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Trial Steering Committee
The function of a Trial Steering Committee (TSC) is to provide independent oversight of all aspects of a clinical trial including trial progress, adherence to protocol and review of any new information regarding the study intervention or therapeutic area. The TSC is usually chaired by an independent expert in the field and should include a majority of members who are not involved in running the trial.
Data and Safety Monitoring Board
Independent Data and Safety Monitoring Boards (DSMB) address research participant safety and protection by assessing the progress of a trial. Alternative terms for DSMBs are sometimes used, the most common being ‘Data Monitoring Committees’ (DMC) and ‘Independent DMCs’ (IDMC).
The DSMB is responsible for interim analyses of study data pertaining to the safety and the critical efficacy endpoints. The board then makes recommendations to the study sponsor regarding whether the trial can continue or if it needs to be modified or terminated. A priority for such a board is to protect the research subjects from unexpected adverse reactions, and to ensure that the participants do not have unnecessarily prolonged exposure to an inferior therapy, or that the trial does not continue beyond the point at which an investigational therapy is demonstrated to be effective or the endpoint has been reached.
DSMB members must be free from conflict of interest with respect to the studies they will be expected to review. The composition of the board must also reflect the disciplines and medical specialties necessary to interpret data from the studies being monitored and in particular to fully evaluate the safety of participants in those studies.
Endpoint Review Committee
It might seem that open trials are more straightforward than randomised trials but in reality they can be more complex and more challenging because of the rigor that is needed to avoid bias, and to protect the integrity of the data and final outcome of the trial. However in any trial design it is worth thinking through how the endpoints will be defined and captured and how they will be assessed by the clinical team as this is crucial to the success of the trial. In multi-centre trials the possible consequences of inaccurate endpoint assessment or definition are likely to be greater.
Endpoint review committees are most typically used in open trials to ensure that the endpoints that are attributed and assessed by the bedside team are accurate, appropriate and unbiased and, ultimately, that the trial has produced the right answer.
In clinical trials, particularly open ones, investigators may report certain events more than others because they expect them. This can happen unintentionally because this outcome is expected and therefore perhaps being noticed more or simply because the trial has raised awareness and possibly improved training. The point is that it is a subjective judgement and so could lead to errors. Over or under reporting of an event can lead to a false result in a trial. Equally, too many wrong diagnoses can lead to a trial not being able to show a difference. This is because the ability to demonstrate a true difference between randomised groups will be made weaker by incidences of wrong assessments in either group.
Therefore, establishing an independent endpoint review committee that can review the trial data along with any other history will provide a level of confidence that the assessments and assignments of endpoints are correct. Typically the endpoint review committee has two to four members comprising of an independent chair, an expert in the disease being studied and a member of the trial management or steering committee. A short remit for the endpoint review committee should be drafted by the trials management group or steering committee and this should set out when and how they meet (this will be also be influenced by the trial’s analysis plan), what trial data and other information they will receive, and how they should report their findings.
To visit out Templates library and download relevant documents, including a DSMB Charter, please click on this link.
References
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Pazdur, R., Endpoints for assessing drug activity in clinical trials. The oncologist, 2008. 13(Supplement 2): p. 19.
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McGarvey, L.P., et al., Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee. Thorax, 2007. 62(5): p. 411-5.