Alphabet Soup (U.S. Federal Agencies): CDER: Center For Drug Evaluation and Research; CBER: Center For Biologics Evaluation and Research; CDRH: Center For Devices and Radiological Health; FDA: Food and Drug Administration (part of DHHS); DHHS: Department of Health and Human Services; OHRP: Office For Human Research Protections (part of DHHS); ORI: Office of Research Integrity (part of DHHS); OIG: Office of the Inspector General
Basic Information
Henry Beecher M.D. described 23 examples of objectionable research in a 1966 article published in the venerable New England Journal of Medicine. He focused attention on apparent widespread failure to protect the rights and welfare of research subjects.
Beecher HK. Ethics and clinical research. N Engl J Med. 1966;274(24):1354-1360. Available from http://www.hhs.gov/ohrp/documents/BeecherArticle.pdf. Accessibility verified 2006-05-01.
McGee G, Caplan AL. Bioethics For Beginners. Available from http://www.bioethics.net/articles.php?viewCat=3. Accessibility verified 2006-04-27. (Courtesy of The American Journal of Bioethics and Bioethics.net.)
The James Lind Library Collected Articles (short articles explaining the nuts and bolts of research). Accessed on 2007-02-21 at: http://www.jameslindlibrary.org/contents.php
Human Research Collected Articles. Available from http://www.bioethics.net/topics.php?catId=12. Accessibility verified 2006-04-27. (Courtesy of The American Journal of Bioethics and Bioethics.net.)
Wertz DC. Ethics: What Is It and Why Is It Important? A Primer For Non-Ethicists. Undated. Available from http://www.umassmed.edu/shriver/research/socialscience/staff/wertz/ethics.cfm. Accessibility verified 2006-04-27.
Research Initiatives Requiring Institutional and/or Federal Review & Approval: Human Subjects. Undated. Available from http://www.msu.edu/%7Ebiomed/rcr/humsubjects.htm. Accessibility verified 2006-04-27. (Excellent short history of human subject protections from Michigan State University.)
Suellentrop C. What Are the Rules for Experimenting on Humans? Slate Online. 2001-07-21. Available fromhttp://www.slate.com/id/1008035/
National Reference Center for Bioethics Literature Scope Notes Series. Available from http://www.georgetown.edu/research/nrcbl/publications/scopenotes/. Accessibility verified 2006-04-27. (Summary and overview with bibliography on specific issues in biomedical ethics. Scope Note 24 on Gene Therapy is excellent.)
Selected Topics
Mayer M. When Clinical Trials Are Compromised: A Perspective from a Patient Advocate. PLoSMed 2005;2(11):e358. Available from http://medicine.plosjournals.org/archive/1549-1676/2/11/pdf/10.1371_journal.pmed.0020358-S.pdf. Accessibility verified 2006-04-27.
Goldstein M. Evaluating the Usefulness of an 'Innovative' Clinical Procedure: How Can We Really Know If It Works? Research Fact Sheets — Diagnosis / Treatment. United Cerebral Palsy Research and Educational Foundation. August, 1998. Available from http://www.ucp.org/ucp_generaldoc.cfm/1/4/24/24-6608/86. Accessibility verified 2006-04-27.
Richards EP. Introduction to Informed Consent in Torts and Medical Research. Undated. Available from http://biotech.law.lsu.edu/Courses/drugsf02/Introduction_to_Informed_Consent.htm. (Courtesy of the Medical and Public Health Law Site, created and maintained by Professor Edward P. Richards, J.D., M.P.H., Paul M. Hebert Law Center, Louisiana State University at http://biotech.law.lsu.edu/index.htm.) Accessibility verified 2005-09-19.
Anderson AO. Human Subjects Protection at Detrick: Biowarfare to Biodefense Relationship To Evolution of Regulation by Federal Agencies and Oversight Commissions. Accessed on 2010-03-03 at: http://artandersonmd.com/BioDefense/Regs.ppsx
U.S. Federal Agencies
Bren L. Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History. FDA Consumer. March / April 2001. Available from http://www.fda.gov/fdac/features/2001/201_kelsey.html
Lisook AB. The History of FDA's Bioresearch Monitoring Program. 15th Annual Meeting of Associates of Clinical Pharmacology. San Diego, CA. 1991-04-29. Available from http://www.fda.gov/cder/Offices/DSI/Lisook.pdf
Taste of Raspberries, Taste of Death: The 1937 Elixir Sulfanilamide Incident. FDA Consumer. June, 1981. Available from http://www.fda.gov/oc/history/elixir.html
The Long Struggle For The 1906 Law. FDA Consumer. June, 1981. Available from http://www.cfsan.fda.gov/~lrd/history2.html
The Story of the Laws Behind the Labels / Part I 1906 Food and Drugs Act. FDA Consumer. June, 1981. Available from http://vm.cfsan.fda.gov/~lrd/history1.html
The Story of the Laws Behind the Labels / Part II: 1938 Federal Food, Drug, and Cosmetic Act. FDA Consumer. June, 1981. Available from http://www.cfsan.fda.gov/~lrd/histor1a.html
The Story of the Laws Behind the Labels / Part III: 1962 Drug Amendments. FDA Consumer. June, 1981. Available from http://www.cfsan.fda.gov/~lrd/histor1b.html
Hamilton D. A Brief History of the Center for Drug Evaluation and Research. FDA History Office. November, 1997. Available from http://www.fda.gov/cder/about/history/Histext.htm
Swann JP. History of the FDA. in: George Kurian, ed., The Historical Guide to American Government (New York: Oxford University Press, 1998). Available from http://www.fda.gov/oc/history/historyoffda/fulltext.html
Index of FDA History Publications. Available from http://www.fda.gov/oc/history/historypubs.html
FDA Oral History Project. Available from http://www.fda.gov/oc/history/oralhistories/default.htm
A Guide to Resources on the History of the Food and Drug Administration. Available from http://www.fda.gov/oc/history/resourceguide/default.htm
Selected Sources on the History of FDA. Available from http://www.fda.gov/opacom/morechoices/sources.html
Harden VA. A Short History of the National Institutes of Health. National Institutes of Health, Office of NIH history web site. Undated. Available at: http://history.nih.gov/exhibits/history/index.html. Accessibility verified 2006-04-27.
Will I be able to read and understand the definitions? The resources are followed by some key words to help readers.
A rough history of problems in federally-sponsored research leading to government intervention:
Exhibit 3.1: OPRR Compliance Oversight Investigations Resulting in Restrictions/Actions to MPAs, January 1990-June 2000. Chapter 3: Methods for Ensuring Protection: Education, Certification, and Accreditation. In: Ethical and Policy Issues in Research Involving Human Participants, Volume I Report and Recommendations of the National Bioethics Advisory Commission. Bethesda, Maryland August, 2001. p. 54-56. Available from http://www.georgetown.edu/research/nrcbl/nbac/human/overvol1.html. Accessibility verified 2006-03-04.
Year Institution and Action by OPRR
1990
1991
Massachusetts Eye and Ear Infirmary. Certain research was excluded under the existing MPA pending negotiation of a renewed MPA. New participant accruals were suspended pending re-review by appropriately convened IRB and notification of former participants about inadequate informed consent.
NIH. Certain collaborative research was excluded under the existing MPA. Designation of a signatory official with authority to ensure institutional human participant protections, modification of institutional policies and procedures to ensure IRB review of all human participant research, and development of an education program were required.
University of California-San Francisco. New participant accruals in all pediatric oncology research were suspended pending modification of informed consent documents and revised consent for all current pediatric oncology participants, and mechanisms to ensure regulatory compliance in such research were required.
State University of New York College of Optometry. Use of expedited IRB review procedures was suspended. Suspension of human participant involvement in certain research, re-review of research by an appropriately convened IRB, modification of IRB review and record keeping procedures, and designation of a signatory official with authority to ensure institutional human participant protections were required.
Florida State University. Use of expedited IRB review procedures was suspended. Re-review of research by an appropriately convened IRB, modification of IRB review, and record keeping procedures were required.
1992
1993 NIH. Progress reports on implementation of education program were required.
1994
University of California-Los Angeles. Schizophrenia research was excluded under the existing MPA. Modification of informed consent documents, information materials, and record keeping for schizophrenia research, the addition of participant representatives to the IRB, and the establishment of a Data and Safety Monitoring Board for psychiatric disorders research were required.
West Virginia University. Special monitoring of urology department research and modification of IRB review and record keeping procedures were required.
Memorial-Sloan Kettering Cancer Center. Special monitoring of melanoma immunization research, modification of IRB review and record keeping procedures, verification of completeness of informed consent documents, development of handbook of guidelines for investigators, and designation of a signatory official with authority to ensure institutional human participant protections were required.
Medical University of South Carolina. Review of research by appropriately convened IRB, modification of institutional mechanisms to ensure IRB review of human participant research, and development of an education program were required.
University of California-San Diego. Human participant involvement in certain research was suspended, and re-review of research by an appropriately convened IRB, modification of IRB review and record keeping procedures, and designation of a signatory official with authority to ensure institutional human participant protections were required.
University of Florida. Use of expedited IRB review procedures was suspended. Re-review of research by an appropriately convened IRB, modification of IRB review and record keeping procedures, and revision of IRB guidelines for investigators were required.
University of Minnesota. Research conducted by the Department of Surgery was excluded under the existing MPA, and human participant involvement in certain research was suspended. Re-review of research by an appropriately convened IRB, modification of IRB review, and record keeping procedures were required.
1995
University of Virginia. Behavioral and educational research were excluded under the existing MPA, and human participant involvement in behavioral and educational research and certain medical sciences research was suspended. Re-review of research by appropriately convened IRBs, modification of IRB review and record keeping procedures, provision of an enhanced educational program and materials, review of staff support and resources for IRBs, designation of a signatory official with authority to ensure institutional human participant protections, and comprehensive review of IRB policies and procedures were required.
Centers for Disease Control and Prevention. Provision of updated information to measles research participants, development of conflict of interest guidelines for IRB members, review of staff support and resources for IRBs, development of an educational program, a proposal for a mechanism to ensure performance site assurances for international research, and a comprehensive review of IRB policies and procedures were required.
University of California-Los Angeles. Development of an educational program, revised IRB guidelines for investigators and the procedures manual, review of staff support and resources for IRBs, provision of a locked filing system and computerized tracking system to ensure confidentiality of IRB records, and development of mechanisms to ensure that all human participant research receives IRB review were required.
Center for Molecular Medicine and Immunology. Modification of IRB review and record keeping procedures were required.
Veterans Affairs Medical Center, West Los Angeles. Modification of IRB review and record keeping procedures were required.
Cook County Hospital Hektoen Institute for Medical Research. Participant enrollment in research not receiving valid initial or continuing IRB review and use of expedited review procedures were suspended. Revision of IRB review procedures was required.
Cornell University Medical Center. Enrollment in research not receiving adequate initial or continuing IRB review was suspended. Modification of IRB review and record keeping procedures, a plan for increased staffing, a plan for education of IRB members and investigators, and a mechanism for investigation of non-compliance were required.
University of Rochester. Enrollment in research not receiving appropriate initial or continuing IRB was suspended. Review and development of written operating procedures and an investigator handbook, a finalized organization structure of institutional human participant protections, and development of an education program for IRB members and investigators were required.
Wayne State University. Enrollment in research not receiving appropriate initial or continuing IRB review was suspended. Increased staffing and resources for the IRB, development of a mechanism for prompt review of adverse event reports, development of an educational program for IRB members and investigators, and review and revision of IRB policies and procedures were required.
City University of New York. Development of an educational program for IRB members and investigators, review and revision of IRB policies and procedures, revision of sample informed consent documents to comply with DHHS regulations, and revision of IRB record keeping procedures were required.
University of Maryland-Baltimore. Enrollment of participants in research not receiving appropriate initial or continuing IRB review was suspended. Review and revision of informed consent documents for psychiatric research to ensure compliance with DHHS regulations, development of an educational program for IRB members and investigators, and revision of IRB review procedures, including procedures for research involving vulnerable participant populations, were required.
University of California-Irvine. Modification of initial review process to ensure compliance with regulations, revision of continuing review and oversight procedures, increased documentation of IRB actions in accordance with regulations, enhanced education for investigators, IRB members, and staff, and increased support for social and behavioral sciences IRB were required.
Western Carolina Center. Due to limited DHHS support to the Western Carolina Center, Single Project Assurances (SPAs) were required for DHHS-supported human participant research, and the MPA was deactivated on October 30, 1998.
1996
1997
1998
Rush Presbyterian St. Lukes Medical Center. OPRR suspended the MPA for five days pending development of adequate corrective action plans. The MPA was subsequently reinstated with restrictions. OPRR required correction of 17 identified deficiencies in systemic human participant protections, restructuring of systemic human participant protections including changes in leadership, enhanced institutional commitment, and expanded IRB membership, development of an education program for IRB members, IRB staff, and research investigators, suspension of new enrollments in all federally supported research pending review of all such protocols by the reconstituted, convened IRB, and suspension of IRB review of federally supported research by expedited review procedures.
Scripps Clinic and Research Foundation:The Scripps Research Institute. OPRR required correction of 20 identified deficiencies in systemic human participant protections, re-review of all DHHS-supported human participant protocols to include review of complete grant application, development of an educational program for IRB members, IRB staff, and research investigators, and quarterly progress reports.
Duke University. OPRR restricted the MPA and required several corrective actions.
Duke University Medical Center. OPRR restricted the Duke University Medical Center MPA and required several corrective actions.
1999
Friends Research Institute. OPRR removed from coverage under the existing MPA any performance sites outside the Maryland area, removed recognition of one IRB under the MPA, and withdrew approval of all inter-institutional and cooperative amendments to the MPA.
Mt. Sinai School Of Medicine. OPRR restricted the MPA and required satisfactory implementation of a series of corrective action plans.
Veterans Affairs, Greater Los Angeles Health Care System (Formerly Veterans Affairs Medical Center,West Los Angeles). OPRR deactivated the MPA on March 22, 1999. Enrollment of new participants in all federally supported research was suspended, and involvement of previously enrolled participants was allowed only when it was in the best interest of the participant.
Fordham University. Due to the limited number of DHHS-supported projects at Fordham University and persistent concerns about compliance with human participant protections requirements, SPAs were required for all DHHS-supported human participant research, and the MPA was deactivated on May 31, 1999. Duke University Medical Center. OPRR suspended the MPA for five days. OPRR reinstated the Duke University Medical Center MPA with restrictions and required several corrective actions, including re-review of DHHS-supported research by the IRB, implementation of a second IRB, and implementation of appropriate education programs for IRB members, IRB staff, and all investigators.
University of Illinois at Chicago. OPRR restricted the MPA and required corrective actions in response to 29 identified deficiencies, including revision of the MPA to indicate enhanced institutional commitment to the protection of human participants and development of an educational program for IRB members, IRB staff, and research investigators. New enrollments in all federally supported research pending re-review of all such protocols were suspended.
St. Jude Children's Research Hospital. OPRR restricted the MPA and required submission of a progress report describing implementation of all corrective actions three months after the site visit.
Virginia Commonwealth University. OPRR restricted the MPA and required corrective actions, including development of an educational program for IRB members, IRB staff, and research investigators and submission of a list of all active IRB-approved protocols. New participant enrollments in all federally supported research pending re-review of all such protocols were suspended.
Virginia Commonwealth University. OPRR suspended the MPA and required revised corrective action plans, including designation of a new signatory official and new IRB chairpersons.
University of Alabama at Birmingham. OPRR restricted the MPA and required suspension of new participant enrollments in all federally supported research that had not had appropriate initial or continuing review. Submission of corrective action plans to address all deficiencies and concerns related to systemic human participant protections and submission of an educational plan for all IRB members, all IRB staff, and all research investigators were required.
2000
Adapted from Compliance Oversight Investigations Resulting in Restrictions/Actions to Multiple Project Assurances, 1/90-11/99 (OPRR 2000).
U.S. Halts Human Research at Duke. Rick Weiss. The Washington Post. 1999-05-12. Available from http://www.washingtonpost.com/wp-srv/national/daily/may99/duke12.htm
Duke Medical Center Acts to Strengthen Procedures for Human Subject Studies. Duke University Press Release. 1999-05-11. Available from http://web.archive.org/web/19990911001320/http://news.mc.duke.edu/infomatters/News/News.taf?_f=detail&key=2384&site=DUMCNEWS
Studies elsewhere found sloppy in ethics standards and consent. Anne Michaud. The Cincinnati Enquirer. 1999-05-17. Available from http://www.enquirer.com/editions/1999/05/17/loc_studies_elsewhere.html
UC called leader for ending controversial research. Tim Bonfield and Anne Michaud. The Cincinnati Enquirer. 1999-05-17. Available from http://www.enquirer.com/editions/1999/05/17/loc_uc_called_leader_for.html
Last Updated: 2010-03-03
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