FDA issues new draft guidance on data monitoring committees

The US Food and Drug Administration (FDA) on Monday issued a new draft guidance advising certain product sponsors to establish data monitoring committees (DMCs) to ensure that safety signals are detected early. In the past, DMCs were typically seen in clinical trials for serious diseases with “significant morbidity or mortality,” though the agency said that has changed in recent years and that new guidance is needed to advise sponsors on their proper use.

The draft guidance is meant to help clinical trial sponsors figure out when DMCs may be needed and applies to sponsors responsible for managing clinical trials and may potentially apply to third parties who are delegated the task of trial management. The guidance will replace the agency’s 2006 final guidance Establishment and Operation of Clinical Trial Data Monitoring Committees when finalized.

DMCs are sometimes called data and safety monitoring board (DSMB), data and safety monitoring committee (DSMC), and independent data monitoring committee (IDMC). As FDA notes, they’ve been in use since the 1960s and are used by drug sponsors to monitor clinical trial procedures and practices independently, evaluate early efficacy data, and determine if there are safety concerns that should be addressed.

“A clinical trial DMC is established by a sponsor and is composed of a group of individuals with relevant expertise that reviews accumulating data on a regular basis from one or more clinical trials and recommends to the sponsor whether to continue, modify, or stop a trial or trials,” said FDA.

FDA notes that sponsors historically have not been required to set up DMCs under certain conditions if an institutional review board (IRB) can approve the trial without requiring informed consent from the trial participants and can set up an IDMC.

“Although the use of DMCs initially was more common in disease areas associated with significant morbidity or mortality, since 2006, there has been an increase in the use of DMCs in many disease areas not involving serious morbidity or mortality,” said FDA. “For example, DMCs can provide the specialized expertise to evaluate emerging efficacy and safety data for trials in rare diseases (e.g., certain genetic disorders), for trials in vulnerable populations (e.g., neonates), and for oncologic therapies with highly specific targets and potential serious risks (e.g., biological products for genetic targets, immunotherapies).”

“DMCs are also being used in early phase trials in serious diseases or conditions,” the agency added. “With this growth of DMC use, a variety of approaches to DMC operations has been developed.”

If a DMC reports an increased rate of serious unanticipated adverse events, the sponsor is required to investigate the issue and if it determines there is a “reasonable possibility” that the event is associated with the product, it needs to report those findings to regulators.

In the guidance, FDA lays out when a sponsor should create a DMC and how to develop it.
“An important consideration in determining whether to use a DMC in a development program is whether DMC review is practical for the particular clinical trial,” said FDA. “Although the practicality of having a DMC for long-term trials is well established, it is not as clear for short-term trials.”

“If the trial is likely to complete enrollment quickly and the follow-up period is short, convening a DMC to review interim data to assess continued exposure of subjects to investigational interventions may be impractical and of little value,” the agency added. “Careful consideration should therefore be given to whether a DMC could have a meaningful impact on the conduct of the trial.”

If they do decide to establish a DMC, FDA says sponsors should create a DMC charter detailing the organization's obligations, responsibilities, and standard operating procedures. It also goes into detail about what should be in the charter, such as procedures to assess potential member conflicts of interest, how unblinded data analyses should be prepared for sponsors, and setting up procedures to ensure confidentiality of communication between the sponsor, the DMC and other parties when sharing interim comparative data so it’s not inappropriately disclosed.

Stakeholders can comment on the draft guidance until 13 April on www.regulations.gov under docket no. FDA-2001-D-0219.

FDA draft guidance

FDA issues new draft guidance on data monitoring committees

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