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

A COPD Foundation working group sought to identify measures of exercise endurance, a meaningful aspect of physical functioning in everyday life in COPD, but not fully accepted in regulatory decision making, hampering drug development. To demonstrate, as we previously asserted [Casaburi COPD 2022;9:252], that constant work rate cycling endurance time is an appropriate exercise endurance measure in COPD patients. To validate this assertion, we assembled an integrated database of endurance time responses, including 8 bronchodilator (2166 subjects) and 15 exercise training studies (3488 subjects) [Casaburi COPD 2022;9:520]. Construct validity was demonstrated: (i) similar peak physiologic and perceptual responses for constant work rate and incremental cycling, (ii) following bronchodilator therapy, greater endurance time increase in patients with more severe airflow limitation, (iii) following exercise training, similar endurance time increases across airflow limitation severities, (iv) 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 post-intervention. Responsiveness was confirmed, with significant increases in endurance time following active (but not placebo) bronchodilator therapy, with greater increases seen with more severe airflow limitation, and following exercise training. Based on regression analysis using multiple anchor variables, minimum important difference for endurance time increase is estimated to be approximately 1 minute. Constant work rate cycling endurance time is a valid exercise endurance measure in COPD, suitable for contributing to evaluation of treatment benefit supporting regulatory decision-making and evidence-based therapeutic recommendations. Construct validity of constant work rate cycling endurance time was demonstrated: (i) similar peak physiologic and perceptual responses for constant work rate and incremental cycling, (ii) following bronchodilator therapy, greater endurance time increase in patients with more severe airflow limitation, (iii) following exercise training, similar endurance time increases across airflow limitation severities, (iv) 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 post-intervention. Responsiveness was confirmed, with significant increases in endurance time following active (but not placebo) bronchodilator therapy, with greater increases seen with more severe airflow limitation, and following exercise training. Based on regression analysis using multiple anchor variables, minimum important difference for endurance time increase is estimated to be approximately 1 minute. We conclude that constant work rate cycling endurance time is a valid exercise endurance measure in COPD, suitable for contributing to evaluation of treatment benefit supporting regulatory decision-making and evidence-based therapeutic recommendations.