Designing clinical trials to evaluate mucus clearance therapy

Abstract

Mucoactive therapy is meant to improve quality of life by making it easier to breathe and reducing the need for hospitalization and antibiotic therapy. There are a number of challenges when designing a clinical trial to test the effectiveness of potentially mucoactive therapy. These challenges can be categorized as understanding the mechanism of action for the intervention, understanding the disease being treated, and recognizing relevant outcomes that can be accurately measured. Dose, duration, route of administration, and effectiveness of a therapy are all influenced by mechanisms of action. Mucoactive therapy may not change sputum expectoration volume, expiratory airflow, or dyspnea sensation, although these are commonly measured. While clinically relevant outcomes are most informative, surrogate outcomes can be of value. The natural variability of the outcome measure in question in the population being studied must be known in order to design an appropriately powered study. The natural course of the disease being studied and the ability to accurately measure disease severity must be known in order to choose whether studies are conducted during periods of disease stability, at the time of an exacerbation, or immediately following successful therapy for an exacerbation. This information is also critically important in identifying an appropriate control group. These challenges can be met to advance our knowledge and to develop truly effective therapy for mucus clearance disorders.