Pragmatic trials

Many clinical trials of new healthcare interventions, especially those required to meet the requirements of regulatory authorities, are ‘explanatory’ in nature. This means that they are executed to strict protocols, including tight inclusion and exclusion criteria, tightly controlled delivery of the intervention and comparator, as well as any concomitant therapy, measures in place to ensure strict adherence to the intervention, intensive follow-up data, and a pre-specified analysis plan. The underlying purpose is that the trial should have the best chance of identifying differences in efficacy or safety. However, there is increasing concern that effectiveness in ‘real-world’ situations (routine practice) differs from that predicted from efficacy reported in such trials. This has led to increased interest in more ‘pragmatic’ trials, where many of the strict protocol elements are relaxed, and results may be more immediately generalisable to routine practice.