Recommendations to Standardize the Conduct of Clinical Trials Evaluating Novel Therapies for Perianal Fistulizing Crohn's Disease.

BACKGROUND & AIMS: Perianal fistulizing Crohn's disease (PFCD) is a potentially debilitating condition with few systematically evaluated treatment options. We aimed to develop expert recommendations to standardize study design and conduct of randomized controlled trials of medical therapy for patients with PFCD.

METHODS

We utilized a RAND/UCLA appropriateness method to develop a framework for conducting randomized controlled trials of medical therapy in PFCD. An expert international panel of 15 gastroenterologists, radiologists, and colorectal surgeons rated the appropriateness of survey statements in 2 rounds of voting. Median scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 on survey statements reflected panel ratings of inappropriate, uncertain, and appropriate, respectively.

RESULTS

A total of 292 statements were rated in the final survey, of which 156 (53.4%) were considered appropriate and formed the basis for recommendations. Trial eligibility should be decided based on both clinical and radiological criteria and patients should exhibit a minimum degree of clinical disease activity at screening. The primary efficacy outcome should be either a co-primary or composite endpoint of clinical and radiological assessments depending on treatment phase (induction vs maintenance), recognizing that clinical endpoints are meaningful for patients and radiological outcomes are essential to objectively capture the burden of disease. There was uncertainty regarding definition of radiological remission, but presence of a perianal fluid collection of any size was considered inconsistent with radiologic remission.

CONCLUSIONS

These recommendations may help to standardize study design and conduct and foster clinical development of much needed therapies for this debilitating manifestation of Crohn's disease.