Improving the validity of noninterventional comparative effectiveness research by basing study design on a specified existing randomized controlled trial.

This issue of the American Journal of Epidemiology includes 3 articles (2 reporting original analyses and 1 systematic review) in which noninterventional studies used an existing randomized controlled trial (RCT) as a reference standard to inform noninterventional study design and against which to benchmark results. This commentary provides a brief background on the challenges of noninterventional comparative effectiveness research, before elaborating on (1) the potential benefits and challenges of basing noninterventional study design on a specified existing RCT and (2) the distinction between designing analysis based upon a specified existing RCT and studies based solely upon a hypothetical target trial. Finally, several recommendations for the conduct and reporting of noninterventional studies based on existing RCTs are provided. This article is part of a Special Collection on Pharmacoepidemiology.