Guidance for Institutional Review Boards and Clinical Investigators
FDA requires that an Institutional Review Board (IRB) review and have authority to approve, require modifications in, or disapprove all research activities covered by the IRB regulations [21 CFR 56.109(a)]. An IRB is required to ensure that appropriate safeguards exist to protect the rights and welfare of research subjects [21 CFR 56.107(a) and 56.111]. In fulfilling these responsibilities, an IRB is expected to review all the research documents and activities that bear directly on the rights and welfare of the subjects of proposed research. The protocol, the consent document and, for studies conducted under the Investigational New Drug (IND) regulations, the investigator's brochure are examples of documents that the IRB should review. The IRB should also review the methods and material that investigators propose to use to recruit subjects.
Direct advertising for research subjects, i.e., advertising that is intended to be seen or heard by prospective subjects to solicit their participation in a study, is not in and of itself, an objectionable practice. Direct advertising includes, but is not necessarily limited to: newspaper, radio, TV, bulletin boards, posters, and flyers that are intended for prospective subjects. Not included are: (1) communications intended to be seen or heard by health professionals, such as "dear doctor" letters and doctor-to-doctor letters (even when soliciting for study subjects), (2) news stories and (3) publicity intended for other audiences, such as financial page advertisements directed toward prospective investors.
IRB review and approval of listings of clinical trials on the internet would provide no additional safeguard and is not required when the system format limits the information provided to basic trial information, such as: the title; purpose of the study; protocol summary; basic eligibility criteria; study site location(s); and how to contact the site for further information. Examples of clinical trial listing services that do not require prospective IRB approval include the National Cancer Institute's cancer clinical trial listing (PDQ) and the government-sponsored AIDS Clinical Trials Information Service (ACTIS). However, when the opportunity to add additional descriptive information is not precluded by the data base system, IRB review and approval may assure that the additional information does not promise or imply a certainty of cure or other benefit beyond what is contained in the protocol and the informed consent document.
FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection process. Advertisements should be reviewed and approved by the IRB as part of the package for initial review. However, when the clinical investigator decides at a later date to advertise for subjects, the advertising may be considered an amendment to the ongoing study. When such advertisements are easily compared to the approved consent document, the IRB chair, or other designated IRB member, may review and approve by expedited means, as provided by 21 CFR 56.110(b)(2). When the IRB reviewer has doubts or other complicating issues are involved, the advertising should be reviewed at a convened meeting of the IRB.
FDA expects IRBs to review the advertising to assure that it is not unduly coercive and does not promise a certainty of cure beyond what is outlined in the consent and the protocol. This is especially critical when a study may involve subjects who are likely to be vulnerable to undue influence. [21 CFR 50.20, 50.25, 56.111(a)(3), 56.111(b) and 812.20(b)(11).]
When direct advertising is to be used, the IRB should review the information contained in the advertisement and the mode of its communication, to determine that the procedure for recruiting subjects is not coercive and does not state or imply a certainty of favorable outcome or other benefits beyond what is outlined in the consent document and the protocol. The IRB should review the final copy of printed advertisements to evaluate the relative size of type used and other visual effects. When advertisements are to be taped for broadcast, the IRB should review the final audio/video tape. The IRB may review and approve the wording of the advertisement prior to taping to preclude re-taping because of inappropriate wording. The review of the final taped message prepared from IRB-approved text may be accomplished through expedited procedures. The IRB may wish to caution the clinical investigators to obtain IRB approval of message text prior to taping, in order to avoid re-taping because of inappropriate wording.
No claims should be made, either explicitly or implicitly, that the drug, biologic or device is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other drug, biologic or device. Such representation would not only be misleading to subjects but would also be a violation of the Agency's regulations concerning the promotion of investigational drugs [21 CFR 312.7(a)] and of investigational devices [21 CFR 812.7(d)].
Advertising for recruitment into investigational drug, biologic or device studies should not use terms such as "new treatment," "new medication" or "new drug" without explaining that the test article is investigational. A phrase such as "receive new treatments" leads study subjects to believe they will be receiving newly improved products of proven worth.
Advertisements should not promise "free medical treatment," when the intent is only to say subjects will not be charged for taking part in the investigation. Advertisements may state that subjects will be paid, but should not emphasize the payment or the amount to be paid, by such means as larger or bold type.
Generally, FDA believes that any advertisement to recruit subjects should be limited to the information the prospective subjects need to determine their eligibility and interest. When appropriately worded, the following items may be included in advertisements. It should be noted, however, that FDA does not require inclusion of all of the listed items.
- the name and address of the clinical investigator and/or research facility;
- the condition under study and/or the purpose of the research;
- in summary form, the criteria that will be used to determine eligibility for the study;
- a brief list of participation benefits, if any (e.g., a no-cost health examination);
- the time or other commitment required of the subjects; and
- the location of the research and the person or office to contact for further information.
The first contact prospective study subjects make is often with a receptionist who follows a script to determine basic eligibility for the specific study. The IRB should assure the procedures followed adequately protect the rights and welfare of the prospective subjects. In some cases personal and sensitive information is gathered about the individual. The IRB should have assurance that the information will be appropriately handled. A simple statement such as "confidentiality will be maintained" does not adequately inform the IRB of the procedures that will be used.
Examples of issues that are appropriate for IRB review: What happens to personal information if the caller ends the interview or simply hangs up? Are the data gathered by a marketing company? If so, are names, etc. sold to others? Are names of non-eligibles maintained in case they would qualify for another study? Are paper copies of records shredded or are readable copies put out as trash? The acceptability of the procedures would depend on the sensitivity of the data gathered, including; personal, medical and financial.