Understanding the functions and operations of data monitoring committees: Survey and focus group findings

Abstract

Background: The use of data monitoring committees in the conduct of clinical trials has increased and evolved, but there is a lack of published information on when data monitoring committees are needed and utilized, the acceptable range of data monitoring committee practices, and appropriate qualifications of data monitoring committee members. Methods: To gain a better understanding of data monitoring committee operations and areas for improvement, the Clinical Trials Transformation Initiative conducted a survey and set of focus groups. A total of 143 respondents completed the online survey: 76 data monitoring committee members, 52 sponsors involved with organization of data monitoring committees, and 15 statistical data analysis center representatives. There were 42 focus group participants, including data monitoring committee members; patients and/or patient advocate data monitoring committee members; institutional review board and US Food and Drug Administration representatives; industry, government, and non-profit sponsors; and statistical data analysis center representatives. Results: Participants indicated that the primary responsibility of a data monitoring committee is to be an independent advisory body representing the interests of trial participants by assessing the risk and benefit ratio in ongoing trials. They noted that data monitoring committees must have access to unmasked data in order to perform this role. No clear consensus emerged regarding specific criteria for requiring a data monitoring committee for a given trial, and some participants felt data monitoring committees may be overused. Respondents offered suggestions for the data monitoring committee charter and communications with sponsors, institutional review boards, and regulators. Overall, data monitoring committee members reported that they are able to function independently and their recommendations are almost always accepted by the sponsor. Participants indicated that there are no standards or guidelines pertaining to qualifications of data monitoring committee members. Furthermore, only 8% (6/72) of data monitoring committee member survey respondents received any formal training, and 94% (68/72) were not aware of any training programs. Conclusion: Findings from the survey and focus groups provide a better understanding of contemporary data monitoring committee operations and insights regarding challenges and best practices. Overall, it was clear that increased training will be needed to prepare the next generation of qualified data monitoring committee members to meet the growing demand. These findings can be used by Clinical Trials Transformation Initiative and others to develop recommendations and tools to improve data monitoring committee operations and the overall quality of trial oversight.

Recommendations for data monitoring committees from the Clinical Trials Transformation Initiative

“…Although training is highly desirable prior to serving on a DMC, the vast majority of our survey respondents indicated that they had not received training and were unaware of DMC-specific training programs. 3 …”

“…sponsors, investigators, and institutional review boards); and (d) identify strategies for preparing the next generation of DMC members. 3 …”

Issues for Masked Data Monitoring

“…Charter [..] should fully address whether the DMC will have access to unmasked data at the subject level and aggregate level. (Calis et al 2017;Lewis et al 2016) 2. Chen-Mok et al described the experiences and challenges in data monitoring for clinical trials within an international tropical disease research network:…”

Enhancing clarity of clinical trial safety reports for data monitoring committees

“…Committee members take on a substantial responsibility for the safety of participants in the study, those yet to be enrolled, and even those who might someday receive the intervention. Numerous challenges associated with this responsibility have been recently described, including the need for training for DMC members and clear DMC reports (Calis et al 2017b(Calis et al , 2017aDavis et al 2018;DeMets and Ellenberg 2016;DeMets and Fleming 2004;Ellenberg and Ellenberg 2018;Ellenberg et al 2002;Fleming et al 2017Fleming et al , 2018Lewis et al 2016;Neaton et al 2018). DMC reports are produced by an independent unmasked statistical team.…”