Idiopathic Pulmonary Fibrosis Clinical Trials: Evolving Concepts

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with variable rates of disease progression (Raghu et al., Am J Respir Crit Care Med 183:788–824, 2011). Development of therapeutic interventions has proven quite challenging, which, in part, reflects the complex underlying biology, the difficult nature of identifying the optimal endpoints for pivotal studies, and the varying rate of disease progression (Raghu et al., Am J Respir Crit Care Med 185:1044–8, 2012). Over the past 10 years, significant advances have occurred in the conduct of clinical trials in IPF (Luppi et al., Curr Opin Pulm Med 18:428–32, 2012). Table 20.1 enumerates published trials over this time period with characteristics of the individual studies. The advances included in these trials include the adoption of guideline-based diagnostic criteria, standard approaches to initial evaluation and characterization of study subjects, and a robust methodology to study conduct. Numerous challenges remain, however, including identifying the optimal primary endpoint(s) for late-stage development, the role of biomarkers or intermediate markers in clinical trials, defining disease progression in individual study subjects to allow study enrichment, and targeting novel pathways in future clinical trials. This chapter will describe the approach to diagnosis and characterization of study subjects, the approach to physiological assessment, and the modalities that are needed to design and conduct proof of concept (POC), early-phase, and late-phase therapeutic trials.