Forced vital capacity as a primary end point in idiopathic pulmonary fibrosis treatment trials: making a silk purse from a sow's ear

Thorax

In treatment trials in idiopathic pulmonary fibrosis (IPF), there is an unmet need for an accurate primary end point. A European-wide consensus exists that mortality is not a practicable primary end point for the demonstration of beneficial treatment effects in IPF.1 Serial, 6-min-walk test data are confounded by factors other than progression of interstitial lung disease. Alone among other candidate variables, trends in forced vital capacity (FVC) have consistently predicted mortality in IPF2–11 and can, thus, be viewed as the best marker of chronic disease progression. FVC trends are now the preferred primary end point in IPF treatment trials, although not a proven surrogate for mortality.12

In pharmaceutical studies, FVC change is analysed as a continuous variable, or by designating thresholds for change as...