1. History and Ethical Principles
Jeffrey M. Cohen, Ph.D. Director, Division of Education Office for Human Research Protections

2. Pre WWII Edward Jenner (1789) Smallpox Vaccine
Claude Bernard (1865) Ethical Maxims
Louis Pasteur (1885) Rabies Vaccine
Walter Reed (1900) Yellow Fever

3. Nuremberg
During the Nuremberg War Crimes Trials, 23 German doctors were charged with crimes against humanity for “performing medical experiments upon concentration camp inmates and other living human subjects, without their consent, in the course of which experiments the defendants committed the murders, brutalities, cruelties, tortures, atrocities, and other inhuman acts.”

4. The Nuremberg Code (1947)
As part of the verdict, the Court enumerated some rules for "Permissible Medical Experiments", now known as the “Nuremberg Code”. These rules include:
voluntary consent
benefits outweigh risks
ability of the subject to terminate participation

5. Declaration of Helsinki
Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects
Adopted by the 18th World Medical Assembly, Helsinki, Finland, and as revised by the World Medical Assembly in Tokyo, Japan in 1975, in Venice, Italy in 1983, and in Hong Kong in 1989 and the 48th General Assembly, Somerset West, Republic of South Africa, October
“Concern for the interests of the subject must always prevail over the interests of science and society.”

6. Post WWII
Willowbrook (1950s) mentally retarded children were deliberately infected with hepatitis virus
Jewish Chronic Disease Hospital (1960s) Live cancer cells were injected into 22 senile patients
Milgram (1963) "Behavioral study of odedience"
Humphries (1970) Tearoom Trade: Impersonal Sex in Public Places

7. Beecher Article
“Ethics and clinical research” Henry K. Beecher New Engl J Med 274 (1966):
22 published medical studies presenting risk to subjects without their knowledge or approval
Published in some of the most prestigious journals and conducted at some of the most prestigious institutions

8. Public Health Service Policy
NIH Director and Surgeon General requested that the National Advisory Health Council review human subject protections
Council recommended prior institutional review for PHS supported research to:
Protect of the rights and welfare of the subjects
Assure appropriate methods of informed consent
Determine acceptable balance of risks and benefits
Adopted as Public Health Service policy in 1966
Beginnings of the Institutional Review Board (IRB)

9. Tuskegee Syphilis Study
American medical research project conducted by the U.S. Public Health Service from 1932 to 1972, examined the natural course of untreated syphilis in black American men. The subjects, all impoverished sharecroppers from Macon county, Alabama, were unknowing participants in the study; they were not told that they had syphilis, nor were they offered effective treatment.

10. National Research Act
1973 Kennedy Hearings “Quality of Health Care - Human Experimentation”
1974 National Research Act
Established the “National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research”
Required IRBs at institutions receiving HEW support for human subjects research

11. The Belmont Report
Ethical Principles and Guidelines for the Protection of Human Subjects of Research
The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
April 18, 1979

12. The Belmont Report Basic Ethical Principles: 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

13. Federal Regulations and Policy
45 CFR 46 - Basic DHHS Policy for Protection of Human Research Subjects Originally adopted May, 1974, Revised January 13, 1981, Revised June 18, 1991
Additional protections for vulnerable populations in Subparts B-D
Federal Policy for the Protection of Human Subjects - “The Common Rule” June 18, 1991
Departments of Agriculture, Energy, Commerce, HUD, Justice, Defense, Education, Veterans Affairs, Transportation, and HHS. NSF, NASA, EPA, AID, Social Security Administration, CIA, and the Consumer Product Safety Commission.

14. Basic Protections
The regulations contain three basic protections for human subjects:
Institutional Assurances
IRB Review
Informed Consent

15. Institutional Responsibilities
Institutions bear full responsibility for all research involving human subjects covered under their Assurance
All requirements of 45 CFR 46 must be met for all federally-sponsored research
OHRP strongly encourages institutions to embrace the HHS regulations regardless of sponsorship, and to commit to this standard in their Assurance.

16. IRB Decision Matrix BENEFICENCE JUSTICE RESPECT FOR PERSONS
Risk/Benefit Analysis
Experimental Design
Qualifications of PI
Subject selection
Inclusion/exclusion
Recruitment
Protection of subjects (especially vulnerable populations)
Informed consent
Surrogate consent
Assent
J. Cooper, Albany Medical Center

17. The Consent Process
Informed consent is not a single event or just a form to be signed -- rather, it is an educational process that takes place between the investigator and the prospective subject.
The basic elements of the consent process include:
full disclosure of the nature of the research and the subject's participation,
adequate comprehension on the part of the potential subjects, and
the subject's voluntary choice to participate.
Adequate Informed Consent. Only the subjects can evaluate the degree of risk in a given situation. The IRB must ensure that subjects are given sufficient information regarding the study to determine for themselves what the risks are and whether they want to assume those risks.
Must be understandable to subjects: Risks described in terms that the subjects can understand. Comparisons to everyday risks.
Avoid Bias and Creation of Negative Mindsets: Consent process should not increase the likelihood of harm.

18. Tampa Tribune 3/11/00
TAMPA - A lawsuit accusing USF doctors of experimenting on pregnant women without their consent is settled for $3.8 million…. The experiment wasn't considered risky and no adverse effects were documented, plaintiffs in the suit agree. However, the failure to inform … as many as 3, pregnant women of various experiments conducted between 1986 and 1990 has cost Tampa General Hospital, USF and the state $3.8 million.

19. Overarching Concerns
Does the institution support and respect the IRB and its mission?
Is there a “culture of compliance”?
Are IRB members and investigators knowledgeable about regulatory requirements?
Is there adequate documentation of IRB findings and actions?