Real-life Effectiveness and Cost-effectiveness of Qvar Versus FP and BDP in the Management of COPD

Study Overview
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Brief Summary
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The objective of this study is to compare the effectiveness, cost-effectiveness and direct healthcare costs of managing chronic obstructive pulmonary disease (COPD) in primary care patients with evidence of COPD who either initiate inhaled corticosteroid (ICS) therapy, or have an increase in their ICS dose, as hydrofluoroalkane (HFA) beclometasone dipropionate (BDP) (hereafter Qvar®), CFC-BDP (hereafter BDP) and fluticasone propionate (FP) via pressurised metered-dose inhalers.

Detailed Description
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Current asthma guidelines in the UK are underpinned by evidence derived from randomised controlled trials (RCTs). Although RCT data are considered the gold standard, patients recruited to asthma RCTs are estimated to represent less than 10% of the UK's asthma population. The poor representation of the asthma population is due to a number of factors, such as tightly-controlled inclusion criteria for RCTs. There is, therefore, a need for more representative RCTs and real-life observational studies to inform existing guidelines and help optimise asthma outcomes. Short randomised trials have shown that Qvar is at least as effective as FP pMDI and as BDP pMDI at half the prescribed dose in patients with asthma. There is also evidence to suggest that, in adults, HFA formulation as used by Qvar (featuring BDP in solution rather than suspension) may achieve 10-fold higher deposition compared with CFC-BDP.4 Furthermore, deposition in the peripheral regions is higher compared with CFC-BDP and the fine-particle formulation also offers greater tolerance of poor co-ordination of breathing and inhaler actuation, resulting in lower oro-pharyngeal deposition compared with CFC-BDP. Evidence of the efficacy of ICS monotherapy in COPD remains mixed at this time. While Qvar and ICS monotherapy use in the treatment of COPD is currently off-label, it occurs in clinical practice in two common scenarios: before a diagnosis of COPD is made unlicensed use as monotherapy, or in combination with long-acting bronchodilators The study hypothesis, therefore, is that Qvar treatment in COPD may be associated with improved disease management and control (as assessed by effectiveness, cost-effectiveness and direct healthcare costs of managing COPD) compared with other commonly used ICS therapies, namely BPD and FP, by virtue of its improved deposition throughout the lungs and the small airways.

Official Title
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Retrospective, Real-life Evaluation of the Effectiveness, Cost-effectiveness and Direct Healthcare Costs of Qvar Pressurised Metered-dose Inhaler (pMDI) Compared With Beclometasone Dipropionate pMDI and Fluticasone pMDI in the Management of Chronic Obstructive Pulmonary Disease (COPD) in a Representative UK Primary Care Patient Population

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Extra-fine hydrofluoroalkane beclomethasone MDI
* Drug: Chlorofluorocarbon beclomethasone metered dose inhaler
* Drug: Fluticasone propionate metred dose inhaler
* Drug: Fluticasone propionate metred dose inhaler
* Drug: Hydrofluoroalkane beclomethasone metred dose inhaler
* Drug: Chlorofluorocarbon beclomethasone dipropionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥40 years at index prescription date COPD diagnosis: diagnostic code, and ≥2 prescriptions for COPD therapy in baseline year (at different points in time) For the ICS increase cohort (i.e. IPDA) ≥1 of these prescriptions must be for ICS therapy. Commence ICS therapy at any time (even if before COPD diagnosis is made) Exclusion Criteria: - A diagnostic read code for any other chronic respiratory disease (except asthma)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IPDA FP MDI<br>Patients who were on inhaled corticosteroid therapy as part of their baseline therapy (any ICS therapy) who, at an index prescription date, stepped-up ICS dose as fluticasone via metered dose inhaler | Drug: Fluticasone propionate metred dose inhaler<br>* Step-up in baseline BDP-equivalent ICS dose<br>|
| IPDA HFA-BDP MDI<br>Patients who were on inhaled corticosteroid therapy as part of their baseline therapy (any ICS therapy) who, at an index prescription date, stepped-up ICS dose as extra-fine hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler | Drug: Extra-fine hydrofluoroalkane beclomethasone MDI<br>* Step-up in baseline BDP-equivalent ICS dose<br>* Other names: Qvar®;|
| IPDA CFC-BDP MDI<br>Patients who were on inhaled corticosteroid therapy as part of their baseline therapy (any ICS therapy) who, at an index prescription date, stepped-up ICS dose as chlorofluorocarbon beclomethasone dipropionate via metered dose inhaler | Drug: Chlorofluorocarbon beclomethasone metered dose inhaler<br>* Step-up in baseline BDP-equivalent ICS dose<br>|
| IPDI CFC-BDP MDI<br>Patients who were not receiving inhaled corticosteroid therapy as part of their baseline therapy but who, at an index prescription date, initiated ICS as chlorofluorocarbon beclomethasone dipropionate via metered dose inhaler | Drug: Chlorofluorocarbon beclomethasone dipropionate<br>* Initiation of ICS therapy<br>|
| IPDI HFA-BDP MDI<br>Patients who were not receiving inhaled corticosteroid therapy as part of their baseline therapy but who, at an index prescription date, initiated ICS as hydrofluoroalkane beclomethasone dipropionate via metered dose inhaler | Drug: Hydrofluoroalkane beclomethasone metred dose inhaler<br>* Initiation of ICS therapy<br>* Other names: Qvar®;|
| IPDI FP MDI<br>Patients who were not receiving inhaled corticosteroid therapy as part of their baseline therapy but who, at an index prescription date, initiated ICS as fluticasone propionate via metered dose inhaler | Drug: Fluticasone propionate metred dose inhaler<br>* Initiation of ICS therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of exacerbations; exacerbation rate ratio; time to first after IPD | Where exacerbations are defined as: Unscheduled hospital admissions / A&E attendances:* For COPD (definite code) and Lower respiratory tract infections (LRTI) treated with antibiotics Acute use of oral steroids Antibiotics use with a lower respiratory read code within a ±5-day window | Two-year outcome period | 
| COPD treatment success | No recorded hospital attendance for COPD or respiratory related events (i.e. with a lower respiratory read code), including: Admission A&E attendance Out of hours attendance No exacerbations of COPD (definite plus possible prescriptions as defined above) No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics. | Two-year outcome period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COPD treatment success factoring in change in therapy | Defined as absence of: Exacerbations; and/or Increase in dose of inhaled steroid; and/or Change in delivery device, and/or Change in ICS Use of additional therapy not received in baseline year, split by: LABA Theophylline LTRAs. | Two-year outcome period | 
| COPD treatment success factoring in change in therapy unrelated to cost savings | Defined as absence of: Exacerbations; and/or Increase in dose of inhaled steroid; and/or Use of additional therapy not received in baseline year, split by: LABA Theophylline LTRAs. | Two-year outcome period | 
| Change in ICS dosing | Proportion of patients who: Remained on the same ICS (and/or combination therapy) throughout the outcome period Remained on the same ICS dose throughout the outcome period, but had another therapy added Received an ICS dose increase and / or therapy added to their ICS during the outcome period. | Two-year outcome period | 
| Rate of hospitalisations | Where hospitalisations are defined as Admissions and A&E coded as: lower respiratory-related, or for COPD Admissions and A&E coded as: lower respiratory-related, or for COPD admission attendance occurring within a ±7 day window of an LRTI treated with antibiotics. | Two-year outcomes | 
| SABA usage | Average SABA daily dose, categorised as: 0mcg, >0-100mcg, >100-200mcg, >200-400mcg, >400-800mcg, >800mcg. | Two-year outcome | 
| Mortality | Respiratory mortality All-cause mortality | Two-years | 
| Incidence of pneumonia | Unconfirmed (i.e. all unique patients with codes for pneumonia) AND Confirmed: chest X-ray within a month of a pneumonia diagnosis, or hospitalisation within a month of a pneumonia diagnosis | Two-year outcome | 
| Incremental cost effectiveness ratio | Difference in costs (HFA-BDP the comparator) over difference in effectiveness (using primary outcome of exacerbations) | Two-year outcome | 
| Cost of total healthcare treatment | Costs for each intervention: including ICS costs excluding ICS costs | Two-year outcome | 
| Costs for COPD treatment | Costs of COPD treatment: including ICS costs excluding ICS costs | Two-year outcome | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic obstructive pulmonary disease, inhaled corticosteroid, increase, initiate, exacerbations, treatment success