April 2004 Bulletin

Human subject research and ethics

Institutional Review Boards and informed consent are vital

By Alan L. Jones, MD

Scientific observation and experimentation for medical progress is conducted at many levels, from basic research through animal models and ultimately to human subjects. Bench medical research can provide new directions and therapies, but the efficacy of these therapies must ultimately be proven in the living human model. Without human subject research, many of today's clinical advances—and those currently being investigated for future application—would not be possible.

Medical investigators are ultimately responsible for the safety of the human volunteers in their programs. Over the past 50 years, the basic tenets of the ethical use of living human subjects have not changed. However, institutional, federal and public oversight has evolved significantly. Consider, for example, the recent development of privacy protections under the Health Insurance Portability and Accountability Act (HIPAA).

Unfortunately, expert medical decision making, sound study design and good intentions do not always ensure the protection and safety of human research volunteers. Consequently, the ethical principles governing human research have been formalized on both an international and national basis, and have been made an integral part of the research process through the use of institutional review boards.

International Standards
The World Medical Association's Declaration of Ethical Principles for Medical Research Involving Human Subjects (Helsinki Declaration) is the authoritative international consensus of medical opinion and forms the ethical basis for human research. Among its requirements are the following:

U.S. Guidelines
The National Research Act of 1974 created the concept of Institutional Review Boards (IRB) and required informed subject consent. Five years later, the Belmont Report, prepared by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, outlined three basic principles that must be considered for ethical human subject research:

Federal agencies such as the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) are charged with regulating various aspects of human subject research. The HHS Policy for Protection of Human Research serves as the national standard governing all human subject research in the United States.

Institutional Review Boards
The composition, conduct, responsibilities and obligations of IRB's are defined by federal code. Basically, an IRB is the group or committee that is given the responsibility by an institution to review that institution's research projects involving human subjects.

The primary purpose of the IRB review is to assure the protection of the safety, rights and welfare of the human subjects. They also may evaluate the scientific merit of the study and the adequacy of human subject protections, as well as monitor ongoing research.

Federal regulations define a human subject as a living individual about whom an investigator conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information. Thus, research involving autopsy materials or cadavers is not generally subject to IRB review.

A researcher undertaking a retrospective review of medical records, however, should not assume such research is exempt from IRB review. Exempt status may be granted, and usually is in an expedited manner, but an IRB project submission is required.

In the United States, essentially all research involving interactions with or collection of private data on human subjects, including retrospective reviews, requires review and approval or exemption by an IRB before it can proceed. Three special situations that involve IRB review and approval relate to the establishment of a new “standard of care,” to the use of deception as a method of collecting information, and to the recruitment of patients for research purposes.

Standard of Care — When a new device or technique becomes available, many physicians will adopt it as the new “standard,” treat a consecutive number of patients and collect specific data prospectively, and then compare the data retrospectively to results from using the previous device or technique. This provides a historical control for measuring the efficacy of the new device or technique.

The decision on whether to use the new technique or device should be a collaborative process between patient and physician, involving the patient's informed understanding and consent. The collection of data in a series of patients, however, constitutes a prospective evaluation of the new device or technique. In most circumstances, therefore, such research would require not only the patient's consent but also IRB approval.

Deception — In general, the use of deception in human research is not advised. “Deceptive” research may use questionnaires advertised as collecting information on a specific topic, when in fact they are really looking for unbiased information on a different topic. For example, orthopaedic residents are recruited for a survey on “evaluating techniques for surgical instruction.” However, the real intent of the survey is to measure the degree of faculty supervision of off-hour trauma cases.

If such a study comes to a negative conclusion and can be localized to a specific region or program, the subjects (orthopaedic residents) or their respective training programs may be subject to retribution. To avoid placing subjects at risk, researchers must carefully consider their study design, implementation and presentation/publication. The required IRB review is an excellent way to help ensure ethical study design.

Recruitment — Patients who are recruited for medical research cannot be approached for participation by someone who does not have prior legitimate access to the individual. The initial contact with a potential subject should be by a physician or caregiver with an established medical relationship. Community advertisements requesting volunteers for participation in research may require review and approval by an IRB.

The responsibility to protect human subjects in medical research rests primarily on the investigators, although medical organizations, scientific forums, publishers and institutions all share some responsibility as well. Regulations and regulatory bodies, such as IRBs, can help ensure ethical study design and development, but the informed consent of the patient is also necessary to ethically conduct human subject research. Whether the researcher is using a device in a way approved by FDA or applying it to an off-label usage, informed patient consent always is required.

Alan L. Jones, MD, is associate professor and vice chairman of the department of orthopaedic surgery at the University of Texas Southwestern (UTS) Medical School. He is also a member of the UTS IRB.


IRB Frequently Asked Questions

What constitutes human research?
Is there an interaction or intervention with a living person that would not occur, or would occur in some other fashion, if not for this research? Will identifiable private data or information be obtained for this research in a form associable with the individual? If the answer to either question is yes, you are conducting human research.

Is any research exempt from IRB review?
Research that solely includes existing data or specimens that are publicly available or that will not be recorded in a fashion that can be linked to the subject is exempt. Retrospective reviews of medical records are not automatically exempt and require an IRB project submission.

Are there special concerns for healthy volunteers?
Yes. Because healthy volunteers are unlikely to benefit directly from participation, their safety and rights must be carefully considered. Every effort must be made to minimize risks to subjects. Although one or more of the investigators may participate as a subject, subordinates (employees, residents, students) are not allowed because they may be subject to coercion.

Is IRB approval required for an observational study of an FDA-approved device or drug?
In most cases, yes. Both IRB approval and subject consent are required if you plan to prospectively collect any specific information or perform any additional examinations or imaging studies. IRB approval and subject consent also are required if the information obtained can be linked to a specific subject. Additionally, if the drug or device does not have specific FDA approval for the indication being used in the study, an investigational new drug (IND) or investigational device exemption (IDE) from the FDA is required.

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