Human Subjects: What research participants should know !

Humans are an important part of testing new ideas, new products, and new techniques. All of these advances in science and make life better, safer, healthier and more productive for everyone. Humans, however, can be vulnerable in this process. Jargon, sophisticated language, and complex or scientific concepts can make people who like to help advance research feel at a disadvantage. In the unfamiliar world of research it is easy to feel confused or fearful about asking questions or saying, "I still don't exactly understand." Other individuals may have serious health worries or be afraid due to life threatening diagnoses. Because of these circumstances might be willing to agree to participate in a study without giving fully informed consent to the requirements of the study.

The Federal Government heavily regulates all universities and scientific organizations that are involved with the administration or coordination of research activities. The Department of Health and Human Services (DHHS), i.e., the Federal Policy, and the regulations of the Food and Drug Administration (FDA), is the agency that has this mandate. In a place like a University there is a campus organization that is responsible for implementing, regulating and policing this effort. They are usually called an Institutional Review Board (IRB). This is the administrative body established to protect the rights and welfare of human subjects (including patients) who are recruited to participate in research activities. The IRB has the authority to approve, require modifications in, or disapprove all research activities involving humans that fall within its jurisdiction. The jurisdiction of a University IRB is defined by its binding commitment (Assurance # M-1259) with the DHHS.

All of the regulations to protect human subject proceed from this commitment. These regulations specifically discuss which institutions, locations, funding streams, and personnel are under the regulation of the regulating IRB. The regulation in this commitment must be carefully and rigorously followed. Universities and research organizations are in jeopardy of loosing ALL of their Federal research funds if the IRB is found to be lax or careless in regulating even just one research study. The press has publicized recent problems at major universities that brought potential financial ruin due to careless attitudes toward caring for the protection of human subjects.

There is a specific unit within the DHHS called the Office for Protection from Research Risks (OPRR) that implements and oversees IRB compliance. (This agency has a website that makes it very easy to learn more about this topic.) ( It checks for compliance with the Federal Policy and provides instruction and guidance on ethical issues related to human subject research. A University's Research Conduct and Compliance Office is responsible for establishing and administering institutional policies and procedures through which their University conforms to both the Federal Policy and the FDA regulations that govern the protection of human subjects participating in research (human research subjects).

The purpose of a University IRB is to assure both in advance and by periodic monitoring, that appropriate steps are being taken to protect the rights and welfare of human research subjects. (For an example of a University IRB website and the resources it may include take a look at the University of Pittsburgh's IRB.) To accomplish this purpose, the IRB uses a group deliberation process to review and approve research protocols and related materials (e.g., informed consent documents, investigator brochures).

The focus of the process is to ensure that:

1. the risks to human research subjects are minimized by using procedures that are consistent with sound research design and that do not unnecessarily expose the research participants to risk, and whenever appropriate, by using procedures already being performed on subjects for diagnosis or treatment purposes.
2. the risks to human research subjects are reasonable in relation to the anticipated benefits (if any) to the individual, and the importance of the knowledge that may be expected to result. For the purpose of IRB consideration, "benefit" is defined as a valued or desired outcome; an advantage. For the purpose of IRB consideration, "risk" is defined as the probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. In evaluating risk, the IRB is to consider the conditions that make the situation dangerous, per se (i.e., as opposed to those chances that specific individuals are willing to undertake for some desired goals). In evaluating risks and benefits, the IRB considers only those risks and benefits that may result from the research (i.e., as distinguished from risks and benefits of treatments or procedures that the patient would undergo if not participating in the research). In evaluating risks and benefits, the IRB does not consider possible long-range effects of applying knowledge gained in the research (e.g., the possible effects of research on public policy).
3. the selection of human subjects or patients for research participation is equitable.
4. human research subjects are adequately informed of the risks and benefits of research participation and the procedures that will be involved in the research; and that informed consent is obtained from each prospective human research subject, or his/her legally authorized representative, in accordance with, and to the extent required by federal regulations and IRB policies.
5. informed consent of human research subjects is obtained in advance of research participation and appropriately documented in accordance with, and to the extent required by federal regulations and IRB policies.
6. the research plan, when appropriate, makes adequate provision for monitoring the data collected to ensure the safety of human research subjects.
7. there are adequate provisions to protect the privacy of human research subjects and to maintain the confidentiality of research data.
8. appropriate additional safeguards have been included in the study to protect the rights and welfare of human research subjects who are likely to be vulnerable to coercion or undue influence (e.g., children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons).

Definition of Research

The other issue that arises is what exactly is research. The University Institutional Review Board (IRB) is required to review and approve all research activities involving human subjects prior to their implementation. There is sometimes a question of whether a planned activity is "research" and, therefore, requires IRB review and approval. The DHHS Federal Policy defines research as "a systematic investigation, including research development, testing and evaluation, designed to develop or to contribute to generalizable knowledge." Specific criteria that can be used to determine whether a planned activity is research include:

1. the testing of a hypothesis or question for which an answer requires more information.
   the prospective or retrospective collection of data from human subjects/patients with the intent to publish such results.
2. he use of a standard procedure or an approved drug if its use is influenced by any consideration other than the direct welfare of the individual. For example: a selection between different, although widely-accepted, procedures or therapies according to a predetermined plan such as randomization; or the administration of a standard procedure or an approved drug to a healthy "control" subject.
3. the use of an experimental (investigational) drug, biologic or device (e.g., a drug that is the subject of a FDA-approved investigational new drug (IND) exemption or a device that is not FDA approved).

Innovative or newly introduced clinical procedures or therapies do not require IRB review and approval except when they involve "research" as defined by the above criteria. (An innovative clinical practice is an intervention designed solely to enhance the well being of an individual patient or client. The purpose of an innovative clinical practice is to provide diagnosis, preventative treatment, or therapy to particular individuals.) It is recommended that the introduction of innovative procedures or therapies into clinical practice (i.e., independent of a research activity approved by the IRB) be reviewed with the applicable department chairperson and the Office of Risk Management prior to their implementation.

Scientific Review Committees

Even before a research study goes to the IRB for approval, the research protocols (including the informed consent document(s)) must be reviewed by an appropriate and formally constituted scientific review committee. This process assures the IRB that the specific aims and/or design of the research protocol are sound. Scientific committee review of the research protocol addresses such issues as scientific merit; research subject availability; resource utilization; compliance with applicable federal, state, and University policies; and readability and submission format. Submission of the research protocol (or substantial modifications to the protocol) to the IRB shall be accompanied by a letter or other notification (i.e., signed by the chairperson of the scientific review committee or if no scientific review committee is established, the responsible administrator of the department, school, or multidisciplinary center/institute to whom the principal investigator reports) indicating that the scientific review committee found the research protocol and consent form(s) acceptable for IRB submission.

All IRB-approved research protocols must be submitted annually (or sometimes more frequently) for renewal approval. If substantial changes have been made in the course of the time period, then evidence that a scientific committee has reviewed the proposal and approved the changes must accompany the annual renewal.

Conclusion

The bottom line for research study participants is that the IRB by which is regulating and approving the research study you are involved in has your best interest at heart. It is required that a consent form offer you the phone number and contact information so you can easily and confidentially reach the specific IRB office. Don't be afraid to ask questions or to questions unresolved issues. People who act as research study participants deserve to be treated fairly and carefully and with respect for the contribution that they are making to science.

Written by:
Mary Ellen Buning, MS, OTR/L, ATP with materials taken from the Manual of the Institutional Review Board of the University of Pittsburgh, Pittsburgh, PA, 15260.

Last Updated: 3-2-2006