Clinical trials that are considered “pragmatic” are designed to study a health intervention in a real-world setting that is similar or identical to the one in which the intervention will be implemented. PCTs thus stand in contrast to explanatory, or traditional, trials, which are usually designed to demonstrate the safety and efficacy of an intervention under highly controlled conditions and in carefully selected groups of participants.

Most clinical trials are situated somewhere along the spectrum between pragmatic and explanatory. The Pragmatic–Explanatory Continuum Indicator Summary (PRECIS; revised in 2015 as PRECIS-2) offers a framework to guide study teams to prospectively consider the pragmatic or explanatory nature of their trial across 9 domains (Loudon et al. 2015).

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Pragmatic–Explanatory Continuum

While ePCTs are designed to answer important, real-world clinical questions, tradeoffs in flexibility, adherence, and generalizability are inevitable. An ePCT may have some elements that are more pragmatic and some that are more explanatory. When planning the trial, it is essential to first ask, “What is the best trial design to answer the question of interest?” There is nothing inherently better or worse about a pragmatic versus traditional design. Rather, investigators should choose the degree of pragmatism for each element of the design (Figure) that will best answer the research question of interest. To evaluate the degree to which a trial is pragmatic, study teams are encouraged to read the detailed explanations of PRECIS-2, along with examples of how to apply the tool (Loudon et al. 2015).

PRECIS-2 Wheel Diagram

In 2016, members of the Health Care Systems Interactions Core and colleagues applied the PRECIS-2 criteria to 5 PCTs supported by the NIH Collaboratory. Each trial was found to be “highly pragmatic” across the PRECIS-2 domains, highlighting the tool’s potential usefulness in guiding decisions about study design but also revealing a number of challenges in applying it and interpreting the results (Johnson et al. 2016). As another example, during the conduct of the PROVEN NIH Collaboratory Trial, members of the study team applied the PRECIS-2 domains in a novel manner to assess how dynamic adaptations shifted implementation to either a more explanatory or a more pragmatic approach (Palmer et al. 2018).

PRECIS-2: Kirsty Loudon et al. BMJ 2015;350:bmj.h2147. Copyright 2015 by British Medical Journal Publishing Group. Used by permission.

• What would a PRECIS-2 wheel diagram look like for the trial you are developing?

The following Table illustrates key characteristics and examples of interventions that are more pragmatic than explanatory.

Characteristics and Examples of PCT Elements

Elements Adapted from Zwarenstein et al. 2008.