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Stroke. 2016 Dec;47(12):2931-2937. Epub 2016 Nov 15.

Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations Using IMS (Interventional Management of Stroke) III Data.

Author information

1
From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.). lansberg@stanford.edu.
2
From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).

Abstract

BACKGROUND AND PURPOSE:

Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies.

METHODS:

We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design.

RESULTS:

The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%).

CONCLUSIONS:

These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern.

KEYWORDS:

adaptive trial design; endovascular techniques; stroke

PMID:
27895297
PMCID:
PMC5134921
DOI:
10.1161/STROKEAHA.116.015436
[Indexed for MEDLINE]
Free PMC Article

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