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Biometrics, 2018-06, Vol.74 (2), p.529-537
2018

Details

Autor(en) / Beteiligte
Titel
Adaptive Designs for the One-Sample Log-Rank Test
Ist Teil von
  • Biometrics, 2018-06, Vol.74 (2), p.529-537
Ort / Verlag
United States: Wiley-Blackwell
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Wiley Blackwell Single Titles
Beschreibungen/Notizen
  • Traditional designs in phase Ha cancer trials are single-arm designs with a binary outcome, for example, tumor response. In some settings, however, a time-to-event endpoint might appear more appropriate, particularly in the presence of loss to follow-up. Then the one-sample log-rank test might be the method of choice. It allows to compare the survival curve of the patients under treatment to a prespecified reference survival curve. The reference curve usually represents the expected survival under standard of the care. In this work, convergence of the one-sample log-rank statistic to Brownian motion is proven using Rebolledo's martingale central limit theorem while accounting for staggered entry times of the patients. On this basis, a confirmatory adaptive one-sample log-rank test is proposed where provision is made for data dependent sample size reassessment. The focus is to apply the inverse normal method. This is done in two different directions. The first strategy exploits the independent increments property of the one-sample log-rank statistic. The second strategy is based on the patientwise separation principle. It is shown by simulation that the proposed adaptive test might help to rescue an underpowered trial and at the same time lowers the average sample number (ASN) under the null hypothesis as compared to a single-stage fixed sample design.

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