Jornal de Ensaios Clínicos
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Abstrato

A Simulation Study to Evaluate Accuracy and Precision of Blinded Independent Central Reviews of Progression-free Survival in Cancer Clinical Trials

Walovitch R, Girardi V and Duan F

Purpose: To model the effect of accuracy and precision on hazard ratios, sample size and overall trial cost in Progression-Free Survival (PFS) trials using different Blinded Independent Review (BICR) paradigms.
Method: PFS times were simulated based on a tumor growth model using a median 180 days in the treatment arm; the control arm varied according to Hazard Ratios (HR) from 0.7-0.85. False positives were added for varying accuracy (1-False positive rate) and a log normal distribution of measurement error was used for varying precision. Local Evaluation (LE) accuracy of 70% and measurement error’s standard deviation of 0.30 were compared to different BICR paradigms with varying accuracy and precision (i.e., accuracy =70,90% & precision .30,.25,.20).
Results: Compared to LE, all BICR paradigms decreased overall trial costs by $ 0.0037 - 26.6.3×106 and sample sizes by 12-435 with effect magnitude being greatest at higher HRs, higher accuracy and lower measurement error.
Conclusion: Our study indicates that for trials with PFS based on a radiological assessment, BICR can be a cost-effective strategy by decreasing sample sizes and trial costs. More importantly, the study provides a quantitative indication of how changing accuracy and precision can alter sample size projections and trial cost.