Power Considerations for Studies of Lung Function in Cystic Fibrosis

Abstract

Observational studies and clinical trials in cystic fibrosis (CF) have largely been concerned with improving long-term survival. Lung function tests, in particular FEV(1), have proven to be reliable and objective measures for monitoring the course of CF lung disease. Over several decades, the variability and average rates of FEV(1) decline have been remarkably stable. In the past decade, specific treatments and management of CF have resulted in a more gradual rate of decline, so that large numbers of patients are needed to demonstrate a significant subgroup or treatment difference. New measures are needed that detect changes before lung function decline, and that reflect more subtle changes over time. As new measurement tools are developed, FEV(1) provides a model to show how age, sex, duration, and frequency of measurement are related to variability, sample size, and power in cross-sectional or longitudinal studies. Chest radiographs are a standard tool for clinical assessment of an individual patient. However, their use in clinical trials has been limited by the lack of an objective way of measuring the elements that characterize the disease process. The CT scan offers more specific measurements relating directly to the process of lung disease in CF. Computerized algorithms can provide objective scores, but it will be an ongoing challenge to confirm the validity of candidate measures and their relationship to CF lung disease.