Review Articles

Robust variance estimation for covariate-adjusted unconditional treatment effect in randomized clinical trials with binary outcomes

Ting Ye ,

Department of Biostatistics, University of Washington, Seattle, WA, USA

Marlena Bannick ,

Department of Biostatistics, University of Washington, Seattle, WA, USA

Yanyao Yi ,

Global Statistical Sciences, Eli Lilly and Company, Indianapolis, IN, USA

Jun Shao

School of Statistics, East China Normal University, Shanghai, People's Republic of China;d Department of Statistics, University of Wisconsin, Madison, WI, USA

Pages | Received 20 Feb. 2023, Accepted 18 Apr. 2023, Published online: 28 Apr. 2023,
  • Abstract
  • Full Article
  • References
  • Citations

To improve the precision of estimation and power of testing hypothesis for an unconditional treatment effect in randomized clinical trials with binary outcomes, researchers and regulatory agencies recommend using g-computation as a reliable method of covariate adjustment. However, the practical application of g-computation is hindered by the lack of an explicit robust variance formula that can be used for different unconditional treatment effects of interest. To fill this gap, we provide explicit and robust variance estimators for g-computation estimators and demonstrate through simulations that the variance estimators can be reliably applied in practice.