Pragmatic Implementation Trials in Cancer Prevention and Control

Pragmatic trials are a type of randomized controlled trial design that is intended to maximize external validity while maintaining internal validity and rigor. The first conceptualization of pragmatic trials was from an article from Schwartz and Lellouch in 1967, and since republished in 2009. Over the past 15 years, pragmatic trialists have further expanded on the overall operationalization of such trials for a wide range of intervention types, including behavioral interventions, multilevel interventions, and implementation trials.

Although there are many different uses and conceptualizations of the term “pragmatic trial,” one of the most well developed is that of trials along a continuum from more explanatory to more pragmatic, where elements of the trial are purposefully designed to reflect the intent and purpose of the trial and overall applicability of study findings. On one end of the continuum are explanatory trials; these are trials where the intention is to maximize internal validity while focusing less on external validity. They are often characterized by rather strict and structured components for aspects of the trial, including target population, recruitment approaches, and primary analysis, among others. The explanatory trial is meant to reflect “ideal” circumstances in which the intervention may be delivered. On the other end of the continuum are pragmatic trials; these are trials where the intention is to maximize external validity while still maintaining rigor. Pragmatic trials are often characterized by more lenient procedures and components of trials, where elements of the trial are meant to reflect “usual” contexts and populations in which and to whom the intervention would be delivered outside the context of the trial if shown to “work” in the trial. Results from pragmatic trials are meant to increase generalizability by designing the trial to mirror the situations in which the intervention would be delivered after the trial (again, pending supportive outcome data). Several tools and resource documents (see below) have been developed over the years to help design trials to match the overall intent and purpose of the trial, whether it be more pragmatic or more explanatory or somewhere between.

More recently, conceptualizations of the pragmatic-explanatory continuum have been applied to randomized controlled implementation trials. In 2021, members of the NCI Implementation Science (IS) team and developers of the PRECIS-2 tool adapted it to implementation trials. This adaptation is tailored to trials that test implementation strategies to increase the use of evidence-based practices and interventions. The tool is meant to be applied to trials where providers (e.g., nurse practitioners, public health practitioners, clinical practitioners) are the participants, settings include clinical and public health organizations where the evidence-based intervention is intended to be delivered (e.g., health departments, primary care practices, hospitals), and the trial is testing the effect of implementation strategies on increasing the use of evidence-based practices. My colleagues and I were delighted to host a workshop on pragmatic implementation trials at the 15th Annual Conference on the Science of Dissemination and Implementation in Health (2022) and have since presented on the topic to various research teams and training programs.

Our NCI IS team has also developed several funding opportunities to support the conduct of pragmatic trials. A division-wide team developed a Notice of Funding Opportunity, Pragmatic Trials across the Cancer Control Continuum (PAR-22-256), which includes pragmatic implementation trials. We also encourage the extramural community to check out an abundance of excellent resources on pragmatic trials developed by the NIH Pragmatic Trials Collaboratory.

In closing, we are encouraged to see more applications and thinking of implementation trials along an explanatory-pragmatic continuum. We look forward to seeing how the field further expands and builds upon these ideas, as it holds promise in helping to generate evidence that reflects the usual, everyday settings in which implementation strategies will help increase the use of evidence-based interventions. 

Select Resources, Tools, Articles:

• Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose.BMJ. 2015;350:h2147. Published 2015 May 8. doi:1136/bmj.h2147.
  • PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2): https://www.precis-2.org/

• Norton WE, Loudon K, Chambers DA, Zwarenstein M. Designing provider-focused implementation trials with purpose and intent: introducing the PRECIS-2-PS tool. Implement Sci. 2021;16(1):7. Published 2021 Jan 7. doi:1186/s13012-020-01075-y.

• Zwarenstein M. 'Pragmatic' and 'explanatory' attitudes to randomised trials. J R Soc Med. 2017;110(5):208-218. doi:1177/0141076817706303.

• NIH Pragmatic Trials Collaboratory: https://rethinkingclinicaltrials.org/

• NCI Funding Opportunities:
  • PAR-24-072: Pragmatic Trials across the Cancer Control Continuum (UG3/UH3 clinical trial required): https://grants.nih.gov/grants/guide/pa-files/PAR-22-256.html