Estimating adjusted risk differences by multiply-imputing missing control binary potential outcomes following propensity score-matching

We describe a new method to combine propensity-score matching with regression adjustment in treatment-control studies when outcomes are binary by multiply imputing potential outcomes under control for the matched treated subjects. This enables the estimation of clinically meaningful measures of effect such as the risk difference. We used Monte Carlo simulation to explore the effect of the number of imputed potential outcomes under control for the matched treated subjects on inferences about the risk difference. We found that imputing potential outcomes under control (either single imputation or multiple imputation) resulted in a substantial reduction in bias compared with what was achieved using conventional nearest neighbor matching alone. Increasing the number of imputed potential outcomes under control resulted in more efficient estimation, with more efficient estimation of the estimated risk difference when increasing the number of the imputed potential outcomes. The greatest relative increase in efficiency was achieved by imputing five potential outcomes; once 20 outcomes under control were imputed for each matched treated subject, further improvements in efficiency were negligible. We also examined the effect of the number of these imputed potential outcomes on: (i) estimated standard errors; (ii) mean squared error; (iii) coverage of estimated confidence intervals. We illustrate the application of the method by estimating the effect on the risk of death within 1 year of prescribing beta-blockers to patients discharged from hospital with a diagnosis of heart failure.