When I give patients advice on treatment, I rely on well-designed studies to help select the medications/treatments that are most likely to be effective. It is interesting to ponder how applicable these studies are and how closely they reflect the patient population that I’m seeing. A recent article indicates that in a tertiary referral center for inflammatory bowel disease, the majority of patients would be excluded from participation in these studies (Clin Gastroenterol Hepatol 2012; 10: 1002-07).
These authors performed a retrospective cohort study of patients presenting to the Mount Sinai Medical Center between January 2008 and June 2009. For Crohn’s disease (CD) patients, the authors selected 7 published randomized control trials of biological therapy for patients with moderate-severe disease (ACCENT 1, CLASSIC 1, CHARM, PRECISE 1, ENCORE, ENACT, and SONIC). For Ulcerative Colitis (UC), they selected ACT 1 and ACT 2 trials for moderate-severe UC.
Only 31.1% of 206 patients with IBD would have been eligible to participate in any of the selected RCTs. The average age of their patients was about 35 and did not differ significantly among patients who would qualify compared to those who would not.
Among the CD patients, the inflammatory phenotype was most likely to qualify; 37 patients with inflammatory disease behavior would have been eligible. While only 54% (37 of 68) of the inflammatory phenotype would have qualified, this accounted for 86% of the total population who would have qualified (only 34% of the entire CD cohort would have been eligible for study participation).
Among the UC patients, there were no disease characteristics or demographics associated with eligibility; that is, there was a similar distribution of disease extents, Mayo scores, disease duration, gender, and age among the patients who qualified and those who did not.
Reasons for exclusion: stricturing or penetrating disease, steroid dosing, comorbities, concomitant therapies, or prior exposure to biologics.
The authors note that the results from this study mirror that from similar studies with other chronic diseases including rheumatoid arthritis, chronic obstructive pulmonary diseases, and congestive heart failure.
When the authors looked at the trial-ineligible patients, 60% had a response to biological therapy. The response rates for ineligible patients (compared to eligible patients) were lower for CD patients but not for UC patients (Figure 2 in study).
While stringent criteria for eligibility limit the external validity of the study results, these criteria are in place for multiple reasons. Less rigid selection criteria would require larger study populations, longer duration studies, and greater costs.
The issue of study applicability is even a bigger problem in pediatrics. This is primarily due to fewer high quality studies in children. As such, many clinical judgements require extrapolation from adult studies.
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