By Clinical Research News Staff

July 9, 2025 | The growing importance of pragmatic clinical trials in healthcare research cannot be overstated. In the most recent episode of the Scope of Things podcast, host Deborah Borfitz speaks with Bethany Kwan, director of the Dissemination & Implementation Research Core, Colorado Clinical & Translational Sciences Institute, University of Colorado Anschutz Medical Campus, and Heather Smyth, research associate with the Center for Innovative Design and Analysis in the Colorado School of Public Health. Together they explore the fundamental distinctions between traditional clinical trials and pragmatic research approaches, uncovering why this methodology is experiencing such significant growth in modern healthcare research.

Unlike conventional clinical trials that prioritize efficacy in controlled environments, pragmatic clinical trials focus on effectiveness in real-world settings. As Kwan explained, these studies exist on a continuum and involve testing interventions in actual healthcare environments with diverse patient populations. The approach requires interdisciplinary collaboration among experts in biostatistics, technology integration, implementation science, and community engagement. Contrary to some misconceptions, pragmatic trials demand even more methodological rigor than traditional trials because researchers must account for numerous variables present in real-world settings.

The recent surge in pragmatic research stems from multiple factors, including technological advancements that facilitate data collection through electronic health records and wearable devices. However, as Smyth pointed out, the fundamental driver is scientific curiosity and the desire to apply research findings to improve real-world conditions. There's a distinctive satisfaction in watching rigorous science translate into meaningful healthcare improvements. This philosophy aligns with broader healthcare goals of enhancing care quality while reducing costs and recognizes that healthcare operates as a business requiring evidence that innovations improve outcomes that matter to all stakeholders.

The design and implementation of pragmatic trials present unique challenges that require specialized knowledge and skills. No single researcher needs expertise in all areas; instead, team science becomes crucial. From data scientists and health economists to implementation specialists and clinical partners, successful pragmatic research depends on collaborative approaches. When working with data collected from electronic health records or other clinical sources not specifically designed for research purposes, researchers must carefully consider measurement quality and data limitations.

One fundamental distinction highlighted during the discussion was the shift in focus from internal validity (typical in traditional trials) to external validity (emphasized in pragmatic trials). While statisticians might initially feel uncomfortable with the reduced control in pragmatic settings, reframing these considerations as interesting design characteristics rather than limitations allows for richer interpretations of results. This approach embraces the nuance and complexity inherent in real-world healthcare delivery.

A significant strength of pragmatic trials is their ability to capture patient heterogeneity – what one expert called "the other 85%" typically excluded by strict eligibility criteria in traditional trials. This inclusivity allows researchers to investigate heterogeneity of treatment effects and determine whether interventions work differently across diverse populations. However, examining these interaction effects requires careful statistical planning, including potentially larger sample sizes than would be needed for detecting main effects alone. When statistical significance proves challenging due to sample constraints, researchers can still evaluate clinical significance through effect sizes.

Successfully implementing pragmatic trials demands exceptional project management skills and organizational planning. With large interdisciplinary teams, multiple research sites, and diverse perspectives, clear communication and role clarity become essential. Having a dedicated project manager can significantly improve execution. Additionally, researchers must anticipate inevitable changes during the study period—from EHR system updates to staff turnover—and build flexibility into their plans. The ability to pivot when unexpected challenges arise (like the COVID-19 pandemic) represents a fundamental difference between traditional and pragmatic approaches.

As healthcare continues to evolve, the value of pragmatic clinical trials in creating meaningful and sustainable improvements becomes increasingly evident. By embracing real-world complexity rather than controlling for it, these studies generate findings that can be more readily applied in actual healthcare settings, ultimately serving the needs of patients, providers, and health systems more effectively.

Show Notes 

Pragmatica-Lung trial a paradigm-shifting model 

• News release on SWOG Cancer Research Network website 

Pragmatic trial of pharmacogenomic testing in the UK 

• Article in Diagnostics World News 

Pragmatic approach for comparative clinical trials 

• Study in New England Journal of Medicine  

Improving access to cardiomyopathy trials 

• News release on the American Heart Association website 

Alzheimer's clinical trials pipeline report 

• Review article in Alzheimer’s and Dementia: Translational Research & Clinical Interventions 

Personalizing melanoma treatment 

• Article in Nature Medicine  

AI agents for clinical research 

• Article in Clinical Research News