In the study by Martín-Broto and colleagues (1) on biomarkers in patients with soft-tissue sarcomas (STS) treated with doxorubicin plus olaratumab, patients received their first cycle of single-agent olaratumab, which was not in the previously published regimen (2), and only patients with potentially resectable disease were included. Both decisions conflict with the acknowledgment of two confounding effects of small randomized trials with significant crossover: fluctuations in type I error due to random inequalities in the distribution of prognostic variables at baseline (3) and the postrandomization bias associated with the crossover effect (4).

The most frequent bias of the crossover of a very effective experimental agent to the control arm is the obscuring of the overall survival (OS) benefit in the experimental arm (increase in type II error). When the experimental agent is ineffective, the crossover artificially inflates the benefit in OS (increase...

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