Improving the Validity of Non-Interventional Comparative Effectiveness Research by Basing Study Design on a Specified Existing Randomised Controlled Trial.

This issue of AJE includes three articles (two reporting original analyses and one systematic review) in which non-interventional studies used an existing randomized controlled trial (RCT) as a reference standard to both inform non-interventional study design, and to benchmark results against. This commentary provides a brief background on the challenges of non-interventional comparative effectiveness research, before elaborating on (i) the potential benefits and challenges of basing non-interventional study design on a specified existing RCT, and (ii) the distinction between designing analysis based upon a specified existing RCT and studies based solely upon a hypothetical target trial. Finally, a number of recommendations for the conduct and reporting of non-interventional studies based upon existing RCTs are provided.