Article Text

Download PDFPDF
Hot of the breath: Mortality as a primary end-point in IPF treatment trials: the best is the enemy of the good
  1. Athol U Wells1,
  2. Juergen Behr2,
  3. Ulrich Costabel3,
  4. Vincent Cottin4,
  5. Venerino Poletti5,
  6. Luca Richeldi6,
  7. for the European IPF consensus group
  1. 1Department of Respiratory Medicine, Royal Brompton Hospital, London, UK
  2. 2Department of Internal Medicine III, Respiratory and Critical Care, University Hospital Bergmannsheil, Bochum, Germany
  3. 3Medical Faculty, University of Duisburg-Essen, and Ruhrlandklinik, Essen, Germany
  4. 4Service de Pneumologie, Hôpital Louis Pradel, Lyon, France
  5. 5Department of Respiratory Medicine, Pierantoni-Morgagni Hospital, Forlì, Italy
  6. 6Centre for Rare Lung Diseases, University of Modena Hospital, Modena, Italy
  1. Correspondence to Athol U Wells, C/O Emmanuel Kaye Building Manresa Road, Chelsea, London SW3 6LR, UK; athol.wells{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

The problem of the selection of accurate primary end-points for treatment studies in idiopathic pulmonary fibrosis (IPF) has recently been aired in a controversial paper from the USA.1 The limitations of current end-points are discussed and the authors conclude that all-cause mortality and all-cause nonelective hospitalisation best meet clinically meaningful end-point criteria. Much of the article is well argued and there is no quarrel with the view that current primary end-points are flawed. We also agree that all-cause mortality would, indeed, be the most clinically meaningful primary end-point and, therefore, the preferred primary end-point, were it not impractical, as discussed below. However, readers of the statement should reflect on the wise maxim that ‘the best may be the enemy of the good’. The purpose of our document is to provide a perspective on all-cause mortality as a primary end-point, endorsed by 52 European clinicians Including the authors (with one abstention), exploring the implications of the statement by Raghu and colleagues. We believe strongly that the adoption of the views of these authors by licensing bodies—with, by implication, a statistically significant mortality benefit a pre-requisite for drug registration—would set back progress in the treatment of IPF by a decade or more.

It should be acknowledged at the outset that the statement of Raghu and colleagues does not make explicit recommendations with regard to drug licensing. Indeed, the authors declare that it is not their aim to make such recommendations and their intentions in this regard should not be questioned. However, if the statement has, indeed, been widely ‘misread’, the reasons for this are clear enough. Representatives of the US Food and Drug Administration (FDA) were active participants in a forum in Bethesda, Maryland (July 2011) which gave rise to the document as a proceedings statement.1 It is widely known …

View Full Text

Linked Articles

  • Airwaves
    Andrew Bush Ian Pavord