Clinical trial merging with real-world healthcare.

Pragmatic Trials: Bridging the Gap Between Research and Real-World Healthcare

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Lena Voss in Health & Wellness December 2025 • 4 min read.

"How Focusing on Clinical Reality Can Improve Healthcare Outcomes"


For nearly seventy years, randomized controlled trials (RCTs) have been the gold standard in medical research for evaluating the effectiveness of interventions. However, while RCTs excel at establishing internal validity—ensuring that the intervention itself causes the observed effect—concerns about their external validity, or generalizability to real-world clinical settings, have persisted. This has prompted a growing interest in research methodologies that better accommodate the complexities of clinical practice.

Enter pragmatic trials, also known as 'management trials.' These trials are designed with a primary focus on external validity, aiming to assess how well an intervention works in routine clinical practice. The concept isn't new; it was introduced half a century ago. Yet, its importance has only grown as researchers and healthcare professionals seek to bridge the gap between research findings and practical application.

The key is not to abandon the rigor of RCTs but to tailor the design to address specific research objectives. The PRECIS (PRagmatic Explanatory Continuum Indicator Summary) tool has been developed to help researchers align their trial design with their intended question, whether that question is primarily explanatory (focused on understanding mechanisms) or pragmatic (focused on real-world effectiveness).

Making Trials More Relevant: Key Considerations for Pragmatic Design

Clinical trial merging with real-world healthcare.

Several design choices distinguish pragmatic trials from more traditional RCTs. These choices revolve around ensuring that the trial reflects the realities of clinical practice:

One crucial aspect is the intervention contrast. Pragmatic trials prioritize comparisons that are relevant to clinical decision-making. If a standard treatment already exists, the new intervention should be compared to that standard, not to a placebo. This provides clinicians with practical information about whether the new intervention offers a meaningful improvement over existing options.

  • Intervention Contrast: Compare new interventions to existing standards of care, not just placebos.
  • Clinical Spectrum: Ensure the trial includes a diverse patient population that reflects the range of patients seen in clinical practice.
  • Patient-Centered Outcomes: Focus on outcomes that are meaningful to patients, such as pain relief, functional status, and quality of life.
  • Real-World Settings: Conduct trials in typical clinical settings to capture the complexities of routine care.
  • Data Collection: Integrate data collection into routine clinical workflows to minimize disruption and improve data quality.
Another important consideration is blinding. Many non-drug interventions cannot be easily blinded. In these cases, researchers need to implement strategies to minimize observation bias and contamination. This might involve separating the roles of treatment assignment and observation or using alternative consent and randomization procedures that are ethically acceptable.

The Future of Clinical Trials: A Shift Towards Real-World Impact

The move towards pragmatic trials represents a significant shift in clinical research. By prioritizing external validity and real-world applicability, these trials can generate evidence that is more directly relevant to clinical decision-making and patient care.

However, designing and conducting pragmatic trials requires careful consideration of several factors, including the intervention contrast, the clinical spectrum, the outcomes of interest, and the statistical analysis. Researchers need to make deliberate choices that align with the goal of producing evidence that is both rigorous and relevant.

As the healthcare landscape continues to evolve, pragmatic trials will play an increasingly important role in ensuring that medical interventions are effective, efficient, and patient-centered. The 'Pragmatic trials and real world evidence' series highlights the importance of integrating design options with practice, therefore this effort will push forward clinical research.

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Everything You Need To Know

1

What are pragmatic trials and how do they differ from traditional clinical research?

Pragmatic trials, also known as 'management trials,' focus on how well an intervention works in routine clinical practice. Unlike traditional randomized controlled trials (RCTs) that prioritize internal validity, pragmatic trials emphasize external validity, assessing the intervention's effectiveness in real-world conditions. This involves tailoring the trial design to reflect the complexities of actual clinical settings and patient populations.

2

How does the PRECIS tool aid in the design of pragmatic trials?

The PRECIS (PRagmatic Explanatory Continuum Indicator Summary) tool helps researchers align their trial design with their research objectives. It aids in determining whether the trial should primarily focus on explanatory aspects (understanding mechanisms) or pragmatic aspects (real-world effectiveness). By using PRECIS, researchers can make informed decisions about trial design elements to ensure the study effectively addresses its intended purpose.

3

What design choices set pragmatic trials apart from traditional randomized controlled trials (RCTs)?

Pragmatic trials differ from traditional randomized controlled trials (RCTs) in several key design choices. Pragmatic trials prioritize intervention contrasts that are relevant to clinical decision-making, comparing new interventions to existing standards of care rather than placebos. They also ensure the trial includes a diverse patient population and focus on patient-centered outcomes like pain relief and quality of life. Furthermore, pragmatic trials are conducted in typical clinical settings, integrating data collection into routine clinical workflows.

4

How do pragmatic trials address the challenges of blinding and bias, especially with non-drug interventions?

In pragmatic trials, researchers minimize observation bias and contamination by separating the roles of treatment assignment and observation, especially when blinding is not feasible for non-drug interventions. Alternative consent and randomization procedures are also used to maintain ethical standards while ensuring the integrity of the trial. These strategies are crucial for ensuring that the results accurately reflect the intervention's effect in a real-world setting.

5

What are the implications of using pragmatic trials for the future of clinical research and healthcare outcomes?

By prioritizing external validity and real-world applicability, pragmatic trials generate evidence that is more directly relevant to clinical decision-making and patient care. This shift in clinical research ensures that healthcare interventions are not only effective but also practical and beneficial in everyday clinical settings. The focus on patient-centered outcomes and diverse patient populations further enhances the impact of pragmatic trials on improving healthcare outcomes.

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