The asthma evidence base: a call for core outcomes in interventional trials

Abstract

Objectives

Biologic therapies are emerging as an option to treat a subset of patients with severe asthma, however no direct comparison between these agents has been conducted. Furthermore, heterogeneity of outcomes in clinical trials makes it difficult to compare these agents and traditional therapies. The extent to which this heterogeneity exists has major implications for evidence-based decisions and is yet to be fully reported. We conducted a literature search to examine outcomes currently being used in clinical trials for asthma.

Data Sources

The Cochrane Library and Clinicaltrials.gov were searched for clinical trials of asthma interventions.

Study Selections

We limited our search to phase 2 through 4 clinical trials in adults, as early-phase trials tend to have pharmacodynamic and pharmacokinetic endpoints as primary outcomes. Interventions for acute exacerbations were excluded.

Results

We identified 117 studies and subsequently identified 111 outcomes. The most prevalent outcomes were asthma control and symptom severity, FEV1, and change in ACQ scale. Twenty patient-reported outcomes instruments were identified and de-facto standard asthma outcomes and PROs were under-reported in examined literature. Existing quality of life tools did not capture the day-to-day experience or the unique treatment burden from oral corticosteroids for patient with severe asthma. Compounding the absence of trials directly comparing therapies, the significant variation we identified in outcome definitions and measurement create hurdles to effectively compare traditional and biologic therapies.

Conclusion

With the growing number of clinical trials evaluating advanced therapies such as biologics, a wide range of primary and secondary outcomes are evaluated. A core outcome set created by relevant stakeholders is needed to collectively evaluate pooled outcomes in order to allow more meaningful comparisons of asthma therapies and to incorporate the patient experience.

Keywords:

• Reviews
• Quality of Life

Declaration of interest

V. Tejwani has nothing to disclose. He is supported by a National Institutes of Health (NIH) F32 (NHLBI 1F32HL149258-01) grant.

H. Chang has nothing to disclose.

A. Tran has nothing to disclose.

R. Moloney has nothing to disclose.

S. Khatri has been an investigator in clinical trials for mepolizumab in severe asthma (GlaxoSmithKline).