The Human Subjects Committee

1. The Human Subjects Committee An Overview of its Functions

2. A Brief History ofUnethical Research Understanding the motivation behind research ethics boards

3. A History of Human Subjects Research • 1st Century BC: Cleopatra has servants impregnated and then executed to study fetal development • 1796: Jenner injects 8-yr-old boy with cowpox & then smallpox to test his vaccine • 1840s: Simms (“father of gynecology”) performs experimental surgeries on slave women without anesthetic. Most of these women died from subsequent infections.

4. Human subjects history, cont’d • 1900: Walter Reed injects Spanish immigrants w/ yellow fever, paying $100 to survivors & $200 if they contract the disease • 1919-1922: Testicular transplant experiments on 500 San Quentin prisoners • 1939: Dr. W. Johnson (prominent speech pathologist) use psychological pressure to cause institutionalized orphans to stutter.

5. Human Subjects History, cont’d • 1940s: Chicago doctors infect 400 prisoners with malaria to help develop treatments (part of war effort) • 1940s: Jews in German prison camps used in various medical experiments (part of war effort) • 1946-1953: Atomic Energy Commission study involves feeding radioactive breakfast cereal to mentally disabled Massachusetts school children

6. Human Subjects History, cont’d • 1956: Dr. Albert Sabin tests experimental polio vaccine on 133 prisoners in Ohio • 1962: Stanley Milgram conducts obedience research at Yale University • 1990: FDA grants waiver of Nuremberg Code for use of unapproved drugs & vaccines in Operation Desert Shield • 1997: US-sponsored, placebo-controlled HIV/AIDS research withholds treatment from infected, pregnant African women

7. Patterns in Unethical Research • Research subjects are often members of vulnerable groups • E.g., prisoners, immigrants, educationally or economically disadvantaged, those desperate for healthcare or other services. • Subjects often have not given consent that is (a) fully voluntary or (b) fully informed. • Researchers often do not do enough to minimize the risks to subjects.

8. The Tuskegee Syphilis Study • 1932 – 1972: US Public Health Service studied 399 black men in late stages of syphilis. Subjects were told they were receiving treatment, but they didn’t. • 28 subjects died of syphilis, 100 died of related complications, 40 of their wives were infected, 19 of their children born w/ congenital syphilis. • Deliberate deception, no concern for subjects’ welfare.

9. Human Subjects History, cont’d • 2005: At the request of chemical companies, the federal Environmental Protection Agency (EPA) proposes exposing infants and pregnant women to higher levels of insecticides than previously allowed. The agency states that these studies will not be subject to the usual federal research guidelines. • Research done at the urging of manufacturers hoping to increase sales.

10. Determining whether research is ethical: • Social or scientific value: Will it produce benefits? • Scientific validity: Is the research well designed? Are subjects selected fairly? Are the investigators competent? • Favorable risk/benefit ratio: Are the risks worth taking? • Independent review: Do others regard it as acceptable?

11. Determining whether research is ethical, cont’d • Informed consent: Do potential subjects understand the procedures and risks? Do they freely volunteer to participate? • Respect for potential and enrolled subjects: • Permit subjects to withdraw from research • Protect privacy • Inform subjects of all risks and benefits • Inform subjects of results • Maintain welfare of subjects

12. Benefits of Research • The moral assessment of research typically focuses on the ratio of harms and benefits produced. Benefits include: • Contributions to scientific knowledge • Medical or psychological benefit to subjects • Benefits to other people (including future generations) • Compensation (material benefits) for subjects (i.e., payment for participation)

13. Harms of Research Harms (and risks of harm) of research include: • Using subject’s time (particularly important for terminally ill subjects) • Psychological harm • Physical harm • Disclosure of sensitive data could result in subject’s loss of employment, marital stress, stigmatization, loss of insurance, criminal investigation, etc.

14. Research & Distributive Justice • The benefits & burdens of research should be equitably distributed. • Impermissible for subjects in a poor developing nation to bear the burdens of research that primarily benefits those in wealthy industrialized nations. • Subject recruitment should be equitable, not exploiting vulnerable populations. • Equitable subject enrollment also tends to result in better data (more representative samples).

15. Rules & Agencies Governing Humans Subjects Research in the U.S. • Regulations implemented by 17 federal agencies, known as the “common rule,” require approval for all human research. • Office of Human Research Protection (OHPR) is part of the Dept of Health & Human Services (DHHS). • Also human subject protection offices within the Food & Drug Administration (FDA) and National Institutes of Health (NIH).

16. The Belmont Report • The National Research Act (1974) established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This Commission wrote the Belmont Report (1979), which lays out the ethical guidelines that should guide research on humans. • Fundamental moral principles: Respect for Persons (which is equivalent to Respect for Autonomy), Beneficence/Nonmaleficence, and Justice. • These are applied to informed consent, assessment of risks & benefits, and selection of subjects.

17. Institutional Review Boards (IRBs) • Human subjects research involving any federally-funded institution must first be approved by that institution’s IRB. • At Idaho State University, the IRB is the Human Subjects Committee. • Unlike other university committees, no one on campus has authority over the HSC. • Only a federal judge can overturn its rulings.

18. The Structure of an IRB • At least 5 members, drawn from different backgrounds. • ISU’s Human Subjects Committee: 10 members • Must include a scientist, a member of the medical profession, an ethicist, and a non-affiliated (community) member. • IRBs should also reflect the gender, racial, and ethnic diversity of the community in which the research is taking place. • At ISU, members are recommended by the Dean of Research, and appointed by the President of the University. • Members serve (renewable) 3-year terms.

19. The Function of the IRB • Research involving humans must be cleared by the IRB before it begins. • Many granting agencies require IRB documents before providing funding. • Some journals & conferences require IRB documents before accepting articles. • The IRB may prevent research from beginning, or stop research once it has begun if there is evidence that proper procedures have not been followed or that subjects have been wronged by the research process. • The IRB also monitors (and may approve or disapprove) any changes to the research protocol.

20. What if the IRB isn’t working? • If an IRB does not function properly, the federal government may stop all research at that institution. • In 1990, ISU was threatened with the loss of all federal funding because of problems with its IRB. • In 1999, all research was stopped at Duke University, the University of Illinois at Chicago, and ten other level-1 research institutions. • Regular oversight & audits…

21. Who Must Go Through ISU’s IRB? • Any researcher – faculty, student, or administrator – who is affiliated with ISU. • Doesn’t matter where the research is being carried out. • Doesn’t matter whether ISU is paying for the research.

22. What does NOT need to go through the IRB? • Quality assurance & outcomes assessment • Provided the purpose is ONLY to provide feedback for monitoring and improvement. • If you’re generalizing data to draw conclusions about programs in general, then it’s research – IRB approval required! • Some oral history projects • IRB approval required only if the information being gathered could pose risks (e.g., breach of confidentiality leads to legal action, loss of insurance, marital strife, etc.)

23. What Happens if I Ignore the Committee? • Variety of steps taken by the university, including (but not limited to): • Degree denied or revoked • Expulsion • Other actions (could include being fired/dismissed) • Variety of steps taken by federal agencies, including (but not limited to): • $50,000 fine and/or 3 years in prison • Ineligible for federal research funding

24. Do I qualify for a Certificate of Exemption? • Some research activities are exempt from the full HSC approval process. These guidelines are established by federal law. • Researchers are not permitted to “self exempt.” The Human Subjects Committee (HSC) must issue a Certificate of Exemption. • These decisions are made by the committee chair.

25. Exemption is NOT available if: • Vulnerable populations are involved. • The research uses medical records that include identifying information. • Research involves observing the public behavior of minors. • Research exposes subjects to discomfort, risk, or harassment beyond levels experienced in everyday life. • Research involves deception.

26. Types of HSC Review • Full Review: Proposal examined by entire board. • Required when risks are greater than minimal, or when subjects are vulnerable. • Minimal risk: No more than subjects would encounter in daily life, or in the course of a medical or psychological examination. • Ongoing debate about how best to interpret this definition. • Submit 12 copies of form HS-1

27. Vulnerable Populations: • Fetuses & human in vitro fertilization • Includes the fetus in utero and ex utero. • Also includes dead fetuses, fetal material, & the placenta. • Women of child-bearing potential (this applies only to early-phase drug trials) • Pregnant women • Minors (< 18 yrs) • Elderly (> 65 yrs)

28. Vulnerable Subjects, cont’d • Economically or educationally disadvantaged groups • People with cognitive disabilities • Terminally ill patients • Emergency room patients • Institutional residents • Non-English speakers • Prisoners (and others in the criminal justice system)

29. Types of HSC Review, cont’d • Expedited Review: Examined by 1 or 2 board members. • Not linked to committee meeting schedule; faster response to investigator. • Permitted only when: • No vulnerable subjects • Minimal risk • Submit 3 copies of form HS-1

30. Types of HSC Review, cont’d • Certificate of Exemption: Available for certain, narrowly-defined research activities. • Only minimal risk. • Category 1: Assessing existing educational practices • Category 2: Anonymous surveys • Category 4: Analysis of de-identified existing data • Submit 3 copies of form HS-7 • Determination made by HSC chair

31. Names Geographical info Elements of dates (except year) Ages over 89 yrs Telephone and FAX numbers Email addresses Social security # Medical record or prescription # Account number Health plan beneficiary number Certificate or license number Serial or license plate numbers Web URLs Device identifiers IP address numbers Full face or comparable photos Any other unique identifying numbers To de-identify information,remove all of the following:

32. Dual Role Problems • Just because you have authority over people or access to their records as part of your job does not mean that you may use this in your role as a researcher. • This raises concerns about confidentiality, voluntariness, risk of retribution, etc. • When dual roles cannot be avoided, they must be handled with great care.

33. What Decisions does the HSC Make? • Protocols submitted for expedited review: • Proposal could qualify for certificate of exemption • Approved as submitted • Approved with minor modifications • Modifications must be resubmitted & approved by the HSC chair before research may begin • Remand the proposal for full review. • Usually because the research involves a vulnerable population or greater than minimal risk.

34. Decisions about Full Review Proposals • Approved as submitted • Approved with minor modifications Again, the proposal must be resubmitted & the HSC chair must approve the modifications before research may begin • Approved with major modifications Revised proposal goes back to full committee. • Approval denied Rare, but it can happen

35. Term of HSC Approval • The HSC’s approval of research is for the term of one year. Research lasting longer than that must be resubmitted annually. • Research INCLUDES the data analysis process. • Researchers must report any adverse reactions (harms to subjects). • Any modifications to the protocol must be approved by the HSC before any changes are implemented.

36. Informed Consent Issues • Make sure potential participants can understand the information • Use an appropriate reading level (avoid technical terms) • Translation when required • Don’t allow subjects to cross out any parts of the consent form • It was approved as a whole. Changing the form or the procedure may change the risks.

37. More Informed Consent Stuff: • For important components of the consent form, have subject initial paragraphs • Consider using “participant” or “volunteer” instead of “subject” in the consent form • Consider breaking the text of the form into sections, each with a clear heading • Keep it short, but don’t compromise clarity • Have a 1-page summary for long consent forms

38. What goes into the Consent Form? • Lay-language summary of project • Clear, complete description of procedures • What will happen to me? • How long will it take? • Risks & discomforts • Benefits • Don’t assume an experimental therapy or intervention works – that’s what the research is supposed to determine • Alternatives to participating in study

39. Consent Form Contents, cont’d • What will happen to information (or samples) after they are collected? • Any reimbursement for participation? • Response to research-related injuries? • Researchers have a moral obligation to make reparation for any harms • Subjects must not be asked to waive their legal rights. You may only state the institution’s limits on what it will do voluntarily for injured subjects.

40. Consent Form Contents, cont’d • Whom can I contact with questions about this study? • What do I do if I decide to withdraw from the study? • Make clear to subjects that they are permitted to withdraw at any time • How long will this study last? • How many participants will be enrolled? • How will my confidentiality be protected?

41. Upcoming Change: • Some researchers will soon be required to complete an on-line research ethics course. • Takes 3 – 4 hours; covers all important issues • Managed by FDA, DHHS • Email completion certificate to IRB • This will be required of all “key personnel” in studies involving significant risk.

42. Paper Reduction Changes! • Instead of sending 12 copies of form HS-1, soon researchers will be asked to submit 3 copies and a CD-ROM. • If we can get electronic signature requirements settled, this may soon be entirely on CD-ROM (or other electronic filing method).

43. Reporting Adverse Events • You MUST promptly report “any unanticipated problems involving risk to subjects or others.” • Address the following: • Expected or unexpected event? • How serious is the event? • Death? Life threatening? In-patient hospitalization? ER visit? Causes disability, cancer, or birth defect? Overdose? • Is the event related to the research interventions?

44. The Most Common Mistakes • Failure to sign the protocol. Student research requires faculty advisor signature. • Inadequate description of methods. • Literature review • Subject contact & selection methods (inclusion/exclusion criteria) Who decides whether subjects meet these criteria? • Number of subjects (or reasonable estimate) • Details of what will happen to subjects

45. More Common Mistakes: • Underestimating risks or exaggerating benefits: If there’s no benefit to participants, then say so. • Failure to provide alternative activities for classroom research • Inadequate provision for storing or disposing of data Where will it be kept? Who will have access to it? How long will it be kept? How will it be disposed of? • Inadequate consent documents

46. Still More Common Mistakes: • Failure to include questionnaire For open-ended interviews, qualitative research, etc., include a detailed description of the starting point for the interview and the topics to be covered. • Failure to include permission letters from research sites (or owner of data sets, etc.) • Consent letters incomplete or not readable by potential subjects Include contact information for the PI