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Efficiency of a randomized confirmatory basket trial design constrained to control the family wise error rate by indication
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He, Linchen, Ren, Yuru, Chen, Han, Guinn, Daphne, Parashar, Deepak, Chen, Cong, Yuan, Shuai Sammy, Korostyshevskiy, Valeriy and Beckman, Robert A. (2022) Efficiency of a randomized confirmatory basket trial design constrained to control the family wise error rate by indication. Statistical Methods in Medical Research , 31 (7). pp. 1207-1223. doi:10.1177/09622802221091901
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Official URL: https://doi.org/10.1177/09622802221091901
Abstract
Basket trials pool histologic indications sharing molecular pathophysiology, improving development efficiency. Currently basket trials have been confirmatory only for exceptional therapies. Our previous randomized basket design may be generally suitable in the resource-intensive confirmatory phase, maintains high power even with modest effect sizes, and provides nearly k-fold increased efficiency for k indications, but controls false positives for the pooled result only. Since family-wise error rate by indications (FWER) may sometimes be required, we now simulate a variant of this basket design controlling FWER at 0.025k, the total FWER of k separate randomized trials. We simulated this modified design under numerous scenarios varying design parameters. Only designs controlling FWER and minimizing estimation bias were allowable. Optimal performance results when k=3,4. We report efficiency (expected # true positives/expected sample size) relative to k parallel studies, at 90% power (“uncorrected”) or at the power achieved in the basket trial (“corrected”, because conventional designs could also increase efficiency by sacrificing power). Efficiency and power (percentage active indications identified) improve with higher percentage of initial indications active. Up to 92% uncorrected and 38% corrected efficiency improvement is possible.
Even under FWER control, randomized confirmatory basket trials substantially improve development efficiency. Initial indication selection is critical.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QA Mathematics R Medicine > RM Therapeutics. Pharmacology R Medicine > RZ Other systems of medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cancer -- Molecular aspects , Medicine -- Research -- Cost effectiveness, Medicine -- Research -- Statistical methods, Clinical trials , Clinical trials -- Statistical methods | ||||||||
| Journal or Publication Title: | Statistical Methods in Medical Research | ||||||||
| Publisher: | Sage Publications Ltd. | ||||||||
| ISSN: | 0962-2802 | ||||||||
| Official Date: | 1 July 2022 | ||||||||
| Dates: |
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| Volume: | 31 | ||||||||
| Number: | 7 | ||||||||
| Page Range: | pp. 1207-1223 | ||||||||
| DOI: | 10.1177/09622802221091901 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Reuse Statement (publisher, data, author rights): | Posted ahead of print. He, Linchen, Ren, Yuru, Chen, Han, Guinn, Daphne, Parashar, D., Chen, Cong, Yuan, Shuai Sammy, Korostyshevskiy, Valeriy and Beckman, Robert A. (2021) Efficiency of a randomized confirmatory basket trial design constrained to control the family wise error rate by indication. Statistical Methods in Medical Research . (In Press) Copyright © 2022 (Copyright Holder). Reprinted by permission of SAGE Publications. DOI: [DOI] Users who receive access to an article through a repository are reminded that the article is protected by copyright and reuse is restricted to non-commercial and no derivative uses. | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| Copyright Holders: | Linchen He, Yuru Ren, Han Chen, Daphne Guinn, Deepak Parashar, Cong Chen, Shuai Sammy Yuan, Valeriy Korostyshevskiy, Robert A. Beckman | ||||||||
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