Torcetrapib
A post hoc review of the safety monitoring board for the torcetrapib trial warns against over-relying on formal statistical stopping rules (Eur J Clin Pharmacol 2008)
Original title: The conscientious judgement of a DSMB--statistical stopping rules re-examined
Prompted by the failure of the large cardiovascular mortality and morbidity trial of torcetrapib, researchers conducted a post hoc review of the decisions made by that trial's Data and Safety Monitoring Board (DSMB), alongside other studies where DSMBs faced complex decisions, using information the study sponsors submitted to the Medical Products Agency. The review found that these cases illustrate the complexity of DSMB decision-making and indicate that relying too heavily on formal statistical stopping rules risks delaying identification of an emergent safety signal. The authors conclude that multiple approaches to assessing efficacy and safety, potentially including p-value flags and complementary statistical analysis of the likelihood of meeting study objectives given data collected so far, are needed to facilitate earlier stopping of trials with a negative risk-benefit balance.
Original abstract
Objective: In the light of the recent failure of a large cardiovascular mortality and morbidity study with torcetrapib, we have undertaken a post hoc review of the decisions taken by the Data and Safety Monitoring Board (DSMB) in that study. A number of other studies in which complex decisions were made by DSMBs are also reviewed.
Results: The examples illustrate the complexities involved in the decision-making process by DSMBs and indicate that too much reliance on formal statistical stopping rules should be avoided due to a risk of delaying the identification of an unacceptable emergent safety signal.
Methods: The review was based on information submitted by the sponsors of the studies to the Medical Products Agency.
Conclusions: Multiple approaches to assessing the efficacy and safety in clinical trials need to be considered in order to facilitate early stopping of clinical trials with a negative risk benefit balance. Such systems may, for example, include the use of p-value flags and/or a complementary statistical analysis of the likelihood of achieving the study objective based on the data obtained to date.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.