Indirect comparisons of time-to-event outcomes using single-arm studies in health technology assessment (Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma)

Lead Investigator: Nahid Sultana, University of Sheffield
Title of Proposal Research: Indirect comparisons of time-to-event outcomes using single-arm studies in health technology assessment (Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma)
Vivli Data Request: 7758
Funding Source: The PhD is jointly funded by University of Sheffield and GlaxoSmithKline(GSK)
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Asthma is a common, chronic disorder of reversible airway obstruction caused by a triad of airway inflammation, bronchial smooth muscle contraction and increased airway secretions. Asthma is a major noncommunicable disease and affected an estimated 262 million people in 2019 and caused 461000 deaths. While there have been huge advances in the control of chronic childhood asthma, during the viral season, acute exacerbations are a common phenomenon. Though the mortality rate is low with acute asthma but the condition is so frequent that it causes a very high health care burden.

Asthma is associated with type 2 powerful pro-inflammatory cytokine interleukin-5 which is produced in the body tissues and is responsible of release of eosinophils in the bone marrow. Eosinophils are white blood cells that fight infection by causing swelling but too much swelling can cause problems, and this causes eosinophilic airway inflammation. Mepolizumab, a humanized monoclonal antibody, works against interleukin-5, reduces the number of eosinophils in both sputum and blood and in the need for treatment with systemic glucocorticoids. Systemic corticosteroids help to get relief of asthma symptoms by controlling inflammation in the airways of the lungs.

The DREAM clinical trial compared mepolizumab with placebo and tested the hypothesis that mepolizumab reduces the frequency of asthma exacerbations. The secondary aims of the trial were to assess the effects of treatment on blood and sputum eosinophil counts, asthma control, asthma-related quality of life, and forced expiratory volume in 1 second (FEV1). FEV1 is the maximum amount of air one can forcefully exhale in one second which describe the degree of airway obstruction caused by asthma. Mepolizumab was found to be an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma.

Single-arm trials are a special case of an indirect comparison comprising a prospective series of patients receiving the same treatment. They provide no direct estimate of treatment effects because of absence of comparator arm. The aim of this project is to perform two different statistical analyses (random network meta analysis and standard network meta analysis) on the data for a group of patients from the DREAM trial all received the same treatment. The results will then be compared to the complete results of the DREAM trial to see if these methods can be used to predict the comparative effectiveness of the treatment they received compared to other treatments. Random baseline network meta analysi (NMA) is a extention of a traditional NMA which could be used to estimate treatment contrast for single-arm study with a larger network of evidence.

Requested Studies:

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose Ranging Study to Determine the Effect of Mepolizumab on Exacerbation Rates in Subjects With Severe Uncontrolled Refractory Asthma
Data Contributor: GlaxoSmithKline
Study ID: NCT01000506
Sponsor ID: 112997