Regulatory Considerations in Human Subjects Research

 1. The voluntary consent of the human subject is absolutely essential. The person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him/her to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonable to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.

 2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.

 3. The experiment should be so designed and based on the results of animal experimentation and knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.

 4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

 5. No experiment should be conducted where there is a prior reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.

 6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.

 7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.

 8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.

 9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible.

10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

Subsequently, in the 1960s the Declaration of Helsinki was developed by the World Medical Association as a set of ethical principles regarding human experimentation for the medical community. It is widely regarded as the cornerstone document of human research ethics. It is not a legally binding instrument, but has been used as the basis for legal statues and regulations overseeing human subjects research in numerous countries including the United States. The Declaration was originally adopted in June 1964 in Helsinki, Finland, and has since undergone multiple revisions.

Prior to the 1947 Nuremberg Code there were no broadly established principles that addressed the ethical aspects of human research. The Helsinki Declaration was based on the principles first stated in the Nuremberg Code, with some modifications. For example, the Declaration promoted a broader definition of the need for informed consent from “absolutely essential” under Nuremberg to “if at all possible”; research was allowed without consent where a proxy consent, such as a legal guardian, was available.

8.2.2 The Belmont Report

As a result of the Tuskegee Study and influenced by the tenants of the Helsinki Declaration, the National Research Act was signed into law by Congress on July 12, 1974. The Act authorized the creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. One of the charges to the Commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines that should be followed to assure that such research is conducted in accordance with those principles. The final report was issued in 1978 and was entitled The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It is commonly referred to as “the Belmont Report” and takes its name from the Belmont Conference Center in Elkridge, Maryland, where it was drafted (www.​wikipedia.​org/​wiki/​Belmont_​Report, retrieved 12-29-2012). The Belmont Report defines three principles described in Table 8.2 (http://​ohsr.​od.​nih.​gov/​guidelines/​belmont.​html).

Table 8.2
Principles of the Belmont Report

1. Respect for persons: Protecting the autonomy of all people (research subjects), treating them with courtesy and respect, and providing informed consent. Researchers must be truthful and conduct no deception

2. Beneficence: The philosophy of “do no harm” while maximizing benefits for the research project and minimizing risks to the research subjects

3. Justice: Ensuring reasonable, nonexploitative, and well-considered procedures are administered fairly—the fair distribution of costs and benefits to potential research participants—and equally

8.3 Regulation of Human Subjects Research

8.3.1 The Code of Federal Regulations and Federalwide Assurance for the Protection of Human Subjects

In 1991, 14 federal departments and agencies joined HHS in adopting a uniform set of regulations for the protection of human subjects, identical to subpart A of 45 CFR part 46 of the HHS regulations. This uniform set of statutes constitutes the Federal Policy for the Protection of Human Subjects, informally known as the “Common Rule.” The Office for Human Research Protections (OHRP) was also established under the Assistant Secretary for Health in the Department of HHS; it is responsible for the protection of the rights, welfare, and well-being of research subjects in research conducted or supported by the US Department of Health and Human Services (www.​hhs.​gov/​ohrp/​about/​index.​html). The OHRP principally interacts with biomedical research institutions to ensure compliance with HHS regulations as described in Title 45, Part 46, Code of Federal Regulations (45 CFR 46). The Division of Education and Development provides guidance to individuals and institutions conducting HHS-supported human subjects research. The Division of Policy and Assurances administers the Federalwide Assurance (FWA) of compliance and registration of institutional review boards.

The FWA is applicable to any institution that is engaged in human subjects research that is conducted or supported by any US federal department or agency that has adopted the Common Rule. The institution must renew its FWA every 5 years, even if no changes have occurred, in order to maintain an active FWA. There are rare circumstances under which human subjects research is exempt from the Common Rule but almost all research conducted at academic biomedical research institutions is covered under the FWA. The FWA number may be needed for grant applications that involve human subjects research, and the number should be available to an individual researcher from the institutional Human Research Protection Office (HRPO). A description of the elements of an FWA is listed at www.​hhs.​gov/​ohrp/​assurances/​assurances/​filasurt.​html. The FWA includes a statement from the institution that all human subjects research will be conducted ethically and that the rights and welfare of human research subjects will be protected. The principles are generally adopted from the Declaration of Helsinki and the Belmont Report. The institution must provide a description of procedures to ensure prompt reporting of any deviations of principles and policies to the institutional review board, the US federal department or agency conducting or supporting the research and OHRP.

8.3.2 Institutional Review Boards

Under the FWA, an institution must constitute an Institutional Review Board (IRB) to review, approve, and provide oversight of human subjects research. The institution may be required to provide its written procedures regarding human subjects research to the OHRP or any US federal department or agency conducting or supporting research to which the FWA applies. Based on the 45 CFR 46, an IRB is required to (1) conduct initial and continuing annual reviews of research and report its findings to the investigator and the institution, (2) determine which projects require review more often than annually and which need verification from sources other than the investigator that no material changes have occurred since the previous IRB review, (3) ensure prompt reporting to the IRB of proposed changes to any research activity, and (4) ensure that proposed changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval (except when necessary to eliminate apparent immediate hazards to the subjects). The last point is important in that it means that any investigator may deviate from the approved research plan if, in his or her judgment, that deviation is essential to reduce an immediate risk to the subject.

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Sep 26, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Regulatory Considerations in Human Subjects Research

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