Cancer immunotherapy trial design with long-term survivors

Xue Ding, Jianrong Wu

Research output: Contribution to journalArticlepeer-review


Cancer immunotherapy often reflects the improvement in both short-term risk reduction and long-term survival. In this scenario, a mixture cure model can be used for the trial design. However, the hazard functions based on the mixture cure model between two groups will ultimately crossover. Thus, the conventional assumption of proportional hazards may be violated and study design using standard log-rank test (LRT) could lose power if the main interest is to detect the improvement of long-term survival. In this paper, we propose a change sign weighted LRT for the trial design. We derived a sample size formula for the weighted LRT, which can be used for designing cancer immunotherapy trials to detect both short-term risk reduction and long-term survival. Simulation studies are conducted to compare the efficiency between the standard LRT and the change sign weighted LRT.

Original languageEnglish
Pages (from-to)117-128
Number of pages12
JournalPharmaceutical Statistics
Issue number1
StatePublished - Jan 1 2021

Bibliographical note

Funding Information:
We thank the referees for their many constructive comments that have lead to significant improvements in the article. This research was supported by the Biostatistics and Bioinformatics Shared Resource Facility of the University of Kentucky Markey Cancer Center and National Cancer Institute (NCI) Cancer Center Support Grant (P30CA177558).

Publisher Copyright:
© 2020 John Wiley & Sons Ltd


  • clinical trial
  • crossing hazards
  • mixture cure model
  • sample size calculation
  • weighted log-rank test

ASJC Scopus subject areas

  • Statistics and Probability
  • Pharmacology
  • Pharmacology (medical)


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