1. Supporting the Needs of Human Subjects in Research Carol Johnston, Chair, Bioscience IRB Mark Roosa, Chair, Social Behavioral IRB

2. Overview Historical Perspective IRB/Compliance Office Priorities Review Process Questions and Answers

3. 20 th Century Research 1972 Syphilis Study Exposed 1966 The Beecher Article (NEJM) 1932 Tuskegee Syphilis Study begins Kefauver-Harris Amendments Food, Drug and Cosmetic Act 1962 Common Rule 1991 1940’s Nazi Experiments Clinton Apology 1997 OPRR shuts down programs 1999 Informed consent is essential. Research should be based on prior animal work. The risks should be justified by the anticipated benefits. Only qualified scientists must conduct research. Physical and mental suffering must be avoided Nuremberg Code 1947 response to the Thalidomide tragedy Declaration of Helsinki 1964 Reinterpreted the Nuremberg Code for medical research with therapeutic intent Journal requirements that research be conducted accordance with the Declaration Sets the stage for the implementation of Institutional Review Boards (IRB) Belmont Report 1979 Identifies three basic ethical principles that underlie human subject research: Respect for persons Beneficence Justice Compliance by research institutions Record-keeping,

4. More Significant Events 1991 199619971999 20012006 Common Rule 1991 Nicole Wan dies at Rochester 1996 volunteer subject in a study of the role of airborne chemicals in lung cancer dies two days after she underwent a bronchoscopy President Clinton apologizes to PHS Syphilis study survivors Jesse Gelsinger dies at U Penn the first person publicly identified as having died in a clinical trial for gene therapy - he was 18 y old OPRR shuts down U Penn Ellen Roche dies at Johns Hopkins a 24-year-old technician at the university's asthma and allergy center and trial volunteer died from lung failure OHRP suspends JH federally funded research Eight healthy male volunteers were admitted to the critical care unit at Northwick Park and St. Mark's Hospital in London with multiorgan failure following the first day of a double-blind, randomized, placebo-controlled phase 1 study of the safety of a novel monoclonal antibody.

5. Universities, Hospitals Shut Down Mar 1999 West Los Angeles Veterans Administration Medical Center May 1999 Duke University Medical Center Aug 1999 University of Illinois Sep 1999 University of Colorado Sep 1999 University of Pennsylvania Jan 2000 Virginia Commonwealth University Jan 2000 University of Alabama at Birmingham Jun 2000 University of Oklahoma – Tulsa Jun 2001 Johns Hopkins Medical University August 2008 – Indiana University voluntarily moves IRB reviews to Indianapolis campus

6. Where is ASU? 3 Federal Audits at ASU in recent years http://www.hhs.gov/ohrp/detrm_letrs/YR07/jul07c.pdf Havasupai Lawsuit

7. Compliance Office/IRB Priorities Protect human subjects Provide a service to researchers Prevent ASU from experiencing sanctions

8. ASU Human Subjects Review All human subjects research must be reviewed & approved prior to data collection Exempt Studies >900 <25 Expedited Review >500 ~225 Full Board 50 33 REVIEW TIME DEPENDS UPON THE TYPE OF STUDY! Generally the review takes 1-6 weeks from receipt in office! Social/Behavioral Biosciences

9. The Review Process Mission To protect the rights and welfare of research subjects Reviewers’ quandary: Will a change in the research protocol likely improve the welfare of research subjects to a meaningful degree?

10. Criteria for IRB Approval Introduction, specific aims, background  Are the specific aims clearly specified?  Are there adequate preliminary data to justify the research?  Is there appropriate justification for this research? Scientific design  Is the scientific design adequately described and justified?

11. Criteria for IRB Approval – continued Inclusion/exclusion criteria  Are inclusion and exclusion criteria clearly specified and appropriate?  If women, minorities, or children are included or excluded, is this justified?  Is the choice of subjects appropriate for the question being asked?  Is subject selection equitable? Recruitment of subjects  Are the methods for recruiting potential subjects well defined?  Is the individual performing the recruitment appropriate for the process?  Are all recruitment materials submitted and appropriate?

12. Criteria for IRB Approval – continued Research procedures  Are the rationale and details of the research procedures accurately described and acceptable?  Are the individuals performing the procedures appropriately trained? Is the location for the procedures acceptable?  Are there adequate plans to inform subjects about specific research results if necessary (e.g., clinically relevant results)? Data analysis and statistical analysis  Is the rationale for the proposed number of subjects reasonable?  Are the plans for data and statistical analysis defined and justified?

13. Criteria for IRB Approval – continued Potential risks, discomforts, and benefits for subjects  Are the risks and benefits adequately identified, evaluated, and described?  Are the potential risks minimized and likelihood of benefits maximized?  Is the risk/benefit ratio acceptable for proceeding with the research? Compensation and costs for subjects  Is the amount or type of compensation or reimbursement reasonable?  Are there adequate provisions to avoid out-of-pocket expenses by the research subject?

14. Criteria for IRB Approval – continued Privacy and confidentiality  Are there adequate provisions to protect the privacy and ensure the confidentiality of the research subject?  Are there adequate plans to store and code the data?  Is the use of identifiers or links to identifiers necessary, and how is this information protected? Consent document  Are the Federally mandated components addressed?  Are these components clearly explained in laymen's terms?

15. Questions ??

16. Contact Information Susan Metosky, IRB Administrator (480) 727-0871 Susan.Metosky@asu.eduSusan.Metosky@asu.edu Alice Garnett, IRB Specialist (480) 965-4796 Alice.Garnett@asu.eduAlice.Garnett@asu.edu Debra Murphy, Director for Research Compliance (480) 965-2179 Debra.Murphy@asu.eduDebra.Murphy@asu.edu