Use of conditional estimates of effect in cancer epidemiology: An application to lung cancer treatment

Background: In oncology clinical trials, there is the assumption that randomization sufficiently balances con-founding covariates and therefore average treatment effects are usually reported. This paper explores the wider benefits provided by conditioning on covariates for reasons other than mitigation of confounding. Methods: We reanalyzed the data from primary randomized controlled trials listed in two meta-analyses to explore the significance of conditioning on smoking status in terms of the effect magnitude of treatment on progression free survival in non-small cell lung cancer. Results: The reanalysis revealed that conditioning on smoking status using sub-group analyses provided the closest empiric estimate of individual treatment effect based on smoking status and significantly reduced the heterogeneity of treatment effect observed across studies. In addition, smoking status was determined to be a modifier of the effect of treatment. Conclusion: Conditioning on prognostic covariates in randomized trials in oncology helps generate the closest empiric estimates of individual treatment benefit, addresses heterogeneity due to varying covariate distributions across trials and facilitates future decision making as well as evidence synthesis. Conditioning using sub-group analyses also allows examination for effect modification in meta-analysis.