A benefit-risk Model to Facilitate DMC-sponsor Communication and Decision Making
In drug development, independent data monitoring committees (DMCs) are routinely engaged by clinical trial sponsors to monitor patient safety. Transferring the obligation of interim data monitoring to an independent party helps ensure trial integrity by allowing the sponsor to remain blinded to emerging treatment results. But it also poses a dilemma: after each interim analysis, the DMC makes a recommendation to the sponsor regarding the continuation or modification of the ongoing trial, on the basis of which the sponsor must make a decision. Yet the unblinded results, which alone are the ideal basis for decision making, are only seen by the DMC and by design are withheld from the sponsor. We propose application of a multiattribute benefit-risk model to enable more informed decision making. The model provides an assessment of the emerging benefits and risks of active therapy versus control, based on an evaluation of attributes prespecified by the sponsor. While revealing no specific study outcomes, it allows an appreciation of the direction and magnitude of differentiation between treatment groups in terms of benefit and risk, enabling conversations around scenarios that would lead to this kind of assessment. The model also reflects uncertainty in the evaluation of benefits and risks, an essential feature in the analysis of interim data. This type of assessment may be leveraged to provide meaningful context accompanying the textual recommendation of a DMC to enable more informed decision making, while upholding the sponsor’s commitment to remain blinded to particular study results.
KeywordsData monitoring committee Multiattribute model Beneft-risk Blinding
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- 2.CHMP. Guideline on data monitoring committees. 2005. http://www.emea.europa.eu/pdfs/human/ewp/587203en.pdf (accessed February 3, 2011).Google Scholar
- 3.Food and Drug Administration. Guidance for clinical trial sponsors: establishment and operation of clinical trial data monitoring committees. 2002. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm127073.pdf (accessed February 3, 2011).Google Scholar
- 5.Sashegyi AI. Role of the data monitoring committee and sponsor in monitoring adaptive designs. Pharm Outsourcing. 2010;11:28–31.Google Scholar