FDA outlines risk-based approach to monitoring clinical trials

The US Food and Drug Administration (FDA) issued final guidance meant to assist drug and medical device makers in developing risk-based monitoring strategies for clinical investigations involving drugs, biologics and medical devices in the middle of April 2023.  The question-and-answer format document states that “clinical investigation monitoring is a quality control tool for determining whether investigation activities are being carried out as planned.  This guidance contains recommendations on planning a monitoring approach, developing the content of a monitoring plan, and addressing and communicating monitoring results.”

The final guidance has been substantially revised from an earlier draft issued in March 2019.  The document also expands on FDA’s August 2013 guidance for industry entitled “Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring” by providing additional information to facilitate sponsors’ implementation of risk-based monitoring.

The final version differs from the draft in placing more emphasis on data integrity in clinical trial monitoring.  In the background section, it adds text stating that “this system to manage the quality of the investigation should help ensure data integrity while safeguarding the rights, safety, and welfare of trial participants, for example, by focusing on the design of efficient clinical trial protocols, tools for identifying and tracking potential risks, and procedures for data collection and processing.”

The final version also provides new information to the question: “Should sponsors monitor only risks that are important and likely to occur?”  The text responds with a new answer:  “No.  Sponsors should monitor the important and likely risks identified during their initial risk assessment, and they should also monitor for additional risk detected during the conduct of the clinical investigation that were not identified before the investigation began.”

The revision also updates the information to the question:  “How can a risk-based approach to monitoring that includes centralized monitoring help minimize missing data or protocol deviations?”  The guidance now states that “centralized monitoring is a systematic analytical evaluation of study conduct across multiple clinical sites, carried out by sponsor personnel or representatives (e.g., clinical monitors, data management personnel, or statisticians).  Centralized monitoring may allow sponsors to conduct the following:

(1)        review study-wide data for inconsistencies or omissions;

(2)        perform activities such as data checks, for completeness and consistency;

3)         verify source data;

(4)        ensure that Institutional Review Board (IRB) and Informed Consent (IC) documents are current; and

(5)        determine which clinical sites need on-site review.”

REFERENCE:  Regulatory Focus (A RAPS publication) ; 11 APR 2023; Joanne S. Eglovitch