Box 1: Definitions of endpoints

Several terms are used to describe measurements of disease and treatment effects, such as biomarkers, surrogate markers, surrogate endpoints, intermediate endpoints, etc. We applied the definitions of the Biomarker Definitions Working group [12]. The definition of ‘functional outcome measure’ was inspired by an article on Duchenne Muscular Dystrophy [13]

Biomarker A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention

Functional outcome measure A characteristic that is measured by either a function test or a (disease) symptom score

Surrogate endpoint A biomarker or functional outcome measure that is intended to substitute for a clinical endpoint and is expected to predict clinical benefit (or harm or lack of benefit or harm). Only a small subset of biomarkers and functional outcome measures may achieve surrogate endpoint status based on epidemiological, therapeutic, pathophysiological or other scientific evidence

Clinical endpoint A characteristic or variable that reflects how a patient feels, functions or survives