Patients Enrolled in Randomized Controlled Trials Do Not Represent the Inflammatory Bowel Disease Patient Population

Published:February 17, 2012DOI:

      Background & Aims

      Multiple randomized controlled trials (RCTs) have been conducted to determine therapeutic efficacy of the biological agents for the inflammatory bowel diseases (IBD). However, the external validity of findings from RCTs might be compromised by their stringent selection criteria. We investigated the proportion of patients encountered during routine clinical practice who would qualify for enrollment into a pivotal RCT of biological agents for IBD.


      We performed a retrospective cohort study of adult patients with moderate–severe IBD who presented to a tertiary referral center. Inclusion and exclusion criteria were extracted from published RCTs of biologics approved by the Food and Drug Administration and applied to the study population.


      Only 31.1% of 206 patients with IBD (34% with Crohn's disease [CD], 26% with ulcerative colitis) would have been eligible to participate in any of the selected RCTs. Patients would have been excluded because they had stricturing or penetrating CD, took high doses of steroids, had comorbidities or prior exposure to biologics, or received topical therapies. Of the trial-ineligible patients with ulcerative colitis, 23.3% had colectomies, and 31.7% received infliximab, with a 63.2% response rate. Approximately half (49.4%) of the 82 trial-ineligible patients with CD received biological therapies, with lower response rates (60%) than trial-eligible patients (89%; P = .03).


      Most patients with moderate–severe IBD evaluated in an outpatient practice would not qualify for enrollment in a pivotal RCT of biological reagents; this finding raises important questions about their therapeutic efficacy beyond the clinical trial populations. Additional evaluation of the transparency of RCT design and selection criteria is needed to determine whether trial results can be generalized to the population.


      Abbreviations used in this paper:

      ACCENT 1 (A Crohn's Disease Clinical Study Evaluating Infliximab in a New Long-Term Treatment Regimen), ACT 1 and 2 (Active Ulcerative Colitis Trials), anti-TNF (anti–tumor necrosis factor alpha), CD (Crohn's disease), CHARM (Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance), CLASSIC 1 (Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn's Disease), ENACT (Efficacy of Natalizumab as Active Crohn's Therapy), ENCORE (Efficacy of Natalizumab in Crohn's Disease Response and Remission), FDA (Food and Drug Administration), HBI (Harvey–Bradshaw Index), IBD (inflammatory bowel diseases), PRECISE1 (Pegylated Antibody Fragment Evaluation in Crohn's Disease), RALES (Randomized Aldactone Evaluation), RCT (randomized controlled trial), SONIC (Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease), UC (ulcerative colitis)
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