Blinded sample size recalculation in clinical trials with binary composite endpoints
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Blinded sample size recalculation in clinical trials with binary composite endpoints. / Sander, Anja; Rauch, Geraldine; Kieser, Meinhard.
In: J BIOPHARM STAT, Vol. 27, No. 4, 2017, p. 705-715.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Blinded sample size recalculation in clinical trials with binary composite endpoints
AU - Sander, Anja
AU - Rauch, Geraldine
AU - Kieser, Meinhard
PY - 2017
Y1 - 2017
N2 - We consider clinical trials with a binary composite endpoint where the trial is successful when a significant result is achieved for the composite or one prespecified main component. Appropriate sample size planning is challenging in this situation, as in addition to the Type I error rate, power, and target difference the overall event rates and the correlation between the test statistics have to be defined. Reliable estimates of these quantities, however, are usually hard to obtain and therefore there is a high risk to not achieve the intended power in a fixed sample size design. In this article, we propose an internal pilot study design where the nuisance parameters are estimated in a blinded way at an interim stage and where the sample size is then revised accordingly. We investigate the characteristics of the proposed design with respect to the actual Type I error rate, power, and sample size. The application of this design is illustrated by a clinical trial example.
AB - We consider clinical trials with a binary composite endpoint where the trial is successful when a significant result is achieved for the composite or one prespecified main component. Appropriate sample size planning is challenging in this situation, as in addition to the Type I error rate, power, and target difference the overall event rates and the correlation between the test statistics have to be defined. Reliable estimates of these quantities, however, are usually hard to obtain and therefore there is a high risk to not achieve the intended power in a fixed sample size design. In this article, we propose an internal pilot study design where the nuisance parameters are estimated in a blinded way at an interim stage and where the sample size is then revised accordingly. We investigate the characteristics of the proposed design with respect to the actual Type I error rate, power, and sample size. The application of this design is illustrated by a clinical trial example.
U2 - 10.1080/10543406.2016.1198371
DO - 10.1080/10543406.2016.1198371
M3 - SCORING: Journal article
C2 - 27295402
VL - 27
SP - 705
EP - 715
JO - J BIOPHARM STAT
JF - J BIOPHARM STAT
SN - 1054-3406
IS - 4
ER -
