, adverse reactions, the process of informed consent, refusals and withdrawals, and case record forms.
• Warning letters.9
OVERSIGHT OF IRB
• The committee keeps full records of all its actions. Records are not privileged if a suit arises.
• It submits an annual report listing all proposals considered in the past year, the number approved, and any matters that deserve attention from higher authorities.
• The Chairman of IRB reports to the highest official in the institution.
• Tool for IRB self-assessment10.
• Researchers have a right of appeal.
PROBLEMS OF IRB 1: HUMAN AND MATERIAL RESOURCES
• Not enough resources (financial, secretarial, office space) for their work.
• Chairman has a lot of administrative duties because of fulfilling research regulations and legal documents needed by international sponsors.
• Work of IRBs moving from ethics to research governance11.
• IRBs struggle to catch up with new clinical research regulations12.
PROBLEMS OF IRB 3: MEMBERS
• Members’ training needs often not fulfilled: lack of time & changing regulations. A specific curriculum is needed covering: committee working; scientific method; ethical analysis and the regulatory framework13.
• Community member participation is limited14. Confusion about the roles of nonaffiliated and non-scientific members15. Varying ways of using community members16.
• Conflicts of interest within IRB17: the obvious and the non-obvious.
IRB PROBLEMS: SUBMISSIONS - 1
• Poorly designed and written research proposals. Many procedural errors;18 IRB normally gives researchers advice on improving their proposals instead of rejecting them outright.
• Sponsored research is over-documented and the sponsors expect IRB to review and approve many documents that have no direct relation to research ethics.
IRB PROBLEMS: SUBMISSIONS - 2
• What projects to review: Determination of minimal risk is not easy for example is trauma and sex survey minimal risk?19 Is Medical education research under IRB review?20,21 Are quality improvement projects research?22 Chart reviews, case reports, observational studies part of IRB?23 IRBs have problems dealing with community-based research.24
• Retrospective approvals to enable publications.
• Problem of dealing with incidental findings.25
IRB PROBLEMS: GUIDELINES - 1
• Inconsistencies among IRBs26 and difficulty of setting standards27. No homogenous code, improper application of standards, lack of auditing capabilities28.
• Different IRBs emphasize different criteria29. IRBs do not uniformly follow the common rule30. Common guidelines reduce the variability31.
IRB PROBLEMS: GUIDELINES - 2
• Varying decisions of IRBs for multicenter proposals32,33,34,35,36,37. Centralized IRBs have been suggested to standardize but they also have their problems38,39. Cost-benefit considerations40. Centralized IRBs are remote from researchers and the site of research? Wring decisions.
• Should IRBs follow centralized guidelines or should add their own local ones?41 Should IRBs consider community values?42
IRB PROBLEMS: DIFFICULT DECISIONS - 1
• Problems in making decisions on re-use without informed consent that involves stored tissue43 for the same research or different research.
• Deciding on research genetic research (confidentiality and sending material overseas. Researcher and IRB Chair perspectives on genomic research were different44.
IRB PROBLEMS: DIFFICULT DECISIONS - 2
• Hot protocols: facial transplants require different approaches45.
• Issues of consent: Online survey tools may not fulfill consent rules46. Waiver of consent for emergency research47, long consent forms / Arabic translations.
• Is IRB a rubberstamp function: Most research projects submitted are approved48. The majority of IRBs are satisfied with submissions by sponsors49.
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