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Clinical Trials in IPF: What Are the Best Endpoints?

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Idiopathic Pulmonary Fibrosis

Part of the book series: Respiratory Medicine ((RM))

Abstract

Idiopathic pulmonary fibrosis (IPF), the most common and lethal of all chronic idiopathic interstitial pneumonias, is a disease that is rare and is still regarded as an orphan condition. Indeed, in the last decade more than 3000 patients have been enrolled in high-quality clinical trials of IPF, an impressive achievement for a rare condition. The most challenging obstacle in clinical trials of orphan drugs is the recruitment of an adequate number of patients to obtain sufficient evidence of efficacy and safety. Similarly critical, if not more so, is the choice of the appropriate primary endpoint(s). In disorders with a poor prognosis – like IPF – survival is the most logical outcome to measure the efficacy of a given drug. However, such trial design is feasible only in diseases that are fairly common and have a short survival with no treatment already approved. When a mortality study is impracticable, an alternative approach involves the use of predictors of survival.

There is a general agreement that the ideal primary endpoint should be reliable, reproducible, clinically meaningful, predictive of outcome, responsive to treatment effect, equally applicable to all patients, and easy to measure. However, none of the outcomes utilized over the last decade of clinical trials of IPF meets all these criteria. More attention is currently paid by physicians and regulators to endpoints that are meaningful to patients even on a short-term basis, including symptoms and quality of life measurements. In this chapter we carefully analyze the pros and cons of the outcomes most commonly used in pharmacological studies of IPF and suggest that the choice of the appropriate primary endpoint should balance scientific, statistical, and clinical rigor as well as clinical trial feasibility.

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Authors and Affiliations

  1. Section of Respiratory Diseases, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy

    Paolo Spagnolo & Elisabetta Cocconcelli

  2. Department of Pulmonary Medicine and National Reference Center for Rare Pulmonary Diseases, Competence Center for Pulmonary Arterial Hypertension, Louis Pradel Hospital, Hospices Civils de Lyon, Claude Bernard Lyon 1 University, Lyon, France

    Vincent Cottin

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  1. Paolo Spagnolo
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  2. Elisabetta Cocconcelli
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  3. Vincent Cottin
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Correspondence to Vincent Cottin .

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Editors and Affiliations

  1. Department of Internal Medicine, Section of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA

    Keith C. Meyer

  2. Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA

    Steven D. Nathan

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Spagnolo, P., Cocconcelli, E., Cottin, V. (2019). Clinical Trials in IPF: What Are the Best Endpoints?. In: Meyer, K., Nathan, S. (eds) Idiopathic Pulmonary Fibrosis. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-99975-3_19

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