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Adjusting for treatment selection in phase II/III clinical trials with time to event data
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Khan, Josephine N., Kimani, Peter K., Glimm, Ekkehard and Stallard, Nigel (2022) Adjusting for treatment selection in phase II/III clinical trials with time to event data. Statistics in Medicine . doi:10.1002/sim.9606 ISSN 0277-6715. [ 🗎 Public]. [ (✓) hoa:511 ] (In Press)
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WRAP-adjusting-treatment-selection-phase-II-III-clinical-trials-time-event-data-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1868Kb) | Preview |
Official URL: https://doi.org/10.1002/sim.9606
Abstract
Phase II/III clinical trials are efficient two‐stage designs that test multiple experimental treatments. In stage 1, patients are allocated to the control and all experimental treatments, with the data collected from them used to select experimental treatments to continue to stage 2. Patients recruited in stage 2 are allocated to the selected treatments and the control. Combined data of stage 1 and stage 2 are used for a confirmatory phase III analysis. Appropriate analysis needs to adjust for selection bias of the stage 1 data. Point estimators exist for normally distributed outcome data. Extending these estimators to time to event data is not straightforward because treatment selection is based on correlated treatment effects and stage 1 patients who do not get events in stage 1 are followed‐up in stage 2. We have derived an approximately uniformly minimum variance conditional unbiased estimator (UMVCUE) and compared its biases and mean squared errors to existing bias adjusted estimators. In simulations, one existing bias adjusted estimator has similar properties as the practically unbiased UMVCUE while the others can have noticeable biases but they are less variable than the UMVCUE. For confirmatory phase II/III clinical trials where unbiased estimators are desired, we recommend the UMVCUE or the existing estimator with which it has similar properties.
| Item Type: | Journal Article | |||||||||
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| Subjects: | R Medicine > R Medicine (General) R Medicine > RA Public aspects 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 |
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| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Clinical trials , Clinical trials -- Statistical methods , Medical statistics , Clinical trials -- Methodology | |||||||||
| Journal or Publication Title: | Statistics in Medicine | |||||||||
| Publisher: | John Wiley & Sons Ltd. | |||||||||
| ISSN: | 0277-6715 | |||||||||
| Official Date: | 23 November 2022 | |||||||||
| Dates: |
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| DOI: | 10.1002/sim.9606 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | In Press | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 24 November 2022 | |||||||||
| Date of first compliant Open Access: | 25 November 2022 | |||||||||
| RIOXX Funder/Project Grant: |
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