What are the main committees tasked with overseeing a trial?
This figure indicates the three main committees tasked with overseeing a trial, including the Data Safety Monitoring Board (DSMB).
There are 3 statistical roles that need to be filled when a trial requires a DSMB
Trial statistician
All trials should have a statistician who is a member of the Trial Management Group (and often the Trial Steering Committee). The trial statistician is intimately involved with the management and oversight of the trial and is responsible for the statistical aspects of the trial, including contributing to protocol development, writing the statistical analysis plan, reviewing database structure and content, assessment of ongoing data quality, and conducting or overseeing the statistical analysis and the presentation of the final study results.
The trial statistician is often involved in drafting the charter for the DSMB. They may be involved in putting together the open report for the DSMB and the pre-specified format of the closed report but should not prepare or have access to the contents of the closed report. They would normally attend the open but not closed sessions of DSMB meetings, and they do not have voting rights within the DSMB. For blinded trials, the trial statistician should remain blinded to treatment allocation and any interim results until the final analysis of the trial data.
DSMB statistician
This statistician is only a member of the DSMB. Their primary role is to provide independent statistical expertise to the DSMB and help guide interpretation of the DSMB reports. They are required to attend open and closed sessions of DSMB meetings, and have voting rights within the DSMB. They may be unblinded or masked to the treatment allocations via the closed report. This statistician must be independent of the trial and ideally not work in the same research institutes as the trial investigators. The role does not usually involve conducting any analysis or preparing reports for the DSMB.
Reporting statistician
This statistician prepares the closed reports and may contribute aggregated summaries for the open reports for the DSMB. They have access to unblinded treatment group information throughout the trial. They may attend the open session of DSMB meetings, taking care to minimise their contributions due to unconscious bias from any knowledge of interim results. They often contribute to the first part of the closed session where unblinded results are considered by members of the DSMB but then leave the meeting while the DSMB discussion takes place. They do not have voting rights within the DSMB. The reporting statistician is often employed in the research team of the coordinating trial investigator, but should not be involved with the day-to-day conduct and oversight of the trial.
These roles are distinct and should be filled by 3 separate statisticians. Funding is required for the trial and reporting statisticians, although members of the DSMB are seldom renumerated for investigator-led trials. The trial statistician and reporting statistician are usually members of one of the institutes co-ordinating the trial. The DSMB statistician should be external.
If your trial requires a statistician to sit on a DSMB, ACTA STInG have created a list of potential statisticians with experience of contributing to DSMBs on their Find a Statistician database<hyperlink>.
ACTA-STInG also has a mentoring scheme for statisticians to gain experience in DSMBs.
DSMBs for adaptive trials
By their nature, adaptive trials require a lot more statistical support than a standard non-adaptive trial. In particular, they often require regular statistical analysis and monitoring. In this context it is common to have an analytic team (AT) that conducts the regular pre-specified unblinded analyses for the DSMB, which may involve both blinded and unblinded reports.
At least one member of the AT will attend the closed sessions of the DSMB meetings and present the interim results and evaluations of the decision criteria, indicating whether a threshold has been met for a trial adaptation. The AT may also provide additional ongoing trial information, summaries and analyses to the DSMB at the request of the Chair of the DSMB. However, it is the responsibility of the Chair of the DSMB to communicate concerns over adverse event reports or recommendations for trial adaptations to the Chair of the TSC. Adaptive trials often require more support from the DSMB than a non-adaptive design, such as a greater frequency of meetings and the ability to understand and interpret complex statistical models and decision criteria.
Members of the AT who are unblinded must be independent of the day-to-day running of the trial. There may also be a Statistical Subcommittee who form part of the Trial Steering Committee. The Statistical Subcommittee may comprise of non-independent and independent members, and must remain blinded to trial results from the repeat interim analyses.
Given the complexity of adaptive trials, it is important to consider the level of statistical support and the roles required when designing and planning such a study.
If your trial requires a statistician to sit on a DSMB, search here to find <hyperlink> a potential DSMB statisticians, including a number who have experience with adaptive trials.
The ACTA-STInG DSMB mentoring scheme for statisticians is also a great way to gain experience in DSMBs for adaptive trials.