Many IBD patients not represented in clinical research
Dr. Christina Ha
A new study asserts major randomized, controlled trials (RCT) of therapies for inflammatory bowel disease (IBD) miss the mark when it comes to enrolling patients who are typical of those seen by physicians in daily practice.
The research, published in the September issue of Clinical Gastroenterology and Hepatology, which is the clinical practice journal of the American Gastroenterological Association, found most IBD patients failed to meet eligibility criteria for the trials. Ultimately, Christina Ha, MD, lead author of the study, said it was important to recognize the limitations of research findings when so many patients are excluded.
Ha, who is an assistant professor at the Meyerhoff Inflammatory Bowel Disease Center at Johns Hopkins School of Medicine, said, “The unique thing about the inflammatory bowel disease population is it is a heterogeneous group of people.” The two major illnesses recognized as IBD are Crohn’s disease and ulcerative colitis. Physicians see patients across the spectrum of age and with different disease manifestations and comorbidities.
The retrospective cohort study focused on 206 adult patients with moderate-to-severe IBD who presented to a tertiary referral facility (Mount Sinai Medical Center) for adjustment to their medical therapy over an 18-month period. Researchers found only 31.1 percent of these patients would have been eligible to participate in any of the selected RCTs of biological reagents, which raises questions about the therapeutic efficacy of the studied biologics beyond the limited clinical trial populations.
The eligibility determination was based on inclusion and exclusion criteria extracted from published RCTs of biologics approved by the Food and Drug Administration. Reasons patients would have been excluded included having stricturing or penetrating Crohn’s disease, taking high doses of steroids, having comorbidities or prior exposure to biologics, and receiving topical therapies.
When the criteria was applied to the cohort study’s presenting population, 34 percent of those with Crohn’s disease and 26 percent of those with ulcerative colitis would have been eligible to participate in at least one of the RCTs. The correlating converse is that two-thirds of Crohn’s patients and three-quarters of ulcerative colitis sufferers would not have been eligible, leading the study’s authors to wonder whether or not clinical trial findings are broadly applicable to the real world patient population.
“Our findings are certainly provocative,” Ha said. “Most of these patients would not have qualified for clinical trial enrollment, and yet they are being treated based on those clinical trial findings.”
She continued, “A lot of people look at clinical trials as the gold standard without really dissecting the methodology behind the trials.” In the case of the RTCs for IBD biologics, she continued, “We’re taking the results from this very select group of patients, and we’re trying to apply it very broadly to this very heterogeneous group.”
The problem, Ha said, is only expected to amplify. Not only is the incidence rate of IBD increasing, but also patients now are presenting with more complex and aggressive disease. She noted there are a number of theories and hypotheses behind the increase but few concrete answers. “While we’re learning much more about the etiology of inflammatory bowel disease, we still don’t understand the mechanism,” Ha said. Still, those who study IBD believe genetic factors, environment and gut bacteria all play a role in the manifestation and course of the illness.
Those turned away from many IBD trials were often excluded because they haven’t done well on current medications or have aggressive disease. “Yet,” Ha pointed out, “these are the people who probably need to be enrolled in the clinical trials the most.”
She continued, “Our study is a word of caution to those who design the trials to try to be more inclusive of the people who need the medications the most.”
Ideally, she would like to see researchers move toward much more inclusive, pragmatic trials, but she also pointed out there is much more expense in conducting such studies. “In order to detect these subtle changes, you must follow patients over a long period of time,” she noted.
In the meantime, Ha was quick to say that she doesn’t discount the knowledge gained from current RTCs, but she cautioned physicians to understand and appreciate the limitation of the findings in light of the large number of patients excluded from such research.
“While the data from randomized, controlled clinical trials are very important and should be used to help guide our clinical practice, they shouldn’t be the absolute determinant of medication choice because most of the patients we see don’t fit that clinical trial population,” she concluded.