Medical device sponsors, according to 21 CFR 812.40 and 812.46, are responsible for monitoring clinical trials. The regulations require that sponsors monitor a trial at a site by ensuring that an investigator is compliant with the federal regulations, agreements with the sponsor, the investigational plan, and the requirements set forth in the approval of the study by the IRB. It is also the responsibility of the sponsor, according to 21 CFR 812.43(d) to select monitors qualified by training and experience to monitor a study in accordance with 812 and other applicable FDA regulations. Sponsors may also appoint other individuals and groups to ensure compliance and proper clinical trial monitoring as well as evaluate the accumulating outcome data. The FDA guidance, The Establishment and Operation of Clinical Trial Data Monitoring Committees for Clinical Trial Sponsors, defines a Data Monitoring Committee (DMC), also known as Data Safety Monitoring Boards (DSMBs) or Data and Safety Monitoring Committees (DSMCs), as a group of individuals with pertinent expertise that reviews, on a regular basis, data from one or more ongoing clinical trials. Additionally,
Advisethe sponsor on continuing safety of the trial subjects and those yet to be recruited
- Provide continuing validity and scientific merit of the study
Since the 1960’s, when DMCs were initially initiated for the use of large, randomized, multi-centered trials supported by federal agencies, few medical device sponsors used expert, unbiased, external review committees. Recently, there has been an increase, according to the guidance, for the following reasons:
- A growing number of industry-sponsored trials with mortality or major morbidity endpoints
- Increasing sponsor collaboration between industry and government
- Heightened awareness in the industry in clinical trial conduct and analysis that may lead to inaccurate or biased results
- IRB concerns regarding trial monitoring and patient safety of multi-centered trials
Other oversight groups, such a Clinical Events Committee (CEC), may be delegated by the sponsor for shared responsibilities of clinical monitoring and oversight. All reviewing groups are components to ensure that the sponsor is compliant with conducting trials that are ethical, are safe for the subjects, and produce good, reliable data. For certain trials, sponsors may choose a CEC to review important endpoints reported by the investigators to determine if they meet protocol-specific criteria. Information that a CEC might be:
- Relatedness and seriousness of adverse events
- Imaging data
- Autopsy reports
CECs are most valuable when endpoints are subjective; require the application of a complex definition, or when the intervention is not blinded. CECs do not typically provide interim comparisons similar to DSMB reviews. CEC assessments can help to ensure that data reviewed by other committees are accurate and as free of bias as possible.
Although DSMBs and CECs are similar in that they provide clinical oversight and monitoring of a trial, their function is slightly different as delegated by the sponsor. Do your trials have a CEC or DSMB? How do you ensure adequate monitoring and clinical oversight? Please share here.
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