Comparative effectiveness of Umeclidinium + Vilanterol versus Indacaterol + Glycopyrronium bromide assessing exacerbation frequency, costs and resource-use among patients with Chronic Obstructive Pulmonary Disease in a UK real-world primary care setting

Date of Approval
Application Number
Technical Summary

Aim: To compare real-world effectiveness of Umeclidinium/Vilanterol (UMEC/VI) versus Indacaterol/ Glycopyrronium bromide (IND/GLY) on acute exacerbations of COPD (AECOPD) and health care resource utilisation (HCRU) and direct medical costs, among a General Practice (GP) chronic obstructive pulmonary disease (COPD) cohort in England.
Objectives: To compare i) rate of moderate-to-severe AECOPD (also moderate and severe separately); ii) time to first on treatment AECOPD (moderate-to-severe, moderate, severe) and iii) all-cause and COPD-related HCRU/ direct medical costs, among COPD patients newly initiating dual therapy with single inhaler UMEC/VI versus IND/GLY. Uptake of triple therapy will also be described (proportion of patients receiving single- or multiple-inhaler triple therapy [(SITT or MITT]) and time until triple therapy initiation).
Primary exposures: Single inhaler UMEC/VI or IND/GLY initiation.
Primary outcomes: Rate of moderate-to-severe AECOPDs
Methods: A new-user, active comparator, retrospective cohort study using inverse probability of treatment weighting (IPTW) to adjust for measured confounders to assess the non-inferiority of UMEC/VI versus IND/GLY using linked CPRD Aurum and Hospital Episode Statistics (HES) data. In the event that non-inferiority is demonstrated, superiority will then be examined. The first/earliest date of dual therapy (UMEC/VI or IND/GLY) initiation between January 2015 and September 2019 will determine the index date. No minimum follow-up is required for inclusion into the study.

Data analysis: A propensity score (PS) method will be implemented to minimise potential confounding and evaluate average effects in the population. Logistic regression will generate the PS, which will be applied via IPTW. Rate of AECOPDs (events per person-year) will be compared using IPTW-weighted rate ratios (RRs) from negative binomial regression. HCRU and costs (derived via application of unit costs/tariffs) will be compared using IPTW-weighted RRs from negative binomial regression and relative rates from generalised linear models, respectively. Time-to-triple therapy will be assessed using Kaplan-Meier survival analysis and Cox proportional hazards models.

Health Outcomes to be Measured

Rate of AECOPD (moderate-to-severe, moderate, severe); time to first AECOPD (moderate-to-severe, moderate, severe); HCRU (all-cause and COPD-related); Direct medical costs (all-cause and COPD-related); proportion of patients receiving triple therapy; Time-to-triple therapy


Gema Requena - Chief Investigator - GlaxoSmithKline - UK
Victoria Banks - Corresponding Applicant - Adelphi Real World
Afisi Ismaila - Collaborator - GSK
Alexandrosz Czira - Collaborator - GSK
Catherine Castillo - Collaborator - Adelphi Real World
Eunmi Ha - Collaborator - Adelphi Real World
Jie Yeap - Collaborator - Adelphi Real World
Robert Wood - Collaborator - Adelphi Real World
Rosie Wild - Collaborator - Adelphi Real World
Theo Tritton - Collaborator - Adelphi Real World


HES Accident and Emergency;HES Admitted Patient Care;Patient Level Index of Multiple Deprivation