Table 3.

Common COPD clinical trial outcome measures and regulatory agency comments

Primary outcome measures

● Rate of (reduction in) COPD exacerbations

FDA: Historically, severity of exacerbations, delay in the occurrence of an exacerbation, and duration of exacerbations to be captured as secondary end points when reduction in exacerbations is the primary outcome

EMA: Requires supporting efficacy from secondary end points of function and symptoms or health status

● Change from baseline FEV1

FDA: Historically accepted end point with recommended serial measurements over the duration of the study to ensure that the beneficial effect is sustained over time

EMA: Additional evidence of efficacy must be demonstrated through the use of a coprimary end point, which should either be a symptom‐based or patient‐related end point

● Change from baseline SGRQ

FDA: Coprimary or secondary end point

EMA: Coprimary end point with lung function measurements

Secondary outcome measures

● Change from baseline FVC

● Change in symptom‐based or patient‐related end points; examples time to first COPD exacerbation, change in baseline CAT, 6MWT, SGRQ, etc.

● Number of emergency visits

● Number of hospitalizations

● Number of subjects with TEAEs and/or SAEs

● All‐cause mortality or time to all‐cause mortality

EMA: Should be considered a relevant safety end point

Refer to FDA35 and EMA40 guidance documents for details.

6MWT, 6‐minute walk test; CAT, COPD Assessment Test; COPD, chronic obstructive pulmonary disease; EMA, European Medicines Agency; FDA, US Food and Drug Administration; FEV₁, forced expiratory volumes in 1 second; FVC, forced vital capacity; SAEs, serious adverse events; SGRQ, St. George's Respiratory Questionnaire; TEAEs, treatment‐emergent adverse events.