Clinical Trial Risk in Chronic Obstructive Pulmonary Disease: The Effects of Drug Class and Inclusion Criteria

Abstract

Background: This study analyzed the risk of clinical trial failure in chronic obstructive pulmonary disease (COPD) drug development between 1998 and 2015. We investigated elements that influenced clinical trial risk and factors that could improve outcomes during development. Objectives: This study aims to quantify clinical trial risk for drug development in COPD and factors that affect clinical trial risk. Methods: Drugs that commenced their phase I testing in this indication from 1998 onwards were retrieved from http://www.clinicaltrials.gov. Compounds investigated had to have an endpoint relevant to the treatment of COPD and be sponsored by the pharmaceutical industry. These compounds were then analyzed based on their mechanism of action and trial inclusion criteria. Results: A total of 766 trials met our screening criteria representing 116 drugs. Of these, 9 gained approval by the US FDA during our study period. The cumulative success rate for clinical development in COPD was 13.4%. Combination therapies of long-acting β-adrenoceptor agonists (LABA)/long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)/LABA had the highest success rates at 80 and 50%, respectively. The risk-adjusted cost for drug development in COPD was USD 532.4 million. Conclusions: A 13.4% success rate in COPD implies that less than 1 in 7 compounds enrolled into clinical testing would gain FDA approval. LABA/LAMA and ICS/LABA therapies had multiple fold increases in the success rate compared to other drug classes and sizably decreased the risk-adjusted cost of drug development. Moving forward, combination therapies may offer the lowest risk of clinical failure in COPD drug development.

Clinical trial risk in leukemia: Biomarkers and trial design

“…This study has several limitations, some of which have been previously described in other research studies of similar methodology 8–13 . The databases used were extensive but not comprehensive.…”

“…Similar study methodology has been described and used to analyze drug development in other disease areas 8–13 . The phase I, II, and III clinical trials for the treatment of ALL, CLL, AML, and CML were examined.…”

“…This study is built upon clinical trial risk analysis research in other disease areas 8–13 . Previous research has reported risk in non‐Hodgkin's lymphoma, focusing specifically on diffuse large B‐cell lymphoma, follicular lymphoma, mantle cell lymphoma, and cutaneous T‐cell lymphoma 9 .…”

Review of Drug Development Guidance to Treat Chronic Obstructive Pulmonary Disease:USandEUPerspectives

“…Typically, studies examining a maintenance treatment for COPD enroll patients with moderate to very severe states of the disease, as GOLD group A patients with COPD are usually considered adequately managed with short‐acting β2‐adrenoreceptor agonist or short‐acting muscarinic antagonist as needed. Furthermore, a review of COPD phase I−III clinical studies conducted between 1998 and 2015 found a 22% greater success rate when studies included patients with GOLD 3 or 4 stages, vs. GOLD 1 or 2 stages . Currently, there is a gap in knowledge regarding how early treatment with dual bronchodilator therapy should start and clinical studies to determine whether optimizing lung function in those with the mildest COPD can alter disease progression are needed.…”