The Guideline for Good Clinical Practice (GCP) is a set of guidelines written by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). These guidelines are intended to set “ethical and scientific quality standards for designing, conducting, recording and reporting trials that involve the participation of human subjects.” The principles laid forth in the guidelines are intended to complement the FDA Code of Federal Regulations (CFR) for clinical research being conducted in the United States.
Good Clinical Practice Guidelines vs. Reality
We have a seemingly infinite number of guidelines and regulations on how to conduct research. Shouldn’t all studies then run perfectly since we have all of these “rules” to follow? The truth of the matter is, that even with the vast amount of guidance, rules, and literature on the standards by which to conduct research, there still remains the challenge of how sponsors, investigators, and even FDA inspectors interpret them.
For example, we know that GCP 4.1.5 states, “The investigator should maintain a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties.” Yet sponsors, CROs, and investigators have developed Delegation of Authority/Site Signature Logs whose elements may differ vastly from one another.
Is one version more compliant than the other? It is current industry standard to list at minimum: start/stop dates, tasks to be delegated, PI initials/date (start/stop), and staff signature. Good clinical practice guidelines do not specifically require all of these elements be present on “the list,” yet the industry has progressively interpreted the intent of the statement to be more comprehensive. When left to interpret another’s intention, we enter what I like to refer to as “the gray zone.”
Another example can be found in 4.2.4, which states, “The investigator should ensure that all persons assisting with the trial are adequately informed about the protocol, the investigational product(s), and their trial-related duties and functions.” Again, we see vastly different interpretations of how this should be performed and documented. The interpretation of “adequately informed” may show up as a sponsor’s SOP requiring their CRA perform an in-person SIV at an investigator site rather than a virtual meeting or webex. Or it may be interpreted differently by an investigator site, who considers self-study of a protocol by the staff as meeting the intent of “adequately informed.”
Navigating the Good Clinical Practice Guideline Gray Zone
Is there a map to find our way out of the gray zone and toward specific universal standards (similar to GMP, perhaps?)? There have been some strides made, which have resulted in various guidance documents released by the FDA, and most recently, the release of ICH E6 (R2), which provide some clarity on certain topics; however, we are still left with quite a bit of gray for us to navigate. To learn more about DaVita’s commitment to conducting quality clinical studies, visit our site today.