Validation of Constant Work Rate Cycling Endurance Time for Use in Chronic Obstructive Pulmonary Disease Clinical Trials.

ABSTRACT

Rationale A COPD Foundation working group sought to identify measures of exercise endurance, a meaningful aspect of physical functioning in everyday life among patients with chronic obstructive pulmonary disease (COPD) that is not fully accepted in regulatory decision making, hampering drug development. Objectives: To demonstrate, as we previously asserted (Casaburi COPD 2022;9252), that constant work rate cycling endurance time is an appropriate exercise endurance measure in patients with COPD. Methods: To validate this assertion, we assembled an integrated database of endurance time responses, including 8 bronchodilator (2,166 subjects) and 15 exercise training (3,488 subjects) studies (Casaburi COPD 2022;9520). Results: Construct validity was demonstrated 1) peak physiologic and perceptual responses were similar for constant work rate and incremental cycling; 2) after bronchodilator therapy, there were greater increases in endurance time in patients with more severe airflow limitation; 3) after exercise training, endurance time increases were similar across airflow limitation severities; and 4) there were correlations between changes in endurance time and changes in mechanistically related physiologic and perceptual variables. Test-retest reliability was demonstrated, with consistency of changes in endurance time at two time points after the intervention. Responsiveness was confirmed, with significant increases in endurance time after active (but not placebo) bronchodilator therapy, with greater increases seen with more severe airflow limitation and after exercise training. On the basis of regression analysis using multiple anchor variables, the minimum important difference for endurance time increase is estimated to be approximately 1 minute. Conclusions: Constant work rate cycling endurance time is a valid exercise endurance measure in COPD, suitable for contributing to the evaluation of treatment benefit supporting regulatory decision making and evidence-based therapeutic recommendations.