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.
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.
Authors: Susanna E Borggreve; Hans L Hillege; Bruce H R Wolffenbuttel; Paul E de Jong; Mike W Zuurman; Gerrit van der Steege; Arie van Tol; Robin P F Dullaart Journal: J Clin Endocrinol Metab Date: 2006-05-09 Impact factor: 5.958
Authors: J M Ordovas; L A Cupples; D Corella; J D Otvos; D Osgood; A Martinez; C Lahoz; O Coltell; P W Wilson; E J Schaefer Journal: Arterioscler Thromb Vasc Biol Date: 2000-05 Impact factor: 8.311
Authors: K Hirano; S Yamashita; N Nakajima; T Arai; T Maruyama; Y Yoshida; M Ishigami; N Sakai; K Kameda-Takemura; Y Matsuzawa Journal: Arterioscler Thromb Vasc Biol Date: 1997-06 Impact factor: 8.311