Challenging the status quo for therapeutic clinical trials in fibrotic interstitial lung diseases

BACKGROUND: Fibrotic interstitial lung diseases (fILDs) are chronic lung diseases with rising incidence and prevalence. Patients affected become increasingly breathless, dependent on supplementary oxygen and generally die from respiratory failure. Despite the availability of antifibrotic therapies, treatment options that can positively impact the quality of life of patients with fILD remain limited. OBJECTIVE: To review the current clinical trial landscape in fILD, and explore emerging strategies to accelerate the development of therapies that improve outcomes that are meaningful to patients. DISCUSSION: There is growing recognition that advances in clinical trial design and endpoint selection are needed to better and more quickly evaluate investigational therapies to improve outcomes for patients with this often-devastating disease. There is increasing interest in incorporating endpoints that reflect on how the patient feels, functions and survives rather than a singular focus on forced vital capacity changes, which currently is a widely accepted endpoint for clinical trials for fILD. To accelerate the development of more effective therapies for these patients, innovative approaches to fILD clinical trial designs are needed. Approaches such as biomarker-based cohort enrichment, incorporation of alternative endpoints, use of adaptive and/or platform trial designs and decentralisation of studies can enhance the efficiency of clinical trials. Furthermore, engaging and aligning key stakeholders, most importantly patients, is crucial to ensure that outcomes important to the patients are addressed in the trial design. This review examines the current status of clinical trials in fILD, highlights the limitations of traditional clinical trial design approaches and explores potential strategies to accelerate the path towards improved treatments and outcomes for patients living with fILD.