“The Institutional Review Board (IRB) also known as an Independent Ethics Committee (IEC), Ethical Review Board (ERB), or Research Ethics Board (REB), is a kind of committee that applies research ethics by evaluating the methods used for research to ensure that they are ethical.
These boards are formally designated for the acceptance (or rejection), monitoring and review of human biomedical and behavioral studies.
Does an IRB need to register with FDA before approving studies?
As reported in the Federal Register on 15 January 2009 (74 FR 2358), 21 CFR Section 56, Institutional Review Boards (21 CFR 56.106) was amended in respect of IRB registration. This amendment includes registration for any United States (U.S.) IRB that reviews FDA-regulated studies. Registered information for the IRB is entered in an Internet registration system operated by the Department of Health and Human Services(HHS). ( Guidance for Institutional Review Boards (IRBs) Frequently Asked Questions – IRB Registration).
May a hospital IRB review a study that will be conducted outside of the hospital?
Yes. IRBs may consent to review research from associated or non-affiliated investigators but FDA does not allow IRBs to assume this responsibility. When the IRB performs such reviews regularly, these reviews should be approved by IRB regulations, and the process should be outlined in the written procedures of the IRB.
An IRB hospital may review external studies on an individual basis when the minutes clearly indicate the members are aware of where the study is to be performed and when the IRB has sufficient information about the site(s) of the research.
May IRB members be paid for their services?
The FDA regulations do not prevent a member from being compensated for the services rendered. Payment to the IRB members should not be related to or dependent upon a favorable decision. Expenses, such as travel costs, may also be reimbursed.
What is the FDA role in IRB liability in malpractice suits?
In the case of malpractice cases, FDA laws do not tackle the issue of the IRB or administrative liability. FDA has no power to restrict the duties of IRBs or their leaders. Compliance with FDA regulations may help reduce the exposure of an IRB to liability.
Is the purpose of the IRB review of informed consent to protect the institution or the subject?
The basic aim of IRB review of informed consent is to ensure the protection of the rights and welfare of subjects.
A signed informed consent agreement is evidence that the questionnaire has been (and presumably explained) given to a prospective subject and that the subject has agreed to participate in the study.
IRB review of informed consent documents also ensures that the institution has complied with applicable regulations.
May a clinical investigator be an IRB member?
Yes, nevertheless, the IRB regulations [21 CFR 56.107(e)] prohibit any member from participating in the IRB’s initial or continuing review of any study in which the member has a conflicting interest, except to provide information requested by the IRB.
When selecting the IRB members, the potential for conflicts of interest should be considered. When members may have disagreements, and need to stay away from meetings and abstain from voting, their contributions to the group review process may be minimal, which can hamper the review process.
If this individual becomes chairman of the IRB, even bigger disturbances will result.
If IRB members can not attend a meeting that has been called, should they send anyone from their department to vote for them?
No. Alternates who are formally appointed and specified in the membership roster may replace, but ad hoc replacements as members of an IRB are not allowed.
Moreover, unless the member has obtained a copy of the documents to be discussed at the meeting, a member who can not be present at the convened meeting can participate by video-conference or telephone conference call. Such members may vote and be counted as the part of quorum.
If IRB procedures permit, ad hoc substitutes will serve as consultants and collect information for the absent member, but they may not be counted against the quorum or participate in either a deliberation or a board vote.
Of course, the IRB will ask this representative ‘s questions just as they do from any non-member consultant. Opinions of the absent members that are transmitted by the mail, telephone, telefax or e-mail may be considered by attending IRB members but may not be counted as votes or the quorum for convened meetings.
May the IRB use alternate members?
The FDA allows the use of officially appointed alternate IRB members, as long as the prescribed protocols of the IRB specify the selection and role of the alternate members.
The IRB roster will describe the primary member(s) that may be substituted for by each alternative member.
To ensure that an sufficient quorum is preserved, the credentials of the alternate should be equal to the substituted primary member. The minutes of the IRB will record when a primary member is replaced by an alternative.
If alternates substitute a primary member, the alternate member would have provided and checked the same information that was or should have been provided from the primary member.
Does a non-affiliated member need to attend all IRB meeting?
No. Although 21 CFR 56.108(c) does not directly allow the participation of a member not otherwise associated with the organization to constitute a quorum, the FDA regards the participation of these members as an significant element in the diversity of the IRB. Therefore, FDA is inappropriate for regular absence of all non-affiliated members.
In recognition of their significant role, many IRBs have named more than one member not previously affiliated with the agency. In compliance with 21 CFR 56.107(a), the FDA requires IRBs to recommend representatives who will be willing to participate completely in the IRB process.
Are there regulations requiring clinical investigators to report to the IRB once a study is completed?
IRBs shall act according to written procedures. Some of these procedural conditions [21 CFR 56.108(a)(3)] includes ensuring “a timely recording of changes in a research operation to the IRB.” Completion of the analysis is an operation change and should be reported to the IRB.
While subjects may no longer be “at risk” under the study, a final report / notice to the IRB allows it to close its files and provide information that the IRB can use in reviewing and authorizing relevant studies.
What is expedited review?
Expedited review is a process that allows for the review and approval of certain forms of work without convening an IRB conference. The IRB regulations of the Agency [21 CFR 56.110] authorize, but do not mandate, an IRB to review such research categories through an accelerated process if the study entails only minimal risk.
A list of the categories was last published in the Federal Register on January 27, 1981 [46 FR 8980].
In the time covered by the original approval, the IRB can also use the expedited review process to review minor improvements to previously approved work. Under an expedited review protocol, the IRB chairperson or one or more experienced IRB members appointed by the chairperson may conduct the review of the study.
All IRB authority can be exercised by the Reviewer(s), excluding opposition. Study can only be disapproved by the full committee after review. The IRB is expected to follow a method of keeping all members informed of research studies accepted by expedited review.
Are sponsors allowed access to IRB written procedures, minutes and membership rosters?
The FDA regulations do not allow access to IRB records by the public or by sponsors. FDA does not however prohibit the sponsor from requesting IRB records.
The IRB and the institution may draw up a policy on whether sponsors are given minutes or a relevant portion of the minutes.
Through IRB also needs to be aware of state and local laws about access to IRB records because of variability.
Will a brochure of an investigator be included in the report when an IRB reviews an an investigational drug study?
A brochure by an investigator is typically provided by FDA [21 CFR 312.23(a)(5) and 312.55] for studies performed under an investigational new drug application.
While 21 CFR part 56 does not reference the investigator’s brochure by name, the IRB obviously needs to review most of the information found in those brochures.
The regulations outline requirements for work approval by the IRB. 21 CFR 56.111(a)(1) allows the IRB to ensure that all risks are reduced. 21 CFR 56.111(a)(2) allows the IRB to ensure that the risks to the subjects in relation to the expected benefits are appropriate.
The risks can not be properly measured without evaluating the findings of previous animal and human studies, which are outlined in the brochure of the investigator.
There is no clear legal obligation to send a Brochure of the Investigator to the IRB. There are legal provisions for sending out information that are generally included in the Investigator’s Brochure.
It is normal for the Investigator’s Brochure to be submitted to the IRB, and the IRB may develop written procedures that require it to be submitted.
Brochures from investigators may be part of the study program that the IRB approves while evaluating studies of medical devices.
Does FDA expect the IRB chair to sign the approval letters?
FDA does not specify the procedure to be used by IRBs with respect to the signature of the letter of approval from the IRB. The IRB ‘s written operating procedures should outline the procedure it accompanies.
Are annual IRB reviews required when all studies are reviewed by the IRB each quarter?
For the original and ongoing review of each sample, the IRB records will mention the duration (not to exceed one year) for the next continuing examination in either months or other circumstances, such as after a specified number of subjects have been enrolled.
An IRB may agree, on a quarterly basis, to review all studies. If each quarterly report contains sufficient information for an appropriate continuing review and is reviewed by the IRB under procedures that meet FDA ‘s criteria for continuing review, an additional “annual” review will not be necessary.
Who should be present when the informed consent interview is conducted?
FDA does not require a third person to witness the consent interview except the subject or representative is not given the opportunity to read the consent document before it is signed, (21 CFR 50.27(b)).
The person who conducts the consent interview should be well-informed about the study and able to answer questions. FDA does not identify who this individual should be. Some sponsors and some IRBs require the clinical investigator to personally conduct the consent interview.
On the other hand, if someone other than the clinical investigator conducts the interview and obtains consent, this responsibility should be formally delegated by the clinical investigator and the person so delegated should have received suitable training to perform this activity.
Is the sponsor expected to review the IRB approved consent form to ensure it meets all FDA requirements?
The informed consent for investigational devices is a necessary part of the IDE application. Consequently, it is approved by FDA as part of the IDE application. When an IRB makes substantial changes to the paper, it involves reapproval by the FDA and the sponsor is usually involved in this process.
FDA regulations for other products do not specially require the sponsor to review IRB approved consent documents. Conversely, most sponsors do conduct such reviews to assure the wording is acceptable to the sponsor.
May an IRB require that the sponsor of the study and/or the clinical investigator be identified on the study’s consent document?
Yes. The FDA informed consent criteria are the minimum basic elements of informed consent that must be given to a study subject [21 CFR 50.25]. An IRB may include any additional details that it considers relevant to the decision of a subject to take part in a research study [21 CFR 56.109(b)].
Does FDA require the informed consent document to contain a space for assent by children?
“No, however, many investigators and IRBs consider it standard practice to obtain the agreement of older children who can understand the circumstances before enrolling them in research.
While the FDA regulations do not specifically address enrollment of children (other than to include them as a class of vulnerable subjects), the basic requirement of 21 CFR 50.20 applies, i.e., the legally effective informed consent of the subject or the subject’s legally authorized representative must be obtained before enrollment.
Parents, legal guardians and/or others may have the ability to give permission to enroll children in research, depending on applicable state and local law of the jurisdiction in which the research is conducted.
(Note: permission to enroll in research is not the same as permission to provide medical treatment.)
IRBs generally require investigators to obtain the permission of one or both of the parents or guardian (as appropriate) and the assent of children who possess the intellectual and emotional ability to comprehend the concepts involved.
Some IRBs require two documents, a fully detailed explanation for parents and older children to read and sign, and a shorter, simpler one for younger children. [For research supported by DHHS, the additional protections at 45 CFR 46 Subpart D are also required. The Subpart D regulations provide appropriate guidance for all other pediatric studies.]
On April 24, 2001, FDA issued an interim final rule, Additional Protections for Children, as subpart D to 21 CFR Part 50. Assent by children is addressed in subpart D. This interim final rule and its preamble are available at Additional Protections for Children.”
Do informed consent records have to be translated into native written language to study subjects that don’t understand English?
The signed informed consent document is the approved interview written record. A copy of the consent to be used as a reference document for study subjects is given to confirm their understanding of the study and to communicate with their physician or family members about the study, if needed.
To meet the requirements of 21 CFR 50.20, the consent agreement must be the subject-matter understandable in language. The consent form will be in English, if the prospective subject is fluent in English and the consent interview is performed in English.
However, when the study subject population includes non-English speaking people so that the clinical investigator or the IRB anticipates that the consent interviews are liable to be conducted in a language other than English, the IRB should assure that a translated consent form is prepared and that the translation is accurate.
A consultant can be used to ensure the translation is correct. A copy of the translated consent document shall be made available to each relevant subject. Although a translator may be used to promote communication with the subject matter, a written translation should not be substituted for regular ad hoc translation of the consent document.
Which FDA office may an IRB contact to determine whether an investigational new drug application (IND) or investigational device exemption (IDE) is required for a study of a test article?
For drugs, IRB may contact the Center for Drug Evaluation and Research (CDER), Office of Communications, Division of Drug Information at (301) 796-3400.
For biological products, contact the Center for Biologics Evaluation and Research (CBER), Office of Communication, Outreach and Development, at (800)-835-4709 or (301) 827-1800.
For medical devices, contact the Investigational Device Exemption (IDE) Staff, Office of Device Evaluation, Center for Devices and Radiological Health (CDRH), at (301) 796-5640.