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Comment & Response
June 6, 2019

Survivorship Bias in Analyses of Immune Checkpoint Inhibitor Trials

Author Affiliations
  • 1Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
JAMA Oncol. 2019;5(8):1226. doi:10.1001/jamaoncol.2019.1187

To the Editor In a retrospective analysis of 137 patients with advanced non–small cell lung cancer treated with nivolumab or pembrolizumab monotherapy, Toi et al1 observed larger progression-free survival and overall survival probabilities among 66 patients who developed immune-related adverse events (irAEs) compared with 71 who did not. It is possible that the comparison is biased. The 2 groups are compared with regard to survival from the start of treatment, but the occurrence of irAEs is obviously not determined at baseline but later during follow-up. Patients with irAEs must have survived from treatment initiation to the time of the irAE, but there is no such requirement for patients without irAEs. Toi et al1 reported a median onset of irAEs of 4.7 weeks. By design, the survival curves will be more favorable to patients with irAEs and less favorable to those without irAEs. This survivorship bias is identical to the time-to-response bias in oncology studies comparing responders and nonresponders.2-4