Evidence generation methods & evidence requirements
Methods to improve the efficiency of confirmatory clinical trials
This thesis demonstrates how innovative clinical trial methodology can foster pharmaceutical development. pharmaceutical development is increasingly costly and ineffective. Most time and money is directed towards late-stage clinical trials that aim to confirm the safety and efficacy of the investigated medicine. The methods discussed in this thesis help to optimize the efficiency and success-rates of these trials, which is crucial to ensure the continued arrival of new and affordable therapies. Clinical Trial Simulation (CTS) was presented as an effective technique to simulate the conduct of a trial in order to identify shortcomings in the study protocol before the trial is started. Various adaptive study designs (i.e. designs that allow for modifications of the protocol while the trial is on-going) were shown to have major potential to increase trial efficiency (i.e. reduce sample size requirements). The methods that were discussed in this thesis were shown to be statistically sound and potentially (much) more efficient than conventional approaches. Pharmaceutical developers are therefore encouraged to apply them.
Results
- Boessen R, Groenwold RH, Knol MJ, Grobbee DE, Roes KC. Classifying responders and non-responders; does it help when there is evidence of differentially responding patient groups? In: J Psychiatr Res, 2012; 46(9): 1169-73. (journal publication)
- Boessen R, Groenwold RH, Knol MJ, Grobbee DE, Roes KC. Comparing HAMD(17) and HAMD subscales on their ability to differentiate active treatment from placebo inrandomized controlled trials. In: J Affect Disord, 2013; 145(3): 363-9. (journal publication)
- Boessen R, Knol MJ, Groenwold RH, Grobbee DE, Roes KC. Increasing trial efficiency by early reallocation of placebo nonresponders in sequential parallel comparison designs: Application to antidepressant trials. In: Clin Trials, 2012; 9(5): 578-87. (journal publication)
- Methods to improve the efficiency of confirmatory clinical trials (thesis)
- Boessen R, Knol MJ, Groenwold RH, Roes KC. Validation and predictive performance assessment of clinical trial simulation models. In: Clin Pharmacol Ther, 2011; 89(4): 487,8; author reply 488. (journal publication)