Supporting the Needs of Human Subjects in Research Carol Johnston, Chair, Bioscience IRB

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. 20th Century Research OPRR shuts down programs 1999 Clinton Apology 1997 Common Rule 1991 • Compliance by research institutions • Record-keeping, • Identifies three basic ethical principles • that underlie human subject research: • Respect for persons • Beneficence • Justice Belmont Report 1979 1972 Syphilis Study Exposed 1966 The Beecher Article (NEJM) 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) Kefauver-Harris Amendments Food, Drug and Cosmetic Act 1962 • response to the Thalidomide tragedy • 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 1940’s Nazi Experiments 1932 Tuskegee Syphilis Study begins

4. 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 More Significant Events Eight healthy male volunteers were admitted tothe critical care unit at Northwick Park and St. Mark'sHospital in London with multiorgan failure following the first day of a double-blind, randomized, placebo-controlled phase 1 studyof the safety of a novel monoclonal antibody. 1991 1996 1997 1999 2001 2006

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

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.edu Alice Garnett, IRB Specialist(480) 965-4796 Alice.Garnett@asu.edu Debra Murphy, Director for Research Compliance (480) 965-2179 Debra.Murphy@asu.edu