Year |
Milestone |
Status |
Description |
Antiquity |
Hippocratic Oath
[See text / Download PDF]
[Compare the current principles of ethics of the American Medical Association ]
[Compare a modernized version of the Oath] |
Code of professional ethics |
Physician has an ethical responsibility to the patient as well as to the medical tradition. |
1938 |
Food and Drug Act
[See web page for current FD&C Act]
|
U.S. Law |
Requires that drugs be shown to be safe before marketing. This leads to the need for human trials. |
1947 |
Nuremberg Code
[See text / Download PDF] |
International code of ethics |
Informed consent required for experiments.
Experiments must be scientifically necessary and conducted by qualified personnel.
Human trials should be preceded by animal studies and surveys of a disease's natural history.
Benefit to science must be weighed against risks and suffering of experimental subjects. |
1949 |
International Code of Medical Ethics of the World Medical Assembly, including the Declaration of Geneva
[See text / Download PDF] |
International code of professional ethics |
A physician shall always bear in mind the obligation of preserving human life.
The health of the patient shall be the physician's first consideration.
A physician shall act only in the patient's interest when providing medical care which might have the effect of weakening the physical and mental condition of the patient. |
1953 |
NIH Clinical Center policy
[See Clinical Center policy web site/
Download PDF of human subject policy]
|
Agency policy |
Ethical responsibility for medical experiments lies with the study's principal investigators. |
1962 |
Kefauver-Harris amendments to the 1938 Food, Drug, and Cosmetic (FD&C) Act
[Public Law 87-781; 76 Stat. 788-89]
[See web page for current FD&C Act]
|
First U.S. law requiring informed consent |
FDA empowered to ban drug experiments in humans pending animal trials for safety. |
1963 |
FDA regulations
[21 CFR 130.3, later incorporated in
45 CFR 46 (see below)] |
U.S. Regulations |
Clinical investigators required to certify informed concent as required by the Kefauver-Harris amendments. |
1964 |
Helsinki Declaration signed by U.S. (revised in 1975, 1983, 1989)
[See text / Download PDF] |
International ethical guidelines |
Clinical research should be based on animal and laboratory experiments.
Clinical research should be conducted and supervised only by qualified medical workers.
Clinical research should be preceded by a careful assessment of risks and benefits to the patient.
Human beings should be fully informed and must freely consent to the research.
Responsibility for the human subject must always rest with a medically qualified person, and never with the subject.
Results of experiments that do not comply with ethical guidelines should not be accepted for publication.
Special care must be taken with informed consent of minors.
Also mentions consideration of the welfare of animal subjects and the environment. |
1966 |
U.S. Surgeon General policy statement
["Clinical research and investigation involving human beings," Surgeon General, Public Health Service to the Heads of the Institutions Conducting Research with Public Health Service Grants] |
U.S. policy |
All human subject research requires independent prior review. Origin of Institutional Review Boards (IRBs). |
1966 |
FDA regulations
[21 CFR 130.37, later incorporated in
45 CFR 46 (see below)] |
U.S. Regulations |
Specific requirements of informed consent defined. |
1974 |
National Research Act
[Title II, Public Law 93-348]
[See web page for current U.S. Code on Public Health Service research and investigations]
|
U.S. Law |
Regulations to be codified.
All research funded by DHEW to be reviewed by IRBs. |
1974 |
Regulations for the Protection of Human Subjects of Biomedical and Behavioral Research
[45 CFR 46]
[See text / Download PDF]
|
U.S. Regulations |
IRB procedures established. |
1974 |
45 CFR 46 Subpart B
[see current 45 CFR 46 above] |
U.S. Regulations |
Special protections for pregnant women and fetuses. |
1978 |
45 CFR 46 Subpart C
[see current 45 CFR 46 above] |
U.S. Regulations |
Special protections for prisoners. |
1979 |
Belmont Report (Report on Ethical Principles and Guidelines for the Protection of Human Subjects of Research), issued by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission)
[See text / Download PDF] |
U.S. ethical guidelines |
Principal of Respect: recognizes the autonomy of humans and requires clear informed consent.
Principal of Beneficence: Research must be shown to be beneficial and reflect the Hippocratic idea of do no harm.
Principle of Justice: The benefits to some must be balanced against the risks to subjects. |
1980-1983 |
President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (President's Commission) |
Recommendations became basis of 10 CFR 745 ("Common Rule", below) |
Recommended that all federal agencies adopt the human subject regulations of the Department of Health and Human Services (DHHS, formerly DHEW). |
1981 |
FDA regulations revised.
Informed consent [21 CFR 50]
[See text / Download PDF]
IRBs [21 CFR 56]
[See text / Download PDF] |
U.S. Regulations |
Revised to correspond to DHHS regulations. |
1983 |
45 CFR 46 Subpart D
[see current 45 CFR 46 above] |
U.S. Regulations |
Special protections for children. |
1991 |
Common Federal Policy for the Protection of Human Subjects ("Common Rule")
[10 CFR 745]
[See text / Download PDF] |
U.S. Regulations |
Sixteen agencies adopt the regulations of 45 CFR 46 subpart A.
Subparts B, C, D adopted by many agencies. |
1995 |
Final report of Advisory Committee on Human Radiation Experiments (created in 1994)
[See report website] |
Report |
Further means required to ensure highest ethical standards.
Special care to be taken where research must be kept secret. |
1995-2001 |
National Bioethics Advisory Commission (NBAC)
[Download list of publications PDF] |
Series of ethical and policy reports |
|
1996 |
FDA regulations revised.
[21 CFR 50.24]
[See text / Download PDF] |
U.S. Regulations |
Allows exception from informed consent requirements for research studies involving emergency research. |
1996 |
International Conference on Harmonisation, Guideline E6: Good Clinical Practice, Consolidated Guideline
[Download PDF] |
International guidelines |
Good clinical practice as an inernational standard that provides public assurance that trial subjects are protected. U.S., E.U, Japan are all signatories. |
2000 |
World Health Organization Operational guidelines for ethics committees that review biomedical research
[View webpage / Download PDF] |
International guidelines |
Intended to facilitate and support ethical review in all countries around the world. Suggests role, constituents and requirements for ethics committees. |
2001 |
Best Pharmaceuticals for Children Act
[View web page / Download PDF] |
U.S. Law |
Provides six-month patent extension for manufacturers who conduct voluntary pediatric trials. |
2002 |
Suspension of rule requiring pediatric studies of medicines for children.
[View Washington Post article] |
FDA rule |
Two-year suspension of 1997 rule. Safety concerns considered addressed by incentive under Best Pharmaceutical for Children Act, above. |
2002 |
Products to Treat Exposure to Toxic Substances may be Approved Without Human Testing
[View FDA news release /
Download PDF of final rule (3.3 MB)] |
U.S. Regulations |
FDA Regulations amended to allow animal-based approval of treatments for toxic exposure when human efficacy studies are not ethical or feasible. Part of emergency response effort. |