title: Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials.
abstract: Definitive evidence of clinical efficacy in a Phase 3 trial is best shown by a beneficial impact on a clinically meaningful endpoint-that is, an endpoint that directly measures how a patient feels (symptoms), functions (the ability to perform activities in daily life), or survives. In idiopathic pulmonary fibrosis (IPF), we believe the endpoints that best meet these criteria are all-cause mortality and all-cause nonelective hospitalization. There are no validated measures of symptoms or broader constructs such as health status or functional status in IPF. A surrogate endpoint is defined as an indirect measure that is intended to substitute for a clinically meaningful endpoint. Surrogate endpoints can be appropriate outcome measures if validated. However, validation requires substantial evidence that the effect of an intervention on a clinically meaningful endpoint is reliably predicted by the effect of an intervention on the surrogate endpoint. For patients with IPF, there are currently no validated surrogate endpoints.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Campus Box 356175, University of Washington, Seattle, WA 98195, USA. graghu@u.washington.edu
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.forename: Harold R
authors.initials: HR
authors.lastname: Collard
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Flaherty
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.forename: Talmadge E
authors.initials: TE
authors.lastname: King
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
mesh_terms: D015415:Biomarkers; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods*; D006760:Hospitalization; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016040:Lung Transplantation; D019141:Respiratory System Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019141:Respiratory System Agents