Human Subjects Research

1. RESPONSIBLE CONDUCT IN RESEARCH(supported in part by a grant from the National Postdoctoral Association) Human Subjects Research created April, 2009

2. Short pre-test • Presentation Objectives • NIH Comment • background • regulation, policy and Federal Assurance • considerations • SIT institutional processes involved in animal research • ethical considerations • available resources • Reference Material • Faculty Presentation • Case Study and Discussion • Short post-test Presentation content RCR – Human Subjects created April, 2009

3. NIH COMMENT • “Investigators must balance their interest in gathering data and answering research questions with society’s mandate to protect the rights and safeguard the welfare of research subjects.” (1)National Institutes of Health • “Society has granted a conditional privilege to perform research on human beings……the condition is that it must be conducted in a way that puts the rights and welfare of human subjects first.” (1)National Institute of Health RCR – Human Subjects created April, 2009

4. Nuremberg Code of 1947 (2) • result of medical experiments performed in German concentration camps during World War II. “…The great weight of evidence before us it to the effect that certain types of medical experiments…conform to the ethics of the medical profession generally…however…certain basic principles must be observed in order to satisfy moral, ethical and legal concepts…” • Declaration of Helsinki adopted in 1964 (3) • adopted by World Medical Association and forms the basis of most subsequent documents addressing human subjects research. Introduced concept of oversight by an ‘independent committee’ which became a system of Institutional Review Boards • Belmont Report (4) • culmination of the work a national commission began in 1974. It was adopted by NIH in its entirety. BACKGROUND RCR – Human Subjects created April, 2009

5. Regulation, policy and federal assurance 45 CFR 46 – Protection of Human Subjects -- http://www.hhs.gov/ohrp/documents/OHRPRegulations.pdf(5) RCR – Human Subjects Stevens’ Institutional Policy “Human Subjects/IRB” Stevens’ Federal Wide Assurance with National Institutes of Health, Office for Human Research Protections (NIH OHRP) – FWA00014433 Stevens’ IRB Registration with NIH/OHRP – IORG0004982 created April, 2009

6. considerations • The three most often cited concepts associated with human subjects research are: • Autonomy • Beneficence • Justice RCR – Human Subjects created April, 2009

7. AUTONOMY • (voluntary informed consent) • > Controversy in Berlin Led to Ethical Code & Inf. Consent • Dr. Albert Neisser “treated” Berlin prostitutes without their knowledge using serum from recovering syphilis patients in the belief he was discovering a cure • Caused epidemic of syphilis among prostitutes & their customers. • Rudolf Virchow recommended code for research with humans to prevent future breaches of ethics. • > Berlin Code of 29 Dec 1900 • Required unambiguous consent • Required study be conducted or directed by the institute medical director • Excluded use of minors or incompetent subjects • Req. documentation of fulfillment of code requirements in subjects records • Did not interfere with standard diagnostics, care and prophylaxis Considerations (cont.) RCR – Human Subjects (Slide information taken from “Time Passages: Local Military Medical History Connections” Art Anderson MD, Office of Human Use and Ethics, USAMRID) (6) created April, 2009

8. BENEFICENCE • (good science & favorable benefit to risk ratio) • > 1777 Variolation* of the Troops Helped Win the Revolutionary War • George Washington's experiences during the French and Indian War convinced him that Smallpox was a bar to success of the Revolution • Washington proclaimed smallpox to be his ““most dangerous foe;””and, by 1777 he had all his soldiers variolated • He also ordered all new recruits to be variolated as soon as they enlisted • Fortunately, in this case, the ends of these actions did justify the means • (Slide information taken from “Time Passages: Local Military Medical History Connections” Art Anderson MD, Office of Human Use and Ethics, USAMRID) (6) considerations RCR – Human Subjects created April, 2009

9. JUSTICE (7) • (equal opportunity to participate and to not participate) • > “Tuskegee Study of Untreated Syphilis in the Negro Male” • study conducted by the Public Health Service between 1932-1972 • human subjects were 399 poor, mostly illiterate, African American sharecroppers • study for research related to the natural progression of the disease if left untreated • researchers failed to treat patients appropriately after 1940s validation of penicillin as effective cure for syphilis • participants were prevented from accessing syphilis treatment programs available to other people in the area • a leak to the press in 1972 resulted in its termination considerations RCR – Human Subjects created April, 2009

10. SIT Institutional processes in HUMAN SUBJECTS research Often, human subjects research is done in conjunction with a sponsored research project. Proposals for sponsored projects should be submitted to the Faculty Support Center Protocols for human subjects research as part of a sponsored project are separate activities. Human subjects protocols should be submitted to the IRB RCR – Human Subjects Investigator must initiate and submit the human subjects research protocol to the IRB – understanding sponsor requirements for approvals and proposal deadlines Funding for sponsored projects involving the use of human subjects WILL NOT be enabled until IRB approval is received and verified in OSR created April, 2009

11. Timeline of events NIH, the most common federal agency to which PI’s would submit research proposals that might include human subjects typically has three submission cycles each year. The timeline shown below is offered to help with planning the preparation and submission of various required materials: RCR – Human Subjects SIT IRB review process Feb. 5 Proposal Deadline = mid January FSC Deadline Mar-Apr = protocol submitted to SIT IRB Sep-Oct Council Review = full SIT IRB approval submitted for JIT PROPOSAL SUBMISSION Cycle 1 Cycle2 Cycle 3 Feb 5 June 5 Oct 5 PEER REVIEW Cycle 1 Cycle 2 Cycle 3 Jun-Jul Oct-Nov Feb-Mar COUNCIL REVIEW Cycle 1 Cycle 2 Cycle 3 Sep-Oct Jan-Feb May-Jun EARLIEST FUNDING Cycle 1 Cycle 2 Cycle 3 Dec. April July PROPOSAL SUBMISSION Cycle 1 Cycle 2 Cycle 3 Feb. 5 June 5 Oct. 5 createdApril, 2009

12. Be aware of the need for Institutional Review Board review and approval • -- ‘exempt’ is a category, it does not imply an investigator is ‘exempt’ from the application process Ethical considerations RCR –Animal Research (8) created April, 2009

13. Office of Sponsored Research • Can provide assistance and direction for investigators contemplating animal research • 201.216.8762 – Barbara DeHaven, Executive Director • Institutional Review Board • Duly constituted committee at Stevens charged with the review and approval of all human subjects research done at the Institute • 201.216.5032 – Dr. Zvi Aronson, IRB Chair • Office of Institutional Risk, Compliance and Audit • Chuck Shaw – 3rd Floor Howe Center – 201.216.8568 Available resources RCR – Human Subjects created April, 2009

14. Reference material • “Guidelines for the Conduct of Research Involving Human Subjects at the National Institute of Health” http://ohsr.od.nih.gov/guidelines/GrayBooklet82404.pdf • “Nuremberg Code of 1947” http://www.hhs.gov/ohrp/references/nurcode.htm • “The Helsinki Declaration” http://www.cirp.org/library/ethics/helsinki/ • “The Belmont Report” http://ohrp.osophs.dhhs.gov/humansubjects/guidance/Belmont.htm • “45 CFR 46 http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm • “Time Passages: Local Military Medical History Connections” Art Anderson MD, Office of Human Use and Ethics, USAMRID) • http://www.geocities.com/artandersonmd/med_history.pdf • “The Tuskegee Study of Untreated Syphilis in the Negro Male” • http://en.wikipedia.org/wiki/Tuskegee_Study_of_Untreated_Syphilis_in_the_Negro_Male • www.cartoonstock.com RCR – Human Subjects created April, 2009

15. Faculty presentation Dr. Peter Dominick - Asst. Professor, Howe School of Technology Management RCR – Human Subjects created April, 2009

16. Stevens IRB Committee Members • Academic • Zvi Aronson, Ph.D. Industrial/Organizational Psychology • Peter Dominick, Ph.D. Industrial/Organizational Psychology • Patricia Holahan, Ph.D. Organizational behavior • Ann Mooney, Ph.D.Organizational behavior • Medical and Mental Health • Glen Atlas, M.D. Anesthesiologist at UMDNJ • Terence Hannigan, Ph.D. Clinical Psychologist • Vincent Grasso M.D. @ P. Dominick, 2009

17. Stevens IRB activities during past two years • Twelve Submissions in the past two years • Ten accepted with no or minimal revisions • Two were rejected each after two rounds of review @ P. Dominick, 2009

18. When Should You Submit Something to our IRB? • Any studies that will involve human subjects • Medical and biomedical • Social sciences • Psychology • Sociology • Anthropology • Ethics • Management practices • Computer science • Some studies in biology and chemistry @ P. Dominick, 2009

19. The Milgram Studies (1963) • Subjects ostensibly assigned to be “learners” or “teachers” • “Teachers” must administer shocks to “learners” each time they make a mistake • “Learners” and “teachers” located in different rooms • Shocks are painful but not harmful • “teachers” will hear “learners” react to the pain @ P. Dominick, 2009

20. Would you Approve this Study today? • What concerns would you have? • Who do you think might be harmed by this research? • What questions would you ask of the researcher? • Would you reject it? • Might you seek to modify the experiment? @ P. Dominick, 2009

21. The Original Milgram Studies • Original Studies made profound contributions to Social Psychology • 68 percent of “teachers” complied with experimenters instructions and administered 450 volt shocks repeatedly • Also considered the paradigmatic example of why psychology experiments must be reviewed by IRB’s • Many said they “would never be replicated” @ P. Dominick, 2009

22. The Milgram Studies Today • Studies were replicated in 2006 • Stopped at 150 volts instead of 450 volts • Immediate feedback to participants • 15 volt “test shock” • Two step screening process to ensure participants could handle the experience • “Of course, I also needed IRB approval. I knew from my own participation on the IRB that the proposal would be met with concern and perhaps a little fear by the board’s members. . . . To address these concerns, I created a list of individuals who were experts on Milgram’s studies and the ethical questions surrounding this research. I offered to make this list available to the IRB. More important, Steven Breckler, a social psychologist who currently serves as the executive director for science at the American Psychological Association, graciously provided an assessment of the proposal’s ethical issues that I shared with the IRB. “ Jerry Burger @ P. Dominick, 2009

23. Types of Research Programs which May be Exempt • Instructional strategies conducted in established or commonly accepted educational settings • The use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior • Collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if sources are publicly available, or if the information is recorded with complete anonymity • Taste and food quality evaluation and consumer acceptance studies, if: • wholesome foods without additives • food that contains an ingredient that is found to be safe • agricultural chemical or environmental contaminant at or below the level FDA, EPA and or the Food Safety and Inspection Service of the U.S.D.A. deems to be safe @ P. Dominick, 2009

24. Types of Studies Whose Review is Likely to be Expedited • Collection of hair and nail samples • Collection of excreta and external secretions • Recording of data from subject 18 years of age or older using noninvasive procedures • Collection of blood samples in minimal amounts • Collection of dental plaque and calculus • Voice recording • Moderate exercise by health volunteers • Study of existing data • Research on an individual or group behavior that involves no manipulation of the subjects and is not stressful @ P. Dominick, 2009

25. Research Likely to Require Full Review • Most research that involves children, prisoners, pregnant women, fetuses and other vulnerable populations • Research that involves experimental drugs or devices • Research that involves most invasive procedures • Survey research that involves sensitive questions or is likely to be stressful for the subject @ P. Dominick, 2009

26. Stevens Procedures • Contact Zvi Aronson if engaging in any research that involves human subjects • Confidentiality form (Anonymity) • Consent Form (Justice) • Rationale Form (Beneficence) • Brief descriptions of ( usually just a few paragraphs) • key research question • types of participants sought • experimental procedures/protocol (including any deception) • procedures for ensuring confidentiality and subject well-being • Procedures for attaining consent @ P. Dominick, 2009

27. Questions to Ask Yourself • Autonomy • Will people have the opportunity to opt in or out of my research? • Are those involved capable of making an informed decision about participation? • Beneficence • What are the major benefits to be derived from my research? • How do they compare to any risks? • In what ways might people better off because of my study? • Subjects • General population? • Are there other less invasive ways to learn the same things? • Justice • Is this study fair to those who are involved? • Will it deny them other opportunities that may be of benefit to them? • How might they be affected or changed as a result of their experience? @ P. Dominick, 2009

28. Bob is working hard to complete his Master’s degree in the Psychology Department’s program of Research and Related Ethics through the Institute for Social and Humane Ethics at Prestigious University. His thesis focuses on the residual effects of severe psychological trauma throughout a lifetime. Specifically, he’s chosen to focus on Holocaust survivors from World War II. He’s gotten into a significant time crunch as the literature review took longer than anticipated and he had an unexpected family emergency during that same time. He needs interviews with survivors in order to make his data credible but knows he needs to submit a protocol to his institutional IRB for review and approval. That will add an additional two months (minimum) to his timeline that he frankly doesn’t have. Bob is sensitive to his research population and he’ll be careful. He really needs the interview data and decides to go ahead without submitting the protocol for review. Since he’s doing the interviews without IRB approval he decides he doesn’t need to be concerned about the informed consent. Consider the following: CASE STUDY RCR –Human Subjects created April, 2009

29. Q: Who will, or might be affected by Bob’s decision to forego the required IRB application, review and approval process? CASE STUDY(cont.) A: -- The Holocaust survivors -- Bob -- The Institute for Social and Humane Ethics -- Prestigious University RCR –Human Subjects created April, 2009

30. Q: What are the possible consequences of Bob’s decision not to observe the requirement for protocol application, review and approval? CASE STUDY(cont.) A: The Holocaust survivors could definitely be affected as recalling memories of such experiences could be severely distressing, cause panic, or even result in an adverse medical event for this extremely aged population Bob will be affected if it is discovered that he has violated one of the integral tenets of human subjects research. His degree could be in jeopardy and he would be disgraced. There is a likelihood that none of his data would be accepted in support of the thesis. Lastly, the Institute for Social and Humane Ethics would probably be embarrassed……at a minimum RCR –Human Subjects created April, 2009

31. Q: Are there any laws, regulations, or institutional policies that may apply to this situation? CASE STUDY(cont.) A: -- The Nuremberg Code -- The Helsinki Declaration -- The Belmont Report -- 45 CFR 46 -- Prestigious University’s Policy on the inclusion of human subjects in research -- Code of professional ethics of the American Psychological Association RCR –Human Subjects created April, 2009

32. Q: If Bob had submitted the protocol for review as required, what items might the IRB have been concerned with? CASE STUDY(cont.) A: -- Informed Consent * IRB would have wanted adequate description of the benefits and risks for this population * IRB would have wanted a warning that some of the questions might cause distress and that subjects could stop at any time * IRB would have wanted to ensure Bob had planned for the possibility that recalling the subject matter content for some of the subjects might even result in an adverse medical event and what were his plans if that happened * IRB would have required Bob to include resources for subjects who might need psychological assistance as the result of recalling repressed memories RCR –Human Subjects created April, 2009

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