What is a Pragmatic Clinical Trial
Pragmatic Elements: An Introduction to PRECIS-2
Karen Staman, MS
Jonathan McCall, MS
Liz Wing, MA
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).
PRECIS-2 Domains (Loudon et al. 2015)
|Eligibility criteria||Who is selected to participate in the trial?
A pragmatic approach would be to include anyone with the condition of interest who is likely to be a candidate for the intervention if it were being provided in usual care for this condition.
|Recruitment||How are participants recruited into the trial?
A pragmatic approach for patient recruitment would be through usual appointments at a diverse range of clinics to increase the applicability of the trial results. (Note that with PCTs, trial participants can also be groups of care providers or health systems.)
|Setting||Where is the trial being done?
Several characteristics of the setting could affect the applicability of the results, including geography, healthcare system, country, and the socioeconomic and ethnic mix of the population. A pragmatic approach would be to do the trial in an identical setting to which you intend the results to be applied.
|Organization||What expertise and resources are needed to deliver the intervention?
A more pragmatic design would incorporate the intervention into the usual organization of care (e.g., clinical workflow) for the condition of interest, making use of no more than the existing healthcare staff and resources in that setting.
|Flexibility (delivery)||How should the intervention be delivered?
The most pragmatic approach to delivery flexibility would leave the details of how to implement the intervention up to providers, as happens in usual care. Thus, the methodology of how to deliver an intervention is not rigidly prescriptive in the protocol.
|Flexibility (adherence)||What measures are in place to ensure participants adhere to the intervention?
A pragmatic approach would allow for full flexibility in how end user recipients engage with the intervention.
|Follow-up||How closely are participants followed up?
A pragmatic design would be to have no more follow-up of recipients than would be the case in usual care. Most pragmatic would be to obtain outcome data by other means such as the EHR or other usual data to measure mortality or hospital admissions.
|Primary outcome||How relevant is it to participants?
A pragmatic approach would be to select an outcome that is of obvious importance from the perspectives of all stakeholders. For example, “an intervention that aims to reduce falls in elderly people living independently in the community should have as its primary outcome the number of falls in the elderly living independently in the community. This outcome has meaning to patients, their relatives and friends, healthcare professionals, and policymakers” (Loudon et al. 2015).
|Primary analysis||To what extent are all data included?
A pragmatic approach to analysis would be to make no special allowance for non-adherence, practice variability, etc. In other words, the pragmatic approach to the analysis would typically be an intention-to-treat analysis using all available data.
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). 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).
The following Table illustrates key characteristics and examples of interventions that are more pragmatic than explanatory.
Characteristics and Examples of PCT Elements
|Trial element||Pragmatic characteristic||Example|
|Research question||Tests whether the intervention is effective in routine clinical practice||
|Setting||Embedded in the routine care setting such as primary care, community clinics, hospital units, or health systems||
|Participants||Eligible population requires little selection beyond the clinical indication of interest||
|Intervention and comparator||Compares two or more real-world treatments using flexible protocols||
|Outcomes||Endpoints are clinically relevant to participants, funders, communities, and healthcare providers||
|Clinical importance||Purposely designed for making healthcare decisions in settings in which the intervention will be implemented||
Elements Adapted from Zwarenstein et al. 2008.
View a brief video introduction to PRECIS-2
Visit the PRECIS-2 website for more information on how to understand and use the tool
Members of the NIH Collaboratory’s Health Care Systems Interactions Core applied retrospective PRECIS-2 ratings to 5 Demonstration Projects, described in Johnson et al. Trials 2016
Johnson KE, Neta G, Dember LM, et al. 2016. Use of PRECIS ratings in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. Trials. 17:32. doi:10.1186/s13063-016-1158-y. PMID:26772801.
Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. 2015. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 350:h2147. doi:10.1136/bmj.h2147. PMID: 25956159.
Zwarenstein M, Treweek S, Gagnier JJ, et al. 2008. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. 337. doi:10.1136/bmj.a2390. PMID:19001484.