Randomised controlled trials in severe asthma: selection by phenotype or stereotype

Abstract

Background: Previous publications have highlighted the disparity between research trial populations and clinical practise but it is not established how this relates to randomised controlled trials (RCTs) of phenotype targeted biological therapies in severe asthma. Methods: Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and III RCTs evaluating biological therapies in severe asthma since 2000. Results: 37 RCTs evaluating 20 biological therapies were identified. Only 9.8% (median; range 3.5%–17.5%) of severe asthma patients would have been eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history exclude significant numbers of patients. 78.9% (median; range 73.2%–86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of IL-5/5R targeted therapies. Conclusion: Despite including only well characterised and optimally treated severe asthmatics under specialist care within the Wessex Severe Asthma Cohort study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.