Pragmatic Trials? All Talk, No Real Progress

Pragmatic clinical trials have become one of the industry’s favorite buzzwords, but where’s the real progress? Every year, the same discussions dominate conferences, whitepapers, and executive panels—yet meaningful implementation remains elusive. The industry applauds itself for “advancing” trial design, but when it comes to execution, we’re still stuck in a cycle of overpromising and underdelivering. Despite years of discussion, regulatory frameworks remain unclear, sponsors hesitate to fully embrace these models, and real-world data is still treated as supplementary rather than a primary source of evidence. The question isn’t whether pragmatic trials have potential—the question is, why hasn’t that potential turned into reality?

The promise of pragmatic trials has existed for years, yet their widespread adoption remains elusive. Regulatory frameworks like the FDA’s Center for Clinical Trial Innovation (C3TI) were highlighted as a step forward. However, the reality is that most drug approvals still rely on traditional randomized controlled trials (RCTs). The FDA’s Project Pragmatica is a promising initiative aimed at streamlining procedures while maintaining patient safety and data integrity, yet questions remain about its scalability. Without clearer guidance and more consistent regulatory acceptance, sponsors remain hesitant to embrace pragmatic trial designs fully.

Regulatory Uncertainty and Industry Hesitation

The industry talks about integrating real-world data (RWD) into trials, yet concerns about standardization and data validation continue to delay its meaningful application. The FDA’s 2018 framework for evaluating RWE laid out expectations for how real-world data could be used in regulatory decisions, but progress has been slow. The FDA has taken steps toward incorporating real-world evidence (RWE) into regulatory decisions. In 2021, the agency approved an immunosuppressant drug to prevent lung transplant rejection based on a well-designed observational study utilizing fit-for-purpose RWD, marking a significant step toward integrating RWE into drug effectiveness evaluations. However, the agency remains cautious, emphasizing the need for robust data reliability and methodological consistency. Its 2021 guidance outlines considerations for assessing electronic health records and medical claims data for regulatory use, reinforcing that while RWE is being used more frequently, its role in approvals remains supplementary rather than primary.

Similarly, the EMA published a 2023 report detailing its regulator-led studies on RWD use between September 2021 and February 2023. Out of 61 identified RWD research topics, only 30 studies were initiated, with just 14 completed. Furthermore, 36 topics were deemed feasible based on data availability and timelines, while six were declined due to perceived limited regulatory value. The majority of these studies were descriptive cohort studies rather than robust comparative analyses, indicating that while the infrastructure for RWE is developing, it has yet to be widely accepted as a regulatory-grade evidence source.

These developments suggest that while frameworks are evolving, the practical application of RWD in regulatory contexts continues to face hurdles. Despite the optimism expressed at industry events, RWD is still not widely accepted for regulatory-grade evidence, limiting its impact.

Flexibility in Trial Design: More Talk Than Action?

Many discussions emphasize making trials more efficient through flexible protocols, site burden reduction, and digital tools. These are necessary steps, yet the reality remains that protocol complexity has only increased over the years. A report from Tufts Center for the Study of Drug Development highlights that protocol complexity has steadily risen, increasing site workload and patient burden rather than reducing them. The industry tends to point out that simplifying protocols could reduce patient burden, but without a fundamental shift in trial design philosophy, the industry’s cautious approach will continue to slow progress. Pragmatic trials require a balancing act—one that ensures flexibility while maintaining rigorous data integrity. But instead of tackling this head-on, we often hear the same high-level commitments with little evidence of real implementation.

Diversity and Inclusion: A Persistent Gap

Another recurring theme is the industry’s commitment to broadening trial access and increasing diversity. While speakers acknowledged the need for more inclusive and community-based trial sites, the reality is that most research continues to be concentrated in academic centers. Clinical trials remain largely concentrated in urban settings, with 63% of participating sites located in urban areas, 21% in suburban areas, and only 15% in rural areas. This geographic imbalance means that rural populations, who often face higher burdens of disease and healthcare access challenges, are significantly underrepresented in clinical trials. The study also found that phase 1 trials were available at 67% of urban sites but only 25% of rural sites, illustrating a major gap in access to early-phase research.

Moreover, the FDA’s 2023 Drug Trials Snapshots Summary Report reveals that White participants continue to make up the majority of clinical trial populations, with representation ranging from 60-97% across different therapeutic areas. While this indicates some diversity efforts, Black and Hispanic populations remain significantly underrepresented in key disease areas, particularly in cancer and autoimmune trials. Additionally, older adults (65+) are underrepresented in trials for neurological and inflammatory diseases. These findings suggest that while some progress has been made, clinical trials still fail to fully reflect the diversity of real-world patient populations.

These findings highlight the ongoing need for increased diversity in clinical research to ensure that medical treatments are safe and effective for all populations. Industry non-profits like TransCelerate have positioned themselves as leaders in diversity efforts, but where is the impact? While they’ve published frameworks and released collaboration tools, they have failed to produce any concrete data proving measurable improvements in trial diversity.

The reality is that diversity in clinical trials remains an ongoing issue, and TransCelerate’s efforts—like many industry-backed initiatives—have been more about optics than real change. Until organizations move beyond theoretical frameworks and actually provide transparent, measurable data on their outcomes, these conversations will remain little more than corporate PR exercises. If TransCelerate has data proving otherwise, where is it? Because from what’s publicly available, it simply doesn’t exist.

Turning Words into Action

What the industry needs now is not more discussion, but action. If pragmatic trials are to move beyond theory, we need regulatory clarity on how this data can support approvals, financial and logistical investment in community-based research, and a genuine shift toward integrating RWD meaningfully. The potential benefits—faster, more inclusive, and more relevant clinical research—are too important to be stuck in an endless cycle of industry and policy discussions. In the meantime, until real change happens, the industry should stop pretending pragmatic trials are the future—because right now, they’re just a talking point 💁.