Building a More Connected DSMB: Better Integrating Ethics Review and Safety Monitoring

Abstract

Data and Safety Monitoring Boards (DSMBs) have become an increasingly common feature of clinical trial oversight, yet a paucity of legal or ethical frameworks govern these Boards' composition or operation, or their relationship with other actors with monitoring responsibilities. This paper argues that prevailing structural gaps are impeding harmonized systems for monitoring the ongoing ethical acceptability of clinical trials. Particular tensions stem from DSMBs' sweeping discretion in deciding whether and when to recommend that a trial should be terminated or amended based on safety and efficacy information. This discretion becomes especially challenging in light of DSMBs' monopoly over emerging trial data, which prevents Institutional Review Boards, sponsors, and investigators from participating in certain pivotal and ethically charged decisions. To address these disconnects, I advocate for strengthened pre-trial and post-trial communication in addition to innovative strategies to support DSMB decision making through the life of a trial.

Data and Safety Monitoring Board and the Ratio Decidendi of the Trial

“…Korn and Freidlin go a step further than standard guidelines by proposing not just reporting what interim rule was used, "but explaining why formal monitoring was not used if it was not" (2011,6). Very little evidence exists about how DSMBs are making interim decisions and why they are not following reporting guidelines (Eckstein 2015). My proposal differs from the guideline literature because it makes reference to a comparable and desirable functioning system of cases, rules and obligation, namely, judge-made law in common law.…”

“…Despite consenting to the monitoring plan, the DSMB has sweeping discretion over whether or not it ought to follow its own agreed-upon rules during trial conduct. Given that the DSMB has an information monopoly during all interim analysis, also having sweeping discretion over the course of the trial precludes most meaningful oversight of its decision-making (Eckstein 2015). Decision-making discretion by the DSMB becomes particularly challenging given the added fact that most of its deliberations happen behind closed doors, routinely not reporting publicly its interim decision reasons and recommendations (Wittes 1993).…”

Of Straws, Camels, Research Regulation, and IRBs

“…Communication between IRBs and DSMBs is often insufficient as well, leading to gaps in oversight. Their relationship has been described as a “largely passive, one-way information exchange, usually mediated through a trial investigator.” 38 Despite their shared interests and regulations that explicitly lay out reporting requirements from DSMBs to IRBs, the small amount of communication that does occur between them has been found to be largely inconsistent. 61 This is especially worrisome because of the distinct goals of these committees mentioned above.…”

Quantitative Framework for Retrospective Assessment of Interim Decisions in Clinical Trials

“…Given that the DSMB has an information monopoly during all interim analysis, also having sweeping discretion over the course of the trial precludes most meaningful oversight of its decision making. 15 Decision-making discretion by the DSMB becomes particularly challenging given the added fact that most of its deliberations happen behind closed doors, routinely not reporting publicly its interim decision reasons and recommendations. 16 …”

“…Given that the DSMB has an information monopoly during all interim analysis, also having sweeping discretion over the course of the trial precludes most meaningful oversight of its decision making. 15 Decision-making discretion by the DSMB becomes particularly challenging given the added fact that most of its deliberations happen behind closed doors, routinely not reporting publicly its interim decision reasons and recommendations. 16 Although there are practical reasons for DSMBs to keep interim data analysis private under the premise of confidentiality, secret DSMB decision making has at least one important shortcoming: the lack of publicity in decision making prevents the public from getting a proper understanding of the reasons for the DSMB findings and final recommendation.…”