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Treatment effect measures under nonproportional hazards.
Steven Snapinn1, Qi Jiang2, Chunlei Ke3
1Seattle-Quilcene Biostatistics LLC, Seattle, Washington, USA.
Pharmaceutical Statistics
|October 7, 2022
Summary
Treatment benefit measures are inconsistent under nonproportional hazards. A new generalized hazard difference captures two independent dimensions of benefit, offering a more interpretable clinical measure.
Area of Science:
- Biostatistics
- Clinical Trials
- Epidemiology
Background:
- Treatment effect measurement in time-to-event trials is complex.
- Existing measures can be inconsistent under nonproportional hazards, where survival curves may cross.
Purpose of the Study:
- Critically evaluate common treatment effect measures in clinical trials.
- Identify limitations of current measures, especially under nonproportional hazards.
- Introduce a novel measure that captures independent dimensions of treatment benefit.
Main Methods:
- Analysis of treatment effect measures under proportional and nonproportional hazards.
- Demonstration of the two independent dimensions of treatment benefit: survival rate difference and restricted mean survival time difference.
- Introduction of a generalized hazard difference, estimated by exposure-adjusted incidence rates.
Main Results:
- Commonly used measures inadequately capture both dimensions of treatment benefit.
- The generalized hazard difference effectively captures both dimensions.
- The inverse of the generalized hazard difference, the number of patient-years of follow-up (NYNT), provides an interpretable measure of clinical benefit magnitude.
Conclusions:
- Existing treatment effect measures can be unreliable under nonproportional hazards.
- A generalized hazard difference, estimated via incidence rates, offers a robust measure.
- The NYNT provides an intuitive and clinically relevant quantification of treatment benefit.
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