Efficiency of Study Designs in Diagnostic Randomized Clinical Trials

摘要

From the patients’ management perspective, a good diagnostic test should contribute to both reflecting the true disease status and improving clinical outcomes. The diagnostic randomized clinical trial is designed to combine both diagnostic tests and therapeutic interventions. Evaluation of diagnostic tests are carried out with therapeutic outcomes as the primary endpoint, rather than test accuracy. We lay out the probability framework for evaluating such trials. Two commonly referred designs –the two-arm design and the paired design– are compared in a formal statistical hypothesis testing setup and the causal connection between the two tests is identified. The paired design is shown to be more efficient than the two-arm design. The efficiency gains vary depending on the discordant rates of test results. Sample size formulas are derived for both binary and continuous endpoints. Estimation of important quantities under the paired design is derived and simulation studies are also conducted to verify the theoretical results. The method is illustrated with an example of designing a randomized study on preoperative staging of bladder cancer.