Impact of prompt versus delayed initiation of single-inhaler triple therapy among patients with Chronic Obstructive Pulmonary Disease in England in real-world primary and secondary care settings

Date of Approval
Application Number
Technical Summary

Aim: To assess whether prompt versus delayed initiation of single inhaler triple therapy (SITT) fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) following a moderate-to-severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with differences in subsequent AECOPDs, readmission and healthcare resource utilisation (HCRU)/costs among COPD patients in England.

Objectives: To evaluate i) rate of subsequent AECOPDs (overall, moderate, severe), ii) time-to-first subsequent AECOPD, iii) all-cause/COPD-related readmissions, iv) time-to-first readmission, and v) all-cause/COPD-related HCRU/direct medical costs, among prompt versus delayed initiators of SITT FF/UMEC/VI following an AECOPD. These objectives will be repeated utilising time-to-initiation of FF/UMEC/VI as a continuous variable; the rate of subsequent AECOPDs will also be assessed in patients with prior AECOPDs but no prior triple therapy.

Primary exposure: SITT FF/UMEC/VI initiation post-AECOPD

Outcomes: Rate of subsequent AECOPDs; Time-to-first subsequent AECOPD; Readmissions; Time-to-first readmission; HCRU; Direct medical costs

Methods: A new-user retrospective cohort study using inverse probability of treatment weighting (IPTW) of COPD patients initiating SITT FF/UMEC/VI within 180 days of an AECOPD, using linked CPRD Aurum and Hospital Episode Statistics data. The first/earliest moderate-to-severe AECOPD (Nov-2017‒Mar-2019) will determine the index date. 12+ months AECOPD-free pre-index data will be required. Patients will be categorised as prompt (0-30) or delayed (31-180) initiators dependent on timing of initiation post-AECOPD.

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. Time-to-first AECOPD/readmission will be assessed using Kaplan-Meier estimates and compared using IPTW-weighted Cox proportional hazards 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 model, respectively.

Health Outcomes to be Measured

Rate of subsequent AECOPDs (overall, moderate and severe); Time-to-first subsequent AECOPD (overall, moderate, and severe); Direct medical costs (all-cause and COPD-related); HCRU (all-cause and COPD-related); Hospital readmissions (all-cause and COPD-related); Time-to-first hospital readmission (all-cause and COPD-related)


Kieran Rothnie - Chief Investigator - GlaxoSmithKline - UK
Robert Wood - Corresponding Applicant - Adelphi Real World
Afisi Ismaila - Collaborator - GSK
Alexandrosz Czira - Collaborator - GSK
Lucinda Camidge - Collaborator - Adelphi Real World
Lucy Massey - Collaborator - Adelphi Real World
Olivia Massey - Collaborator - Adelphi Real World
Shannon Millard - Collaborator - Adelphi Real World
Victoria Banks - Collaborator - Adelphi Real World


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