Sample sizes for clinical trials using sputum eosinophils as a primary outcome

Abstract

Clinical trials do not report sputum eosinophil data in a consistent method and this makes it difficult to compare across studies and to evaluate the sample sizes estimated in these studies. The objectives of the paper are: 1) to systematically review reporting of effect size and sample calculations in randomised controlled trials using sputum eosinophil count as a primary outcome and 2) to illustrate sample size estimation under different methods of data representation using data from an effective anti-eosinophil treatment strategy (mepolizumab).Randomised controlled trials in adults (excluding allergen provocation models) of treatment of asthma and chronic obstructive pulmonary disease for the past 10 years were searched in Ovid MEDLINE and 20 studies were identified that met all the inclusion criteria. Only nine studies discussed sample size calculation.Change from baseline was used as an outcome in 11 studies and was expressed as change in absolute percentage count, percentage change from baseline or as fold changes.Assuming a minimal clinically important reduction of 15% in absolute terms, 18 subjects in each arm will be required to achieve 80% power using an ANCOVA analysis, which we recommend, to detect significance with an alpha error of 0.05. @ERSpublications Systematic review and illustration of sample size calculations in RCTs using sputum eosinophil count as a primary outcome

Why inflammatory phenotyping is necessary for successful drug evaluation in asthma and COPD

“…The spotlight is now firmly on clinical trial design in airway diseases and how to identify disease subtypes for testing new therapies. An article by DASGUPTA et al [4], in this issue of the European Respiratory Journal, addresses this issue by reporting a systematic review of the use of one biomarker, sputum eosinophils, in randomised controlled trials over the past 10 years, and assesses the implications for study design, analysis and sample size in particular.…”

“…subject selection, and secondly, in measuring the drug effect. The article by DASGUPTA et al [4] addresses the second of these issues. Their systematic literature review identified 20 randomised controlled trials in asthma and COPD over the past decade that used sputum eosinophils as an outcome measurement.…”

“…Despite these differences, the induced sputum eosinophil count appears surprisingly robust to these variations. Results can be expressed in several ways, such as post-intervention % -pre-intervention %, fold change (post-intervention %/pre-intervention %) and percentage change from baseline, and DASGUPTA et al [4] evaluate these three different methods. Percentage change from baseline appears an unstable measure.…”

“…DASGUPTA et al [4] propose a MCID of a 15% absolute change, which is a large change and may not be widely applicable. It performed well in the particular study design they evaluate, where refractory eosinophilic asthma patients undergo corticosteroid withdrawal.…”

“…Pathway specific therapies need to account for the prevalence of that pathway in the population under study, either by subject selection or by adjustment of sample size estimates. Biomarkers are an important part of this endeavour, and the work by DASGUPTA et al [4] shows the necessary analysis paradigm required to make best use of biomarkers in this area.…”