Increasing the efficiency of clinical trials in neurodegenerative disorders using group sequential trial designs

Journal of Clinical Epidemiology
Ruben P A van EijkLeonard H van den Berg

Abstract

Clinical trials in neurodegenerative disorders are facing high futility rates and rising development costs. We aim to review and exemplify the value of group sequential trial designs (i.e., designs with one or more prospectively planned interim analyses) within the field of amyotrophic lateral sclerosis. We reviewed the literature to identify sequentially conducted trials. Subsequently, we reanalyzed the dexpramipexole trial (EMPOWER), a classically designed and conducted trial involving 942 participants, by sequentially monitoring the functional questionnaire and survival endpoint. Finally, we simulated the performance of the sequential methodology under different treatment effects. Only six (12%) randomized, placebo-controlled trials incorporated stopping rules for both futility and superiority. Despite its high enrollment rate, sequential reanalysis of the EMPOWER study reduced the total trial duration with 140 days (23.4%, 95% confidence interval [CI] 13.2-34.4%), the number of follow-ups with 2,688 visits (23.6%, 95% CI 11.3-38.6%), and the total drug exposure time with 73,377 days (20.6%, 95% CI 9.8-35.9%). The functional questionnaire considerably increased the heterogeneity in the test statistics, which may negatively a...Continue Reading

Citations

Oct 19, 2019·The Pharmacogenomics Journal·Ruben P A van EijkMichael A van Es
Oct 31, 2019·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Ruben P A van Eijk, Angela Genge
Nov 6, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Pavan A VaswaniNabila Dahodwala
Jul 29, 2021·Neurology·Ruben P A van EijkLeonard H van den Berg

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