Abstract Non‐proportional hazards have been observed in many studies especially in immuno‐oncology clinical trials. Traditional analysis using the combined approach with log‐rank test as the significance test and Cox model for treatment effect estimation becomes questionable as this approach relies heavily on the proportional hazards assumption. Inspired by the MCP‐Mod (multiple comparisons and modeling approach) that has been widely used in dose‐finding studies, we propose a similar approach to handle non‐proportional hazards. Using this approach, efficacy signal is first established by a max‐combo test, after which hazard ratios across time will be estimated using a logically nested splines model. Simulations studies and real‐data examples are used to illustrate the use of this approach.
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