Institutional Review Board (IRB) and Clinical Research

1. Institutional Review Board (IRB) and Clinical Research Shu B. Chan, MD, MS, FACEP Research Director, Emergency Medicine Residency Program, Member, IRB Resurrection Medical Center

2. Agenda • History of the development of the IRB • Composition of the IRB • Operation of the IRB • Duties of the IRB • IRB and the EM Resident • Types of IRB Approvals • Helpful Tips Regarding IRB Submissions

3. Nuremberg Code-1949 • Along with the trials of war criminals before the Nuremberg Military Tribunals were a series of directives regarding human experimentation • Voluntary consent of the human subject is absolutely essential • Experiments should be necessary for the good of society and likely to yield results

4. Nuremberg Code • Experiment designed, based, and justified on prior knowledge • Avoid all unnecessary physical and mental suffering and injury • No a priori reason to believe that death or disability will occur • Risk should not exceed the benefits • Proper preparation to protect the subjects from possibilities of harm

5. Nuremberg Code • Experiments done by qualified persons • Right of the subject to terminate the experiment • Duty of the scientist in charge to terminate an experiment if continuation is likely to result in injury, disability, or death

6. Declaration of Helsinki-1964 • The World Medical Association adopted a set of ethical principles for medical research involving human subjects • These principles included all the directives from Nuremberg and expanded on them • Medical research involving human subjects includes research on identifiable human material or identifiable data

7. Declaration of Helsinki-1964 • When providing care, the physician shall act only in the patient’s interest • Some research populations are vulnerable and require special protection • Clear formation of an experimental protocol • An “ethical review” committee, independent of the researcher should review all protocols • Confidentiality and privacy of the subject must be respected

8. The Belmont Report-1979 • Report of the meeting of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research at the Belmont Conference Center at the Smithsonian • By this time IRB have been established in most institutions and having difficulties implementing all the rules and directives from Nuremberg and Helsinki

9. The Belmont Report-1979 • It was felt that to better guide the researchers and IRB reviewers, especially in more complex situations, boarder general ethical principles were needed • The concept was that these boarder principles would provide the basis for interpretation of the specific rules and guidelines

10. The Three Basic Ethical Principles from the Belmont Report • Principle One: Respect of Persons (a.k.a. Autonomy) • The principle of “respect for persons” is divided into two moral requirements • First is to acknowledge that to respect a person’s autonomy requires that the person enters into the research on a voluntary basis and has adequate information to make such a decision • Second is to recognize that certain individuals may have decreased capacity for self-determination and so require special protection

11. The Three Basic Ethical Principles from the Belmont Report • Principle Two: Beneficence • The principle of “beneficence” can be summarized by two general rules • “Do no harm” - the old Hippocratic maxim • However, many times this dictum does not lend itself to clear cut interpretations and so the second general rule is more applicable • “Maximize possible benefits and minimize possible harms”

12. The Three Basic Ethical Principles from the Belmont Report • Principle Three: Justice • The principle of “justice” can be understood by considering these important questions • Who should receive the benefits of the research? • Who will receive the benefits of the research? • Who will bear the burdens of the research? • There needs to be fairness in distribution of persons involved with the answers to those questions

13. Composition of the IRB • Since much clinical research is funded or under the perusal of the federal government, the Department of Health and Human Services ( Office for Protection from Research Risks) has set specific rules regarding the composition and duties of individual local IRB

14. Composition of the IRB • Minimum of five members • Diversity of race, gender, and cultural background • Diversity of experience and expertise • Professional competence necessary to review research • Members may not review their own projects

15. Operations of the IRB • Have written procedures and follow them • Majority of members must be present to convene a meeting • Approval of a research project requires the approval of a majority of those members present at the meeting • Officials of the institution may not approve research that has not been IRB approved

16. Duties of the IRB • Review and have authority to approve, require modifications, or disapprove all research activities involving humans • Review and approve informed consent from the research subjects • Continuing review of approved research not less than once per year

17. Duties of the IRB • Review and approval in accordance with the three Belmont principles of • 1: Autonomy (Respect of Person) • 2: Beneficence • 3: Justice • Prepare and maintain adequate records and documentation of IRB activities

18. Duties of the IRB • In addition, the IRB must follow more specific rules when reviewing research involving • Pregnant women • Fetuses • Children • Prisoners

19. IRB and the EM Resident • Almost all research done by an EM resident will involve humans in some fashion • The humans need not be “experimental subjects” for the research to fall under IRB perusal • Recall that the Helsinki directives expanded research protection to all identifiable human data

20. IRB and the EM Resident • The IRB process may be time consuming and residents have specific time tables • Protocol modifications requested by an IRB may make a project not doable • The IRB has the authority to halt a project at any point

21. Types of IRB Approvals • Expedited review and approval • The chairperson may individually review and approve a proposal or designate an IRB member(s) to review and approve a proposal • There are strict guidelines on when an expedited review is allowed • However a proposal can only be disapproved by the full IRB

22. Types of IRB Approvals • Exemption from further review • This is not an exemption from review • All research involving human must have some sort of initial review and approval • The exemption is so that future review by the IRB is not needed, thus not having to submit follow up reports

23. Types of IRB Approvals • Waiver of written informed consent • Key to the first Belmont principle of autonomy is the requirement that all human subjects give informed consent to the study • The IRB may give a waiver so that this informed consent need not be in written form • If a written consent form is not included in an application, then that application is incomplete unless a waiver has not requested

24. Tips for IRB Submission • Because IRB operate under very specific rules and guidelines from the federal government, record keeping tend to be very strict • Make sure the application is complete • Leave no blanks, write not-applicable if so • Be sure consent templates and other attachments are in order and included

25. Tips for IRB Submission • All submitted applications should be signed • All investigators in the study should be listed • Be sure to submit the necessary number of copies • Don’t forget to include any funding source, even when the amount is minuscule or the funding is not cash • Have a clear and concise cover letter

26. Tips for IRB Submission • Many studies by residents are retrospective and involve no or minimal risk to the subjects and so qualifies for expedited review • If the study involves no or minimal risk, then very often further IRB oversight is unnecessary and the study can be exempt

27. Tips for IRB Submission • If the study qualifies for expedited or exempt status, so state that in the application or cover letter and specifically ask for expedited and/or exempt status • Be sure to list the reasons for the request for expedited and/or exempt status • Minimal risks • Retrospective study design, etc.

28. Tips for IRB Submission • If a waiver of written informed consent is requested • Be sure that the section of the application where the written consent is placed has a notation that a waiver is requested • Regardless of whether a waiver is requested or not, the process of obtaining informed consent still must be clearly spelled out

29. Tips for IRB Submission • Loss of subject confidentiality is an important aspect embodied in the first Belmont principle of autonomy • This issue has become a hot one since the passage of HIPAA regulations • Be very detailed when describing how subject confidentiality is maintained

30. Tips for IRB Submission • The IRB is charged with protecting the economic rights of the subjects also under the Belmont principle of justice • Any possible increased expense to the subjects must be clearly explained and justified • Provisions for meeting these expenses must be stated

31. Tips for IRB Submission • If using an established template for IRB application, be sure to review the documents completely so that the application is specific to your project • When in doubt, give more not less information • Have the application reviewed by an experienced mentor