Navin Goyal (1) and Roberto Gomeni (2)
(1) Clinical Pharmacology-Modeling and Simulation, GlaxoSmithKline, PA, USA, (2) Pharmacometrica, Longcol, La Fouillade, France
Objective: Multicenter randomized clinical trials (RCTs) in depression are relatively inefficient, and fail to differentiate known effective antidepressant drug treatments from placebo in ~50% of trials. The main reason for this failure is thought to be uncontrolled placebo response. The aim of this work was to develop an adaptive approach for conducting RCTs in depression with the objective to increase the signal-to noise ratio at study-end using the band-pass filter approach.
Methods: The band-pass filter methodology has been recently proposed as a strategy for maximizing the signal to be detected in RCTs by filtering out noise occurring in form of responses outside the low and high cutoff limits of the filter [1]. In this framework, the adaptive strategy is used to identify the non-plausible placebo response trajectories generated in a given center in a clinical trial. Blinded and unblinded approaches were evaluated to classify each recruitment center on an ongoing basis as informative or non-informative. A methodology is proposed for discontinuing the enrollment in un-informative centers and to increase the patient enrollment in informative centers.
Results: Clinical trial simulation was used to demonstrate the benefit of the proposed approach as compared to the traditional study design and study conduct. The proposed adaptive approach demonstrated that the expected drug related treatment effect in a placebo-controlled RCTs can be significantly improved when data from informative recruitment centers are considered.
Conclusions: With this novel approach, the overall placebo response rate can be reduced and the signal-to-noise ratio substantially increased. Overall, such adaptive approach could markedly facilitate the process of clinical development of new compounds for the treatment of psychiatric disorders.
References:
[1] Merlo-Pich E., Alexander R.C., Fava M., and Gomeni R. A new population enrichment strategy to improve efficiency of placebo-controlled clinical trial in depression. Clin. Pharmacol. Ther., 2010 Nov;88(5):634-42.
Reference: PAGE 22 (2013) Abstr 2710 [www.page-meeting.org/?abstract=2710]
Poster: CNS