Adherence to Good Clinical Practices - ICH E6

The University of Utah also adheres to Good Clinical Practice (GCP) guidelines described in the International Conference on Harmonization (IHC) E6 guidance for clinical trials that are FDA-regulated. The Good Clinical Practices document describes the ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve human subjects. Clinical trials should be conducted in accordance with these principles (originating from The Declaration of Helsinki).  

Below is an outline of the sections of Good Clinical Practices ICH-E6 to which the University of Utah does not strictly adhere, but where the University has chosen to fulfill these requirements according to standards set forth by the Department of Health and Human Services (DHHS) and the Food and Drug Administration (FDA).

Section 3.3.8(c)
The University of Utah policy on adverse event reporting requires that investigators promptly report all adverse events that represent unanticipated problems involving risks to participants or others.  Unanticipated problems are defined as those events that are considered (1) unknown or unforeseen; (2) related to the research intervention, investigational agent(s), or other research study procedure; and (3) suggest that the research places subjects or others are greater risk of harm than was previously known or recognized.

This policy is consistent with the Guidance for Clinical Investigators, Sponsors, and IRBs on Adverse Event Reporting to IRBs – Improving Human Subject Protection, released by the U.S. Department of Health and Human Services, the FDA, as well as the Good Clinical Practice Program under the FDA.

As such, the IRB does not require investigators to report “all adverse drug reactions (ADRs) that are both serious and unexpected,” unless the adverse drug reactions also meet the definition of an unanticipated problem as described above.

Section 3.3.9(b)
It is University of Utah policy to notify the investigator in writing concerning the reasons for IRB decisions and opinions for the following determinations:
         (a)  Unanticipated problems involving risks to participants or others
         (b)  Serious and continuing non-compliance
         (c)  Tabled study decisions
         (d)  Study disapprovals
         (e)  Suspensions and terminations of research

The IRB does not, however, routinely inform investigators in writing concerning other decisions or opinions made during the review of research, including justification for minor revisions to research and the reasons for approval of research. 

As the IRB adheres to federal regulations describing the Criteria for IRB Approval of Research, these criteria are the basis for all determinations and opinions.  The University of Utah Human Research Protection Program informs the research community of these policies and criteria via training sessions and the IRB website

Section 4.3.3
GCP recommends that investigators "inform the subject's primary physician about the subject's participation in the trial if the subject has a primary physician and if the subject agrees to to the primary physician being informed."  University of Utah policy does not define situations in which investigators must notify a subject's physician of participation in a trial.  The University of Utah IRB relies upon investigators to identify appropriate situations for notifying a subject's physician and describe such circumstances in the IRB application.  The IRB may also require this as a condition of IRB approval on a case-by-case basis. The IRB notes that clinical trial participation information may be stored in a subject's electronic medical record at the University Hospitals and Clinics (see IRB SOP 505) and at the SLC VA (see VHA Handbook 1200.05, Flagging a VHA Health Record), which serves to notify other health care providers who may be providing care to these subjects.  

Section 4.4.2
The University of Utah IRB requires the investigator to submit a current copy of the Investigator’s Brochure for the majority of drug/biologic studies, where an Investigator’s Brochure is available.  However, the IRB does not require an Investigator’s Brochure to be submitted if the study sponsor is considered a sponsor-investigator, as outlined in 21 CFR 312.55 and according to the definition of a sponsor-investigator outlined in 21 CFR 312.3.

Section 4.8.10(e)
The University of Utah IRB does not require investigators to inform subjects of the subject responsibilities during the trial.  The University of Utah IRB does require that the informed consent process and informed consent document include a description of the study procedures that must be followed, as well as the expectations for subject withdrawal/termination, as required by 45 CFR 46.116(a)(1) and (b)(4) as well as 21 CFR 50.25(a)(1) and (b)(4).

Section 4.8.10(i)
The University of Utah IRB requires all investigators to inform subjects of the alternative procedures or courses of treatment, if any, that might be advantageous to the subject, as required by 45 CFR 46.116(a)(4) as well as 21 CFR 50.25(a)(4).  However, the IRB does not require investigators to inform the subjects in writing of the important potential benefits and risks of these alternative treatments.