Summarizing methacholine challenges in clinical research

In clinical trials in asthma, airway reactivity is commonly assessed by performing a methacholine challenge. Airway reactivity is thought to vary in proportion to asthma severity, and methacholine causes the airways of asthma subjects to constrict, thus lowering forced expiratory volume in 1 second (FEV₁). A dose-response curve is obtained for each subject who meets standardized eligibility requirements to proceed with a methacholine challenge. When data from a methacholine challenge are used as an outcome variable in analysis, a univariate measure called the PC₂₀, the concentration of methacholine needed to produce a 20% fall in FEV₁ from baseline, is typically used to summarize the dose-response curve. Questions that arise regarding data generated from the methacholine challenge include: how to express data that do not yield a PC₂₀ value; whether PC₂₀ actually represents the best way to capture airway activity as expressed in a methacholine challenge; and whether the baseline FEV₁ is defined appropriately in calculation of PC₂₀. The impact of these issues on the statistical analysis of methacholine challenge data is described in this article. Some adjustments to the usual estimates of PC₂₀ and parametric modeling of the entire dose-response curve are proposed as alternatives that address some of the shortcomings of PC₂₀.