​​Frequently Asked Questions​​​​​​​​​

I. INSTITUTIONAL REVIEW BOARD REGULATIONS

What is an Institutional Review Board (IRB)? 
An IRB is a board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct continuing review of biomedical research involving human subjects in accordance with FDA regulations. An IRB has the authority to approve, require modifications in (to secure approval), or disapprove this research. The purpose of IRB review is to assure that:

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.

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.

Selection of subjects is equitable.

Informed consent will be sought from each prospective subject or the subject's legally authorized representative and will be documented in accordance with, and to the extent required, by FDA's informed consent regulations.

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

There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

Appropriate additional safeguards have been included in the study to protect the rights and welfare of subjects who are members of a particularly vulnerable group.

Do IRBs have to be formally called by that name? 
No, IRB is a generic term used to describe a committee whose function is to review research and to assure the protection of the rights and welfare of the human subjects in accordance with FDA regulations. Each institution may use whatever name it chooses; regardless of the name chosen, the committee is subject to the FDA IRB regulations when the use of FDA regulated products is reviewed and approved.

Whom can an IRB contact to determine whether an investigational new drug application or investigational device exemption (IND or IDE) is required for a study of a drug or device?
For clinical investigations involving a drug, the IRB can contact the Document Management and Reporting Branch, Center for Drug Evaluation and Research (CDER), (301) 443-4320; for a biological product, the Division of Biological Investigational New Drugs, Office of Biologic Research and Review, Center for Biologic Evaluation and Research (CBER), (301) 443-4864; and for a medical device, the Office of Device Evaluation, Center for Devices 'and Radiological Health (CDRH), (301) 427-8162. If the IRB is unsure about whether a test article is a "drug" or a "device," the IRB may contact the Office of Health Affairs, (301) 443-1382.

May a clinical investigator be an IRB member?
Yes. However, the IRB regulations (21 CFR 56.107(e)) prohibit any member from participating in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IR-B.

The IRB regulations require an IRB to have a diverse membership; can one member satisfy more than one membership category? 
Yes. For example, one member could be female, otherwise unaffiliated with the institution, and with a primary concern in a non-scientific area. This individual would satisfy three of the membership requirements of the regulations if there is a male member on the committee.

Must an institution conducting research involving human subjects establish its own IRB? 
No. Although IRBs frequently exist in an institution which conducts research involving human subjects, this is not required by FDA regulations. Generally, however, institutions engaged in research involving human subjects will have their own IRBs to review that research conducted on the premises or elsewhere by the staff of the institution.

Can a hospital IRB review a study that will be conducted outside of the hospital?
Yes. Although a hospital IRB is not required to review studies conducted outside the jurisdiction of its institution, the IRB may choose to do so with the institution's approval.

Can IRB members be paid for their services?
The regulations do not discuss payment of IRB members. There is nothing in FDA regulations to preclude a member from being compensated for review services rendered, for example as a consultation fee. Travel expenses may also be reimbursed.

What is the FDA role in IRB liability in malpractice suits? 
As discussed in the preamble to the FDA IRB regulations (46 FR 8961), FDA regulations do not address the question of IRB or institutional liability in the case of malpractice suits. Moreover, FDA does not have the authority to grant limited liability to IRBs or their members.

What happens during an FDA inspection of an IRB?
FDA field investigators interview institutional officials and examine the IRB's records to determine whether the IRB is in conformance with FDA regulations. See the information sheet entitled: "FDA Institutional Review Board Inspections" for a complete description of the inspectional process.

The FDA IRB regulations exempt emergency use of a test article from prospective IRB review "... provided that such emergency use is reported to the IRB within five working days. Any subsequent use of the test article at the institution is subject to IRB review." (Section 56.104) What does "subsequent use" mean?
Under this provision, in an emergency, that is, in a situation in which use of a test article at an institution was not foreseeable, an investigator may administer the required course of treatment for the investigational drug to one patient without prospective IRB review, provided that use is reported to the IRB within 5 days. Any use of the same drug in another patient in the institution would be considered a "subsequent use" and be subject to prospective IRB review.

An investigational drug may be administered by several investigators in an institution under this emergency use provision, without an individual investigator knowing that the drug had previously been administered in the institution under the emergency use provision. If an IRB, during retrospective review, finds that a given test article is used in justifiable emergency situations by several investigators, or if further justifiable emergency situations are anticipated, the IRB should request that a protocol be developed for prospective IRB review, listing all investigators who may use the article in the institution in the future. By reviewing and approving this protocol prospectively, subsequent use of the test article would not be subject to the emergency use provision for those investigators.

What is expedited review? 
Expedited review is a procedure through which certain kinds of research may be reviewed and approved without convening the full IRB. The FDA IRB regulations (21 CFR 56.110) permit, but do not require, an IRB to review certain categories of research, which appear on a list published in the Federal Register on January 27, 1981 (46 CFR 8980), through an expedited procedure if the research involves no more than minimal risk. The IRB may also use the expedited review procedure to review minor changes in previously approved research during the period covered by the original approval. Under an expedited review procedure, review of research may be carried out by the IRB chairperson or by one or more experienced members of the IRB designated by the chairperson. Reviewers may exercise all the authorities of the IRB except that they may not disapprove the research. Research can only be disapproved following review by the full committee. The IRB is also required to adopt a method of keeping all members advised of research proposals which have been approved through the expedited review procedure.

Section 56.115(a)(1) requires that the IRB maintain copies of "research proposals reviewed." Is the "research proposal" the same as the formal study protocol which the investigator receives from the sponsor of the research? 
Some institutions only require the investigator to submit the formal study protocol for review. Others require the investigator to submit an institutionally-developed form which, when completed, provides the IRB with all of the information it needs to review the study. Still others require some variation or combination of the above. At least one member of the IRB must review the entire protocol. Others may receive a summary form, but the complete protocol must be available to them on request. Regardless of the system used, the IRB must receive sufficient information upon which to base approval/disapproval of the study (see the criteria for IRB approval in 21 CFR 56.111). Copies of all information reviewed are to be maintained for at least three years after completion of the research.


II. INFORMED CONSENT REGULATIONS

Is the purpose of the IRB review and of informed consent to protect the institution or the subject? 
The fundamental purpose of IRB review and of informed consent is to assure that the rights and welfare of subjects are protected. A signed informed consent form is evidence that the information contained in the form has been provided to a prospective subject. IRB review of the form to ensure that the subject is given adequate information concerning the study serves a dual function-protection of the subject and documentation that the institution complied with applicable regulations.

Is getting the subject to sign a consent form all that is required by the informed consent regulations? 
No. The consent form itself is merely an aid to ensuring that adequate information is provided to the subject. The signed consent form provides documentation of a subject's consent to participate in a study. The entire informed consent process involves giving a subject adequate information concerning the study, providing adequate opportunity for the subject to consider all options, responding to the subject's questions, ensuring that the subject has comprehended this information, and, finally, obtaining the subject's voluntary consent to participate. To be effective, the process must provide an opportunity for the investigator and the subject to exchange information and ask questions. The consent form, therefore, is not an end point; it is one step in this communicative process.

Section 50.27(a) of the FDA informed consent regulation requires a copy of the consent form to be given to the person signing the form. Does this copy have to be a Photostat of the form with the subject's signature affixed? 
No. The copy of the form given to the subject need not be a copy of the signed form, but may be a copy of the form given to the subject to sign. The purpose of providing the person signing the form with a copy of the consent form (21 CFR 50.27(a)) and with a copy of the written summary of the information presented in the case of a "short form" (21 CFR 50.27(b)(2)) is to allow the subject continuing access to the information provided.

If an IRB uses a "fill-in-the-blank" consent form, does the IRB need to review the filled out form for each study? 
Yes. A fill-in-the-blank form provides only a format for presenting the relevant study information to the subject. The IRB must review a completed sample form, individualized for each study, to ensure that the consent form, in its entirety, contains all the information required by 21 CFR50.25 in language the subject can understand. Many IRBs reprocess or retype the completed form to enhance its readability by the subjects. The form finally approved by the IRB should be an exact copy of the form that will be presented to the research subject. The IRB must also review the "process" of informed consent, e.g., the circumstances under which consent will be obtained.

The informed consent regulations (Section 50.25 (a)(5)) require the consent form to include a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and to note the possibility that FDA may inspect the records. Is the statement concerning FDA access to records a waiver of the subject's legal right to privacy? 
No. FDA does not require any subject to "waive" a legal right. Rather, FDA requires that subjects be informed that the "legal right" to complete privacy does not apply in the context of research involving FDA regulated products. Under the authority of the Federal Food, Drug, and Cosmetic Act, FDA can inspect and copy clinical records in order to verify information submitted by a sponsor. Ordinarily it is not necessary that a subject's name be revealed to the FDA investigator unless a more detailed study of the case is required or there is reason to believe that the records do not represent the actual cases studied or results obtained. When an individually identifiable medical record is copied and reviewed by the Agency, the record is properly safeguarded within FDA and is used or disseminated under conditions that protect the privacy of the individual consistent with laws relating to public disclosure of information and the law enforcement responsibilities of the Agency. It should be noted that the records referred to are not those usually kept by the IRB.

Does an IRB or institution have to compensate subjects if injury occurs as a result of participation in a research project?
No. The FDA informed consent regulation (21 CFR 50.25(a)(6)) requires that for research involving more than minimal risk, the subject must be told whether any compensation and any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained. Institutional policy, not FDA regulations, determines whether compensation and medical treatments will be offered and the conditions that might be placed on subject eligibility for compensation or treatments.

Can an IRB require that the sponsor of the study and/or the clinical investigator study's be identified on the study's consent form? 
Yes. The FDA requirements for informed consent are the minimum basic elements of informed consent that must be presented to a research subject (21 CFR 50.25). An IRB can require that any additional information be provided which it considers important to a subject's decision to participate in a research study.


III. OTHER

What is a "general assurance"? Is it required by FDA?
The term "general assurance" is now referred to as a "multiple project assurance"; a "multiple project assurance" is an assurance issued in accordance with Department of Health and Human Services (HHS) regulations on or after January 26, 1981. HHS regulations require a written assurance from an institution that for research involving human subjects conducted by HHS or supported in whole or in part by HHS (e.g., by grant, contract, cooperative agreement, or fellowship) the institution will comply with the HHS protection of human subjects regulations (45 CFR 46). The assurance mechanism is described in 45 CFR 46.103. Once an institution's assurance has been received by the Department, an assurance number is assigned to the institution. The assurance may be for a single project or for multiple projects; multiple project assurances which have been accepted are published in a cumulative list. The Office for Protection from Research Risks, National Institutes of Health, is responsible for implementing the HHS regulations. Its address and telephone numbers are: 9000 Rockville Pike, Bethesda, MD 20205; (301) 496-7005. FDA regulations (21 CFR 50 and 56) apply to research involving products regulated by FDA--federal funds do not need to be involved for the FDA regulations to apply. Although the HES (45 CFR 46) and FDA regulations (21 CFR 50 and 56) are very similar (see the information sheet entitled: "Significant Differences in HHS and FDA Regulations for IRBs and Informed Consent"), FDA regulations do not require an assurance. However, when research involving products regulated by the Agency is funded by HHS, an institution would need to comply with both the NHHS and FDA regulations.

Does an IRB need to register with FDA?
Currently, FDA does not require registration. 
For further information, please contact:

Bonnie M. Lee or James A. Weixel 
Health Assessment Policy Staff 
Office of Health Affairs (EFY-20) 
Food and Drug Administration Room 11-44 
5600 Fishers Lane 
Rockville, Maryland 20857 (301) 443-1382

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