The ICS-RECODE study
Predictors of treatment REsponse to inhaled corticosteroids (ICS) in COPD:
randomised COntrolled trials individual participant Data re-Evaluation
Rationale
In selected patients with chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICS) reduce the risk of exacerbations, improve health status, pulmonary function and, possibly, survival. These benefits come at a risk of severe side effects, such as pneumonia. In clinical practice, blood eosinophils are used to identify people likely to benefit from ICS. However, the National Institute of Health and Care Excellence (NICE), after formally evaluating all available data, concluded that the overall evidence supporting the use of eosinophils or other biomarkers to guide ICS use is still weak. Hence, a clinical recommendation could not be supported, and research recommendations were issued instead.
Objective
This project addresses the important problem of more reliably identifying patients with COPD likely to benefit most from the administration of ICS, at the lowest risk of side effects. We will conduct an individual participant data (IPD) meta-analysis of randomised controlled trials (RCTs) to identify and validate predictive clinical biomarkers and predictive models of treatment response to ICS.
Data
We have identified 27 RCTs totalling >65,000 eligible participants and our data access applications for 22 of these RCTs with 55,394 eligible participants have already been approved. The remaining applications are under review.
Methods
Based on a prospective analysis plan:
- We will re-analyse data from all included trials with the aim to standardise the definition and evaluation of outcomes and covariates of interest (predictors of treatment response).
- We will conduct a two-stage IPD meta-analysis to assess the safety and efficacy of ICS for COPD, accounting for various potential prognostic factors (i.e. effect modifiers).
- We will then explore potential treatment-covariate interactions with selected covariates, aiming to identify and/or validate predictors of treatment response to ICS.
- Finally, we will develop and validate prediction models of treatment response, using both hypothesis-driven and data-driven methods. We will compare their performance characteristics in independent patient samples.
The ICS-RECODE study, leveraging high-quality data from over 20 randomised controlled trials with >55,000 participants, is set to revolutionise treatment decisions around inhaled corticosteroid use and promote personalised management for COPD.
The lead investigators:
Dr Alexander G. Mathioudakis
Prof Jørgen Vestbo
Manchester University NHS Foundation Trust
The University of Manchester