Study highlights a persistent gap between trials and treatment reality
A new study suggests that most adults receiving care for moderate-to-severe ulcerative colitis in real-world practice would not qualify for the randomized controlled trials that shape treatment evidence. The finding points to a familiar but consequential problem in medicine: therapies may be tested in populations that do not fully reflect the patients doctors actually see.
The research, published online August 4 in Crohn’s & Colitis 360, examined trial eligibility in a tertiary care setting and found that only 42.7% of 150 adult patients were eligible for at least one of seven phase 3 randomized controlled trials conducted between 2012 and 2022. Put differently, a majority of patients with moderate-to-severe ulcerative colitis in this cohort would have been excluded from the recent studies that inform clinical decisions.
That does not make the trials invalid. Randomized controlled trials remain the standard tool for establishing whether a treatment works under controlled conditions. But the study sharpens an important question for clinicians, drug developers and regulators: if large portions of the real patient population are screened out, how confidently can trial results be generalized to routine care?
How the researchers tested eligibility
The study was led by Sandra Elmasry of Mayo Clinic Arizona in Scottsdale. Researchers conducted a retrospective cohort analysis of adults with moderate-to-severe ulcerative colitis seen between January 2022 and February 2023. They then applied the inclusion and exclusion criteria from seven phase 3 randomized trials to determine how many of those patients would have qualified.
This design matters because it does not speculate about hypothetical exclusion. It takes contemporary patients from clinical practice and directly compares them against the rule sets used in major trials. The result is a practical estimate of how selective those studies may be.
The answer was stark. Fewer than half of the patients would have been trial-eligible for at least one study. That means trial populations may still be narrower than the clinical population, even after years of discussion about improving representativeness in inflammatory bowel disease research.
The main reasons patients were excluded
According to the source text, current or prior medication use was the most common exclusion factor. After that came anemia, dysplasia and disease extent. Those are not marginal details. They go to the center of what makes ulcerative colitis difficult to manage in practice.
Patients with moderate-to-severe disease are often treatment-experienced. They may have cycled through multiple therapies, developed complications or accumulated features that make their care more complex than the idealized picture of a trial participant. Excluding large numbers of those patients can help produce cleaner data, but it also narrows the window through which clinicians evaluate benefit and risk.
The prominence of medication history as an exclusion criterion is especially notable. In fast-evolving therapeutic areas, prior exposure is common rather than exceptional. If previous or current treatment use routinely blocks enrollment, the evidence base may systematically underrepresent people with the most realistic treatment journeys.
Anemia and dysplasia likewise reflect the complexity of actual disease burden. Their role as exclusion factors suggests that the patients included in trials may differ from the patients who most need nuanced evidence about safety, sequencing and expected response.
No major eligibility split by age or sex
The study also found no significant difference in trial eligibility based on age, gender or disease duration. That detail narrows the interpretation. The representativeness problem in this cohort was not primarily driven by basic demographic differences. Instead, it appears more closely linked to clinical characteristics and treatment history.
That is an important distinction because it shifts the policy conversation. Broadening access to trials is not just a matter of recruiting across demographic groups, though that remains important. It may also require revisiting exclusion rules that remove patients whose disease course is more typical of specialty practice.
For sponsors and investigators, the question becomes whether some criteria are serving scientific necessity or simply protecting a trial from complexity. Not every exclusion can or should be removed. Safety and interpretability matter. But when less than half of a relevant clinical cohort can qualify, the balance deserves scrutiny.
Why this matters for evidence, approvals and care
Ulcerative colitis is a chronic inflammatory bowel disease in which treatment decisions often involve tradeoffs across efficacy, side effects, prior therapy exposure and long-term disease control. Doctors rely on randomized trial data to compare options, yet they treat patients whose histories rarely fit neatly into trial templates.
That mismatch can have several consequences. It may complicate expectations about how well a therapy will work outside the study setting. It may leave clinicians with limited evidence for patients who have already used multiple drugs. And it may make payers, guideline panels and regulators overconfident in data drawn from narrower populations than the real world contains.
The study does not argue that randomized trials should be discarded. Rather, it strengthens the case for complementing them with broader enrollment strategies and stronger real-world evidence. If pivotal studies remain highly selective, then post-approval evidence becomes even more important for understanding how treatments perform across the full spectrum of patients.
It also raises a development question for future inflammatory bowel disease programs. Companies want trials that are efficient, interpretable and likely to meet endpoints. But health systems and patients need evidence that translates into practice. Those goals are not identical, and this study suggests the gap remains meaningful.
Some improvement, but not enough
The authors note that compared with results from 2012, the current findings may indicate improvement. In their wording, 42.7% eligibility shows potential progress, but there is still “considerable potential for improvement” in including a broader range of patients.
That framing is measured and useful. The problem is not static, and trial design may be moving in the right direction. But the new data indicate that progress has been incomplete. More than half of the patients in this real-world cohort still would not have made it into at least one contemporary phase 3 study.
For a disease area with expanding therapeutic choices, that is a warning sign. Precision in trial design is valuable, but so is external validity. If the evidence base is meant to guide daily care, it has to capture more of the people who actually receive that care.
The broader lesson extends beyond ulcerative colitis. Across medicine, the credibility of evidence depends not only on internal rigor but also on whether study populations resemble clinical reality. This new analysis shows that, in one important gastroenterology setting, that alignment remains incomplete.
This article is based on reporting by Medical Xpress. Read the original article.
Originally published on medicalxpress.com
