Analysis of Control Arm Quality in Randomized Clinical Trials Leading to Anticancer Drug Approval by the US Food and Drug Administration
The aim of our analysis was to evaluate the quality of control arms in RCTs leading to anticancer drug approvals by the FDA. We found that, between January 1, 2013, and July 31, 2018, FDA approval of 16 (17%) of 95 anticancer drugs for the market were based on RCTs with sub-optimal control arms. Future regulatory trials should be optimized to ensure that new anticancer agents being marketed are truly superior to what most clinicians would prescribe outside a clinical trial setting.
Most randomized clinical trials (RCTs) of novel anticancer drugs leading to marketing authorization by the US Food and Drug Administration (FDA) are designed, conducted, and funded by the biopharmaceutical industry. One potential concern with these studies is that in an effort to increase the likelihood of obtaining favorable results, the control arm of these studies may be suboptimal (“straw man” comparators).
For instance, Sharman et al note that the RESONATE-2 trial, a randomized trial of ibrutinib vs chlorambucil in CLL, relied on chlorambucil as control agent, a drug that has been repeatedly beaten by alternatives and has poor real-world use. Tao and Prasad note other examples of trials with suboptimal control arms, including an RCT comparing nivolumab with dacarbazine in metastatic melanoma that enrolled patients after ipilimumab had been demonstrated to be superior in this setting...
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