W-12: Relationship Between Efficacy and Discontinuation Rates in Clinical Trials of Moderate to Severe Crohn’s Disease

Poster Presenter

Austin Marrazza

Student
Pennsylvania State University
United States

Objectives

The aim of this analysis is to explore the relationship of clinical efficacy to study discontinuation rates in moderate to severe Crohn’s Disease.

Method

A literature search was conducted in PubMed for all phase II and phase III clinical trials with the intent of treating moderate to severe Crohn's Disease. These studies included both completed and terminated placebo-controlled studies.

Results

Of 28 studies examined from the PubMed search twelve studies were selected for analysis that had treatment arms of at least 20 subjects per arm, Crohn’s Disease Activity Index (CDAI) remission was the primary clinical endpoint endpoint of clinical remission (CDAI Score = 150 points ), and tolerability of administration of the investigational product was not the main driver for discontinuation. Among the 12 studies that were included (amounting to 28 unique treatment arms), overall discontinuation rates, discontinuation rates due to lack of efficacy, and effect size in efficacy were examined. The data obtained was assessed using two different calculated values: A ratio of discontinuation: ((Rate of discontinuation for active treatment arm)/(Rate of discontinuation for placebo)) and A difference in efficacy: (Rate of clinical remission in active treatment – rate of clinical remission in placebo). Summary data of the 12 studies were captured where on average 27.5% (17.6% median) of subjects discontinued for any reason and 17.6% (11.6% median) of subjects discontinued due to lack of efficacy. Twenty-nine % (28.6% median) of subjects reached the CDAI endpoint (CDAI Score = 150 points from baseline). Linear regression of discontinuation (expressed as a ratio) and efficacy (expressed as a ?) revealed r = -0.803 and r = -0.669 (P < .05 for both analyses) was achieved when comparing efficacy to overall discontinuation rates and discontinuation rates due to lack of efficacy, respectively.

Conclusion

A relationship between the efficacy of a drug and discontinuations in a clinical trial has been reported in several therapeutic areas. This has not been reported in trials of moderate to severe Crohn’s Disease. These findings support a relationship between efficacy and discontinuation rates in clinical trials of moderate to severe Crohn’s Disease. A subject’s use of their own integrated assessment of benefit in deciding whether to continue taking an investigational product may be a surrogate measure of efficacy in moderate to severe Crohn’s Disease.