Clinical trials in idiopathic pulmonary fibrosis: a word of caution concerning choice of outcome measures

Abstract

Idiopathic pulmonary fibrosis (IPF) is a challenging and frustrating disease for clinicians and patients confronted with this clinical entity, since it is associated with a dismal ∼3-yr median survival from the time of diagnosis 1 and an effective treatment regimen is yet to be determined. The lack of an effective treatment option has encouraged investigation of new treatment regimens, and promising agents are being investigated in several clinical trials worldwide. Despite aggressive, worldwide collaborations in pursuit of an effective regimen, significant progress is still needed to recommend a specific treatment regimen for IPF 2. While recent publications have provided insights regarding appropriate outcome measures chosen as end points for IPF clinical trials, results from these studies have either (unfortunately) been negative or merely provided positive signals and generated hypotheses that deserve to be investigated further in well-designed studies 3–6. Investigators who are involved in planning IPF studies face daunting challenges in selecting outcome measures that will appropriately allow statistical assessment of clinically meaningful effects or outcomes. Clinicians reviewing the IPF literature are confronted with equally daunting challenges in interpreting the clinical and statistical importance of these findings and applying this knowledge in the clinical care of their patients. Both the investigator and the clinician interpreting the results need to understand how IPF disease severity and progression are best measured in order to provide the most convincing and interpretable study evidence. The 2000 International Consensus statement for IPF diagnosis and treatment suggests measures with promise for measuring IPF disease extent and potential for measuring change, but it is clear that validated outcome measures were not known when the document was drafted 1. Investigators involved in the largest IPF trial conducted to date recently reported an apparent lack of appropriate IPF outcome measures 6. They reported …