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A basket trial investigates the effects of one drug on multiple tumor indications. To discontinue potentially inactive indications early, an interim futility analysis is usually conducted for each indication individually once it reaches the pre-specified sample size. As enrollment rates vary among indications, the futility decisions for slow-enrolling indications could be made much later than other fast-enrolling indications, which could delay the overall decision for the trial significantly. To accelerate the futility decision in early-stage exploratory basket trials and potentially reallocate resources to other compounds earlier while still controlling the global type-I and type-II errors, we propose an optimal two-stage basket trial design with one aggregated futility analysis by aggregating (e.g., pooling) all indications together. The total sample size across all indications is pre-specified for the futility analysis, while the sample size per indication can be adapted to the enrollment rate. The final analysis is performed using the pruning and pooling approach (Chen et al. 2016). The design parameters are optimized by minimizing the expected total sample size under the null hypothesis, while explicitly controlling the global type-I and the type-II error rates. Simulation studies demonstrate that the proposed design has better operating characteristics than the designs with individual futility analysis (Zhou et al. 2019; Wu et al. 2021), while allowing for earlier futility decision.

The primary goal of an exploratory oncology clinical trial is to identify an effective drug for further development. To account for tumor indication selection error, multiple tumor indications are often selected for simultaneous testing in a basket trial. In this article, we propose optimal and minimax two-stage basket trial designs for exploratory clinical trials. Inactive tumor indications are pruned in stage 1 and the active tumor indications are pooled at end of stage 2 to assess overall effectiveness of the test drug. The proposed designs explicitly control the type I and type II error rates with closed-form sample size formula. They can be viewed as a natural extension of Simon's optimal and minimax two-stage designs for single arm trials to multi-arm basket trials. A simulation study shows that the proposed design method has desirable operating characteristics as compared to other commonly used design methods for exploratory basket trials.

Cardiac resynchronization therapy, which involves the placement of a pacing lead in the right atrium and in each ventricle, is effective in treating heart failure that is caused by left bundle branch block and cardiomyopathy. The left ventricular lead is usually placed into a lateral branch of the coronary sinus via the subclavian route. When the subclavian route is unavailable, insertion of a standard, passive-fixation coronary sinus lead via the femoral approach is feasible; however, the likelihood of subsequent dislodgment is high. Herein, we describe the placement of a novel, self-retaining, active-fixation coronary sinus lead--the Attain StarFix Model 4195 OTW Lead--in an elderly heart-failure patient, via the femoral approach. We believe that this is the 1st report of this procedure.