In the second part of the clinical trials series, we examine the duties and obligations of Sponsors and Clinical Research Organizations (CRO) as it relates to the protection of human subjects who participate in clinical trials. Generally, a “Human Subject” is an individual who is (or becomes) a participant in research, either as a recipient of the test article or as a control group participant. A subject may be either a healthy human or a patient. See 21 CFR 50.3 An Institutional review board (IRB) means any board, committee, or other group formally designated by an institution to review biomedical research involving humans as subjects, to approve the initiation of and conduct periodic review of such research. As set forth in 21 CFR 56.106, IRBs are required to register with the Department of Health and Human Services.

The primary responsibility of an IRB is to ensure that human subjects are protected, and appropriate disclosures are provided to human subjects. Among other duties, the IRB has the is responsible for the review and approval of the clinical trial design, protocol or methodology. Moreover, the IRB oversees the selection of human subjects, whether the informed consent provided is appropriate, the qualifications of investigators and whether there is proper balance of the risks and benefits to human subjects. The IRB should be comprised of at least five (5) members with diverse backgrounds with respect to education, training and experience. While scientific training and knowledge is necessary, IRB’s should not be homogenous as to profession. Particularly, IRB’s should have a scientist member and a nonscientist member as well. Moreover, IRBs should strive to be diverse with respect to race, religion, culture background, gender, sexual orientation amount other factors. IRB candidates should be free from conflicts of interest (whether financial or otherwise) and should be vigorously screened to ensure that they are not affiliated (directly or indirectly) with the sponsor.

Once the IRB is assembled, some established written procedures are critical and should be subject to ongoing review. Most critically, an IRB should have the authority to review and approve any changes in research protocols. And the IRB should have protocols in place which streamline reporting to the appropriate officials and/or the FDA as to i. any unanticipated problems involving risks to human participants; ii. Any instance of serious or continuing noncompliance with the CFR(s) and iii. Any suspension or termination of IRB approval(s).

IRB approval of research is subject to the requirements of 21 CFR 56.111, which states in part:

“(a) In order to approve research covered by these regulations the IRB shall determine that all of the following requirements are satisfied:

(1) Risks to subjects are minimized:

(i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and

(ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies that subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

(3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons.

(4) Informed consent will be sought from each prospective subject or the subject’s legally authorized representative, in accordance with and to the extent required by part 50.

(5) Informed consent will be appropriately documented, in accordance with and to the extent required by § 50.27.

(6) Where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

(7) Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

(b) When some or all of the subjects, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons, are likely to be vulnerable to coercion or undue influence additional safeguards have been included in the study to protect the rights and welfare of these subjects.”

While we will address informed consent component in the next publication, understanding the role of the critical IRB and its importance in clinical research is both legally mandated and essential to ensure that appropriate safeguards to protect patients in the clinical setting.