Abstract
IntroductionPragmatic randomized controlled trials (RCTs) mimic usual clinical practice and they are critical to inform decision-making by patients, clinicians and policy-makers in real-world settings. Pragmatic RCTs assess effectiveness of available medicines, while explanatory RCTs assess efficacy of investigational medicines. Explanatory and pragmatic are the extremes of a continuum. This debate article seeks to evaluate and provide recommendation on how to characterize pragmatic RCTs in light of the current landscape of RCTs. It is supported by findings from a PubMed search conducted in August 2017, which retrieved 615 RCTs self-labeled in their titles as “pragmatic” or “naturalistic”. We focused on 89 of these trials that assessed medicines (drugs or biologics).Discussion36% of these 89 trials were placebo-controlled, performed before licensing of the medicine, or done in a single-center. In our opinion, such RCTs overtly deviate from usual care and pragmatism. It follows, that the use of the term ‘pragmatic’ to describe them, conveys a misleading message to patients and clinicians. Furthermore, many other trials among the 615 coined as ‘pragmatic’ and assessing other types of intervention are plausibly not very pragmatic; however, this is impossible for a reader to tell without access to the full protocol and insider knowledge of the trial conduct. The degree of pragmatism should be evaluated by the trial investigators themselves using the PRECIS-2 tool, a tool that comprises 9 domains, each scored from 1 (very explanatory) to 5 (very pragmatic).ConclusionsTo allow for a more appropriate characterization of the degree of pragmatism in clinical research, submissions of RCTs to funders, research ethics committees and to peer-reviewed journals should include a PRECIS-2 tool assessment done by the trial investigators. Clarity and accuracy on the extent to which a RCT is pragmatic will help understand how much it is relevant to real-world practice.
Highlights
Pragmatic randomized controlled trials (RCTs) mimic usual clinical practice and they are critical to inform decision-making by patients, clinicians and policy-makers in real-world settings
To allow for a more appropriate characterization of the degree of pragmatism in clinical research, submissions of RCTs to funders, research ethics committees and to peer-reviewed journals should include a PRECIS-2 tool assessment done by the trial investigators
Clarity and accuracy on the extent to which a RCT is pragmatic will help understand how much it is relevant to real-world practice
Summary
Self-labeling randomized controlled trials as pragmatic Currently, it is widely accepted that explanatory and pragmatic are the extremes of a continuum [12]. RCTs on medicines before they are licensed or assessing a new indication or dosage form could hardly be pragmatic, since they have to comply with clinical trials regulations that have no resemblance to their subsequent application in routine care Such feature would affect the ‘recruitment’, ‘organisation’, ‘flexibility: delivery’, ‘flexibility: adherence’ and ‘follow-up’ PRECIS-2 domains resulting into scores of 1 or close to the explanatory extreme. Both private [13] and public [28] sponsors are expanding the use of the term pragmatic to include RCTs conducted before licensing with open-label [13] and even double-blind, placebo-controlled designs [28]. The 9 domain scores should be included on clinical trials registries – such as, for instance, clinicaltrials.gov– as part of the trial description
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