August 2007
The conduct of clinical trials has moved increasingly to a model that involves multiple sites in many countries. In 1996, the Expert Working Group (Efficacy of the International Conference on Harmonisation of Technical Requirements for registration of Pharmaceuticals for Human Use (ICH) developed “Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance” (GCP). The goal was to provide guidance that would “provide a unified standard for the European Union (EU), Japan, and the United States to facilitate the mutual acceptance of clinical data by regulatory authorities in these jurisdictions.” As you will note in the title of the document, it applies to “Industry.” Sponsors often ask JHU and JHM researchers if they will provide assurance that the institution, the IRBs, and the researchers will comply with GCP as detailed in the ICH document. GCP standards contained in the ICH document are not regulatory requirements in the U.S. JHU and JHM IRBs do not voluntarily agree to comply with all of the GCP statements outlined in this document, as noted below. The JHM IRBs operate in accord with ICU guidelines only to the extent that they are compatible with FDA and DHHS regulations. GCP Guidance: 3. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) 3.1 RESPONSIBILITIES 3.1.2 The IRB/IEC should obtain the following documents: Trial protocol(s)/amendment(s), written informed consent form(s) and consent form updates that the investigator proposes for use in the trial, subject recruitment procedures (e.g., advertisements), written information to be provided to subjects, Investigator's Brochure (IB), available safety information, information about payments and compensation available to subjects, the investigator’s current curriculum vitae and/or other documentation evidencing qualifications, and any other documents that the IRB/IEC may require to fulfill its responsibilities. Differences at JHM: The investigator’s current curriculum vitae is not requested at the time of submission of the protocol. (See below 3.1.3. for additional information) The IRB/IEC should review a proposed clinical trial within a reasonable time and document its views in writing, clearly identifying the trial, the documents reviewed, and the dates for the following: - Approval/favorable opinion
- Modifications required prior to its approval/favorable opinion;
- Disapproval/negative opinion; and
- Termination/suspension of any prior approval/favorable opinion.
Differences at JHM: All of the above information is maintained in the IRB files and/or in the data base; however not all of the information is reiterated in the written IRB notifications to the principal investigator. GCP Guidance 3.1.3 The IRB/IEC should consider the qualifications of the investigator for the proposed trial, as documented by a current curriculum vitae and/or by any other relevant documentation the IRB/IEC requests. Differences at JHM: The investigator’s current curriculum vitae is not requested at the time of submission of the protocol. The qualifications of the investigator are confirmed by the University Faculty Appointment process, which is not conducted by the Office of Human Subjects Research. GCP Guidance 3.2 COMPOSITION, FUNCTIONS AND OPERATIONS 3.2.2 The IRB/IEC should perform its functions according to written operating procedures, should maintain written records of its activities and minutes of its meetings, and should comply with GCP and with the applicable regulatory requirement(s). Differences at JHM: By virtue of not meeting all ICH requirements, it could be considered that the JHM IRBs are not fully GCP compliant. GCP Guidance 3.3 PROCEDURES 3.3.8 Specifying that the investigator should promptly report to the IRB/IEC: (c) All adverse drug reactions (ADRs) that are both serious and unexpected. Differences at JHM: The JHM IRBs do not review all serious and unexpected adverse drug reactions (ADRs) regardless of relatedness. ADR’s are reviewed if, in the opinion of the investigator, they are serious, unexpected and reasonably related to the research. JHM investigators are required to promptly report unanticipated problems, including ADRs, occurring at Hopkins and non-Hopkins institutions that may represent risks to participants or others as defined in the JHM policy No. 103.6(b). Death of a JHM participant must be report as defined in the JHM policy No. 103.6(b)(i). GCP Guidance 4. INVESTIGATOR GCP 4.1.3 The investigator should be aware of, and should comply with, GCP and the applicable regulatory requirements. Differences at JHM: The Organization does not require investigators to complete GCP training or to be aware of all GCP requirements. Investigators may take GCP training on a voluntary basis. GCP 4.8 INFORMED CONSENT OF TRIAL PARTICIPANTS 4.8.10 Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include explanations of the following: (i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their important potential benefits and risks. Differences at JHM: The JHM IRBs require that the alternate procedures or course of treatment are included in the consent document but does not require that the description include potential benefits and risks of each alternative. The participant is encouraged to talk with their physician regarding benefits and risks associated with alternatives. (t) The approximate number of subjects involved in the trial. Differences at JHM: The JHM IRBs consider information about the number of participants be included in the consent document an optional consent element in accord with DHHS 45 CFR 46 and FDA 21 CFR 50. In practice, many of the consent forms approved by the IRBs do contain this information.
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