Blinded sample size review for McNemar's test based on primary and surrogate endpoints

2026-08-18

AI Summary

本文针对配对二元主要和短期替代终点，开发了McNemar检验的盲样本大小重估策略，以保持I类错误率同时达到预定目标功效。

Abstract

We develop blinded sample size re-estimation strategies for McNemar's test based on paired binary primary and secondary short-term surrogate endpoints. The development is motivated by a prospective randomized clinical trial on childhood glaucoma. A conditional power expression for McNemar's test given the primary endpoint at an interim analysis is derived and complemented by a sample size re-estimation rule. We show that this procedure preserves the type I error rate while allowing the second-stage sample size to be chosen to attain a prespecified target power. In the case where for some patients only a short-term surrogate endpoint is available at interim, we introduce a surrogate-based re-estimation approach that conditions on all possible numbers of primary-endpoint discordant pairs using transition rates from the surrogate to the primary outcome. We show how these transition rates can be estimated from data on a subsample for which both surrogate and primary endpoint are available. We derive the resulting surrogate endpoint-based conditional power and sample size rule and illustrate their use with the example of the motivating trial.

Problem

• blinded sample size re-estimation
• McNemar's test
• primary endpoint
• surrogate endpoint

Innovation

• Blinded sample size re-estimation
• McNemar's test
• Surrogate endpoints
• Conditional power