Assessing the performance of physician's prescribing preference as an instrumental variable in comparative effectiveness research with moderate and small sample sizes: a simulation study.

This simulation study is to assess the utility of physician's prescribing preference (PPP) as an instrumental variable for moderate and smaller sample sizes. We designed a simulation study to imitate a comparative effectiveness research under different sample sizes. We compare the performance of instrumental variable (IV) and non-IV approaches using two-stage least squares (2SLS) and ordinary least squares (OLS) methods, respectively. Further, we test the performance of different forms of proxies for PPP as an IV. The percent bias of 2SLS is around approximately 20%, while the percent bias of OLS is close to 60%. The sample size is not associated with the level of bias for the PPP IV approach. Irrespective of sample size, the PPP IV approach leads to less biased estimates of treatment effectiveness than OLS adjusting for known confounding only. Particularly for smaller sample sizes, we recommend constructing PPP from long prescribing histories to improve statistical power.