The Institutional Review Board (IRB) and its functions

1. The Institutional Review Board (IRB) and its functions Anthony K. Wutoh, Ph.D., R.Ph. Professor School of Pharmacy College of Pharmacy, Nursing and Allied Health Sciences Co-Chairman, Institutional Review Board

2. Howard University IRB

3. What is your image of the IRB?

4. Why were/are IRBs needed? • Tuskegee Syphilis Study (Alabama, 1932-1972) • Nazi Experiments (1930s-1940s) • Stanley Milgram's experiment ."Obedience and Individual Responsibility" (Yale, 1961-1963) • Willowbrook Study (New York, 1963-1966) • Tearoom sex (Washington Univ., 1960s) • Research conducted in prisoners, children and other vulnerable populations

6. Recent Violations • In a totally unprecedented flurry of enforcement activity, the National Institutes of Health (NIH) Office for Protection from Research Risks (OPRR) stopped research at Rush-Presbyterian-St. Luke's Medical Center (AP 1998), the West Los Angeles Veterans Affairs Medical Center (Monmaney 1999; Hilts 1999a), Duke University (Stout 1999; Weiss 1999), the University of Illinois at Chicago (Guerrero and Herguth 1999; Grahnke and Ritter 1999), the University of Colorado (Hubler 1999), Virginia Commonwealth University (Mathews 2000), and most recently, the University of Alabama at Birmingham (Hansen and Spencer 2000; Hilts 2000). • While there have been some substantive concerns relating to subject enrollment and informed consent, most of these sanctions have been levied because of sloppy and inadequate operation of institutional review boards (IRBs) and slow or inadequate response to OPRR's concerns.

7. Violations • Researchers at Stanford University were permitted by the state in 1997 to test the use of Depakote in incarcerated adolescent males to see if the drug would reduce aggressive behavior (Weber 1999). • Researchers at the New York State Psychiatric Institute, the Mount Sinai School of Medicine, and the Research Foundation of the City University of New York came under fire for giving fenfluramine to young children, many of whom were Hispanic or African American. The children were at-risk younger siblings of child offenders identified by the researchers through court records (Hilts 1998a; Waldman 1999; Bernstein 1999). • In the early 1990s, plastic surgeons at the Manhattan Eye, Ear, and Throat Hospital performed a study in which different surgical face-lift techniques were used on the opposite sides of patients' faces without securing IRB approval and without express patient consent (Hilts 1998b).

8. Jesse Gelsinger and Gene Therapy (U. of Penn.) • In 1999-2000 the Food and Drug Administration stopped all gene therapy trials at the University of Pennsylvania, because of alleged shortcomings and violations of protocols, revealed in an audit .prompted by the death of Jesse Gelsinger • Gelsinger suffered from Ornithine transcarbamylase (OTC) deficiency, a rare metabolic disorder. • Gelsinger's death also prompted a revelation of at least six deaths in other gene therapy trials that had not been reported to the NIH, in violation of the law, because the investigators determined the deaths were caused by the subjects' disease and not the experimental therapy. • Several institutions and foundations sponsoring genetic therapy research halted trials because of concerns about patient safety. The public hearings also spurred the reporting to NIH of 652 adverse events in trials using modified adenoviruses (as used in the Penn trial), compared to only 39 that had been reported promptly as required by law. • Issues - Conflict of interest, did not meet the inclusion criteria, consent forms did not adequately discuss risks.

9. Research Regulations • In 1979, the federal government developed regulations of ethical principals underlying the current regulations and standards that are contained in the Belmont Report. • It was the capstone of the National Commission for the Protection of Human participants of Biomedical and Behavioral Research. It outlines the ethical principals upon which the ethics of a research study are evaluated in the United States. • The Belmont Report embodies the moral consensus upon which stand our present US Federal regulations governing the ethics of human participants research conduct with Federal funds from the majority of Federal agencies. • Our present regulations formulize The Belmont Report's requirements for informed consent and establish another Commission recommendation that formalized and extended the existing peer review system of that time, which has matured into the Institutional Review Board (IRB) system that we have today.

10. Historical Overview • The protection of the rights and privacy of human participants involved in research activities is mandated by federal law.  • The National Research Act Public Law 99-158, The Health Research Extension Act of 1985, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research provide guidelines for research with human participants to ensure their protection in the design and conduct of research. • These federal regulations require that any institution requesting and receiving funds from a federal department or agency for research involving human participants must assure that such research is reviewed and approved by the institution's institutional review board (IRB). 

11. IRB Review Process

12. Purpose of the IRB at Howard University • Review research proposals, projects, and activities that involve human participants; • Determine for each activity or proposed activity if human participants will be placed at risk; • if risk is involved, determine if the importance of the knowledge to be gained warrants allowing the participant to accept the risks; • Oversee protection of rights and welfare of participants. • Assess whether the researcher(s) is/are qualified to conduct research involving human participants.

13. In General • Applies to funded and unfunded research • Submission of a protocol and approval by the IRB is mandatory for any faculty, staff or student who will interact with a human being for purposes of conducting research • Research may not begin before approval from the IRB is given

14. IRB Membership • EachIRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. • Each IRB shall include at least one member whose primary concerns are in the scientific area and at least one member whose primary concerns are in nonscientific areas. • Each IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution. • No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB. • Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession.

15. Howard University IRB Membership Non-affiliated Non-affiliated Leave of absence

16. What type of research requires review? • Research which involves the administration of drugs or other substances to participants • Research involving pregnant women and/or fetuses in utero • Research involving participants with life-threatening physical conditions • Research involving physically intrusive procedures • Research which previous experience (by the particular investigator or other investigators) has shown to create a potential of risk to participants • Research which potentially could put the participant at risk for legal or civil liability or invade a participant's privacy in regard to sensitive aspects of his/her behavior (e.g., illegal conduct, drug use, sexual behavior, alcohol use).

17. What about survey research or questionnaires? • Research which involves the interviewing of participants requires review by the IRB for several reasons; • The IRB must insure the risks do not outweigh the benefits of this research • The IRB must review potential questionnaires and items for inappropriate or potentially harmful items • Certain populations may be at risk for psychological harm (for example; crime/rape victims, Post traumatic stress disorder (PTSD), etc. • The investigator must be qualified to administer these items. • Potential risk of disclosure of identity/confidentiality

18. What types of Research could possibly be exempted? • Research in which the risks of harm reasonably anticipated are not greater than those ordinarily encountered in daily life or during the performance of routine procedures in education and/or in the practice of psychology and medicine • Research on the effectiveness of educational, classroom, and/or instructional strategies, provided that these strategies are familiar, and nonintrusive in their implementation • Research using educational tests (cognitive, diagnostic, aptitude, achievement) if participants' identities are thoroughly protected • Research using survey procedures or interview procedures where participants' identities are thoroughly protected and their answers do not participant them to criminal and civil liability • Research involving the collection or study of existing data, documents, records, specimens, or other products, if these sources are publicly available or the information is recorded by the investigator in such a manner that the participants cannot be identified directly or indirectly. • Remember – The IRB, not the investigator, decides upon the exemption status of a protocol

19. Some research can not be exempted!!!!

20. Socio-behavioral research? • Regarding Laud Humphreys Tea Room Sex Research…. • There was considerable public outrage as well. Journalist Nicholas von Hoffman, who was given some details of the case by one of the angered members of the Sociology Department, wrote an article about Humphreys' research and offered the following condemnation of social scientists: "We're so preoccupied with defending our privacy against insurance investigators, dope sleuths, counterespionage men, divorce detectives and credit checkers, that we overlook the social scientists behind the hunting blinds who're also peeping into what we thought were our most private and secret lives. But there they are, studying us, taking notes, getting to know us, as indifferent as everybody else to the feeling that to be a complete human involves having an aspect of ourselves that's unknown."

21. Considerations • Confidentiality of Information - The confidentiality of the human participants is typically the most important factor in determining whether a research proposal is exempt from further review.  • One University states that “…an investigator must not maintain any form of linkage in order to go back and review the record at a later time. If linkage between the data and the participant must be maintained, the protocol should be submitted for review.” • Due to the nature of much social science research, the possibility of physical harm to human participants is typically minimal or non-existent.  However, human participants could suffer financial or emotional harm in some circumstances if their individual responses to sensitive questions became public knowledge.  • As an example, if a participant describes various faults in the management practices of their organization as part of a research survey and if their identifying information is later associated with their responses then they may face retribution by their managers.  To avoid any possibility of this type of problem the confidentiality of the participant’s responses must be maintained and the measures taken by the researcher to protect this confidentiality must be fully delineated in the IRB Research Protocol.

22. Examples of confidentiality statements… • “Strict confidentiality will be maintained at all times.  New employees and their project managers will be given numbers for tracking purposes.  Contact records used for linking the names of the new employees and their project managers to their tracking numbers will be deleted at the conclusion of the study.  During the study, the contact records will be maintained in one computer location protected by password and one disk backup stored in a government-classified safe.  All reporting will be in the aggregate; names or colleges will not be used to identify individuals.”

23. Example… • “Information obtained in this study will be strictly confidential unless disclosure is required by law.  Participants will be assigned a study number, and this number, rather than the participants’ names, will be recorded at the time of interviews.  Only the study investigator will have a record of which person has been assigned what number and this information will be secured in a locked filing cabinet.  Participant names will not be used in the reporting of information in publications or conference presentations.  The results of the study will be reported in terms of the various treatment groups, not in terms of individuals.  Thus anonymity and confidentiality will be protected.”

24. Informed Consent • Use of Informed Consent Forms • The participation by human participants in any research project must be consensual.    • “…no investigator may involve a human being as a participant in research, as defined in this policy and procedure manual, unless the investigator has obtained the participant's informed consent. The process of informed consent is constituted by two essential elements: (1) the participant has the information he or she requires to make an effective decision, and (2) the participant's participation is not coerced, i.e. his or her consent is voluntary.”

25. Informed Consent Process • While this requirement usually results in the use of an Informed Consent Form in the proposed research, the requirement for human participants to provide their informed consent does not necessarily require the participant to execute a document as proof of their consent.  The IRB may approve a consent procedure which does not include, or which alters, some or all or the elements of informed consent, or waive the requirement to obtain informed consent provided the IRB finds and documents: • The research involves no more than minimal risks • The rights and welfare of participants will not be adversely affected • The research could not practicably be carried out without the waiver or alteration • Whenever appropriate, the participants will be provided with additional pertinent information after participation

26. IRB Process • Review the IRB website and submit a signed application (including your faculty mentor) http://www.huirb.howard.edu/apps.htm • Dissertations and Theses require submission of committee approval • The IRB will review at the next scheduled meeting (every other week) and provide one of the following recommendations; • Approve • Amend • Reject • Table • Conduct your research project and meet the requirements for responsible conduct of research • Submit required reports and documentation

27. Summary…Take home message • The IRB is a key element in the conduct of human participant research at the University. • But, it is the primary responsibility of the IRB to safeguard the rights and safety of human participants. It is not necessarily the role of the IRB to expedite research at the University at the expense of safety and human rights.

28. References • http://muse.jhu.edu/journals/journal_of_health_politics_policy_and_law/v025/25.5merz.html • desu.edu/research/osp/forms/IRBpresentation.ppt • education.ua.edu/ncate/documents/IRB%20Fall%202005%20update.ppt • http://web.missouri.edu/~bondesonw/Laud.html

29. Isn’t the IRB Great?!?!? I love the IRB