Antifibrotics and Reduced Mortality in Idiopathic Pulmonary Fibrosis: Immortal Time Bias

Pirfenidone and nintedanib, antifibrotic medications approved for treating patients with mild to moderate idiopathic pulmonary fibrosis (IPF), have been shown to slow the decline in lung function and are recommended by international treatment guidelines. However, immortal time bias, which greatly exaggerates the benefit of drugs, is correctable with proper study design or data analysis. For example, immortal time bias can be avoided by using a time-dependent definition of exposure, such as with the Cox proportional hazards model with time-dependent exposure that allows a patient to move from a period of non-exposure to a period of exposure during the follow-up period. One could also use study design approaches such as the prevalent new-user design, which would match antifibrotic initiators with non-users in the disease course, thus avoiding immortal time bias. The authors of these 14 publications are urged to repeat their studies' analysis using revised approaches that avoid immortal time bias.