Office of Research Integrity Assurance All rights reserved GTRC Presented by Georgia Institute of Technology Institutional Review Board Presented by Melanie Clark, CIP Associate Director Office of Research Integrity Assurance

Office of Research Compliance All rights reserved GTRC Significant Events PHS Syphilis Study, formerly “Tuskegee Study PHS Syphilis Study, formerly “Tuskegee Study ” Nuremberg Code 1947 U.S. Scandals Henry Beecher: "Ethics and Clinical Research" Public Health Service Policy Adopting IRBs Declaration of Helsinki Declaration of Helsinki Stanford Prisoner Study (1971) Stanford Prisoner Study (1971) PHS “Tuskegee Study” Revealed (1972) PHS “Tuskegee Study” Revealed (1972) National Research Act & 45 CFR 46 National Research Act & 45 CFR 46 Belmont Report (1979) Belmont Report (1979)

Office of Research Compliance All rights reserved GTRC

Office of Research Compliance All rights reserved GTRC Military Tribunal led to Nuremberg Code Voluntary consent Anticipated scientific benefits Benefits outweigh risks Animal experiments first No intentional death or disability Subjects may withdraw at anytime Investigators must be qualified Investigators will stop if harm occurs

Office of Research Compliance All rights reserved GTRC

Office of Research Compliance All rights reserved GTRC 1950s: Willowbrook State School Staten Island, New York 1960s: Jewish Chronic Disease Hospital Cancer Experiments

Office of Research Compliance All rights reserved GTRC Milgram Study Yale University

Office of Research Compliance All rights reserved GTRC Stanford Prison Experiment

Office of Research Compliance All rights reserved GTRC 1932, Public Health Service study, in collaboration with the Tuskegee Institute in Macon County, Alabama, undertook a study of untreated syphilis in hopes of justifying treatment programs for blacks. 600 black men (399 with syphilis, 201 without) were told they had "bad blood," a local term used to describe syphilis, anemia, and fatigue. Penicillin, treatment of choice, was discovered in 1940s but was withheld. In exchange for taking part in the study, the men received free medical exams, free meals, and burial insurance. Although originally projected to last 6 months, the study actually went on for 40 years.

Office of Research Compliance All rights reserved GTRC Ethical Principles and Guidelines for the Protection of Human Subjects of Research Respect for Persons Individual autonomy Protection of individuals with reduced autonomy Beneficence Maximize benefits and minimize harms Justice Equitable distribution of research costs and benefits The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research April 18, 1979

Office of Research Compliance All rights reserved GTRC Significant Events Common Rule 1991 Nicole Wan dies at Rochester 1996 President Clinton apologizes to PHS Syphilis study survivors Jesse Gelsinger dies at U Penn VCU Twins Study OPRR shuts down LA VA Medical, Duke, U Ill, U Colo, U Penn OPRR shuts down VCU, UAB, U Okla OPRR reorganized as OHRP, moved to Cabinet level and Director replaced, June 2000 Ellen Roche dies at Johns Hopkins; OHRP suspends JH federally funded research Secretary's Advisory Committee on Human Research Protections replaces National Human Research Protections Advisory Committee

Office of Research Compliance All rights reserved GTRC 1999: Jesse Gelsinger & University of Pennsylvania 18-year old volunteer in U Penn’s gene therapy study of partial omithine transcarbamylase deficiency (OTC)

Office of Research Compliance All rights reserved GTRC 2001: Ellen Roche & Johns Hopkins Healthy lab technician volunteered for asthma study of hexamethonium bromide. Respiratory effects of hexamethonium bromide were not known to investigator prior to study. Previous participant had respiratory problems, solution was changed without IRB being informed. Johns Hopkins forced to halt $300 million in medical research Ellen Roche died. Compensation for her participation: $365. Johns Hopkins settled out of court with her family.

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Office of Research Compliance All rights reserved GTRC Oh No! The Feds Shut Us Down

Office of Research Compliance All rights reserved GTRC What Happens When the Research Enterprise is Shut Down All federal research funding involving human subjects suspended (payroll, operations, etc.) All experiments halted (except to treat enrolled subjects on a case-by-case basis) IRB must re-review all protocols Millions of dollars in lost revenue and expenses to bring institution into compliance

Office of Research Compliance All rights reserved GTRC

Office of Research Compliance All rights reserved GTRC What is an IRB? Faculty committee with the purpose of reviewing research activities involving human participants Constituted in accordance with federal law: Minimum of five members Community representation Scientific and non-scientific members Adequate expertise to review the proposed work Consultants, when needed

Office of Research Compliance All rights reserved GTRC What is a human subject? As defined by 45 CFR 46 Is a living individual about whom an investigator obtains either: Data through intervention or interaction with the individual; or Identifiable private information

Office of Research Compliance All rights reserved GTRC What is research? Research: As defined by 45 CFR 46, "a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge"

Office of Research Compliance All rights reserved GTRC Categories of Research Exempt Expedited Full

Office of Research Compliance All rights reserved GTRC What you need to submit IRB application IRBWISE Project description Consent/Assent/Parental Permission All recruitment flyers & scripts Human Subjects Training Certificate Questionnaire, surveys or interview guides

Office of Research Compliance All rights reserved GTRC § General requirements for informed consent Statement that it is research Purpose & procedures Health and financial risk Compensation/costs Confidentiality In case of injury Subjects rights Appropriate reading level

Office of Research Compliance All rights reserved GTRC Anything Else? All Amendments must be submitted to IRB for review and approval prior to commencement. Any change to the protocol or consent form All Adverse Events must be submitted for IRB review even if they are not study related.

Office of Research Compliance All rights reserved GTRC Principal Investigator’s RESPONSIBILITIES Obtain approval prior to start of research Inform IRB of: Adverse events Changes in protocol Violations Continuing review request Obtain consent prior to enrolling subjects

Office of Research Compliance All rights reserved GTRC Case Study “Check List” Johns Hopkins University Intensive Care Units in State of Michigan Office for Human Research Protections

Office of Research Compliance All rights reserved GTRC Important Information IRBWISE information Human Subjects Training (CITI) Policy and Procedures Consent templates

Office of Research Compliance All rights reserved GTRC Contact Information Melanie Clark, Associate Director Kelly Winn, Research Associate Barbara Henry, Director Dennis Folds, IRB Chair