Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials

Am J Respir Crit Care Med. 2012 May 15;185(10):1044-8. doi: 10.1164/rccm.201201-0006PP. Epub 2012 Apr 13.

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.

Publication types

  • Consensus Development Conference
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Clinical Trials, Phase III as Topic / methods*
  • Endpoint Determination / methods*
  • Hospitalization
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / mortality
  • Idiopathic Pulmonary Fibrosis / surgery
  • Lung Transplantation
  • Respiratory System Agents / therapeutic use*
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers
  • Respiratory System Agents