Real-world Effectiveness and Cost-effectiveness of Qvar Versus FP, a US Study

Study Overview
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Brief Summary
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This study will compare the absolute and relative effectiveness and cost-effectiveness of asthma management in patients in the USA on inhaled corticosteroid (ICS) maintenance therapy as HFA-BDP (Qvar®) pressurised metered dose inhaler (pMDI) compared with fluticasone propionate (FP) pMDI. .

Detailed Description
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Current asthma guidelines 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 only a small percentage of the real-world 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 to carry out real-world observational studies to inform existing guidelines on the effectiveness of available treatments as used in every-day clinical practice in the heterogeneous asthma population. Asthma management guidelines recommend long-term, daily anti-inflammatory controller therapy to attenuate the chronic airway inflammation of persistent asthma. The choice of inhaled corticosteroid can be guided by practical considerations (e.g., cost factors) as RCTs have so far failed to identify consistent, significant differences in outcomes among the available inhaled corticosteroids, and data from observational studies are lacking. FP and HFA-BDP are the two main ICS therapies prescribed in the US for the management of asthma. FP is approximately twice as potent and efficacious, on a microgram basis, as BDP. In clinical trials, however, the extra-fine hydrofluoroalkane (HFA) formulation of BDP has demonstrated potency similar to that of FP. This is felt to be because HFA-BDP shows higher and more even lung deposition than FP, with HFA-BDP, unlike FP, having distribution to both large and small airways. Owing to similarity of effectiveness of extra-fine HFA-BDP and FP suggested by clinical trial data, and the even lung distribution afforded by the smaller HFA aerosol particles, we hypothesises that extra-fine HFA-BDP may be at least as effective as FP in real-world clinical practice. This hypothesis was supported by a retrospective database study of HFA-BDP versus FP using the UK's General Practice Research Database (GPRD). The study found significantly lower odds for achieving the composite proxy measure for asthma control with FP in both patients initiating ICS therapy (0.77, 95%CI 0.61-0.98) and stepping-up ICS therapy (0.82, 95%CI 0.44-1.52) relative to HFA-BDP. The analysis also revealed that FP was prescribed at significantly higher doses than extra-fine HFA-BDP yet had lower associated odds of achieving asthma control. In addition to significant health benefits, delivering effective asthma control is critical to reducing the substantial economic burden of asthma, with research indicating annual costs are disproportionately attributable to patients with poorly controlled disease. Recent estimates place the annual figure at 56 billion dollars ($) in the US alone, consisting of direct costs and productivity losses.It is therefore of particular importance to consider outcomes achieved in relation to costs incurred when assessing overall benefit of asthma therapies, with a cost-effectiveness analysis of HFA BDP and FP planned as part of the current study. The aim of this study is to compare the absolute and relative effectiveness and cost-effectiveness of asthma management in patients in the US on inhaled corticosteroid (ICS) maintenance therapy as extra-fine HFA-BDP (Qvar®) pressurised metered dose inhaler (pMDI) compared with fluticasone propionate (FP) pMDI to further examine the findings of the UK study, and to identify similarities or differences in effectiveness and cost-effectiveness outcomes and prescribing practice between the two countries.

Official Title
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Retrospective, Real-life Observational Evaluation of the Effectiveness and Cost-effectiveness of Extra-fine Hydrofluoroalkane (HFA) Beclometasone (BDP) Compared With Fluticasone Propionate (FP) in the Management of Asthma in a Representative Population in the United States (US)

Conditions
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Asthma

Intervention / Treatment
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* Drug: extra-fine hydrofluoroalkane beclometasone dipropionate
* Drug: Fluticasone propionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged: 5-80 years: Paediatric cohort (aged 5-11 years), and Adult cohort (aged 12-60 years) Non-smokers aged 61-80 years Evidence of asthma: a diagnostic code for asthma, (ICD 9 codes: 493xx) or ≥2 prescriptions for asthma at different points at any time Be on current asthma therapy ≥1 other asthma prescription during the outcome period Have at least one year of baseline data (prior to the IPD) and at least one year of outcome data (following the IPD). Exclusion Criteria: had been diagnosed with any chronic respiratory disease at any time other than asthma received maintenance oral steroid therapy during baseline. Updated inclusion criteria - used in the latest analysis: Aged 12-60 years (paediatrics included in original study - removed to make comparable with USA data) Evidence of asthma: a diagnostic code of asthma or ≥2 scripts for asthma in baseline year at different points in time Have definite dosing instructions Have at least 1 year of up-to-standard (UTS) baseline data before IPD Have at least 1 year of UTS outcome data after IPD. Index dates from 1998 onwards were accepted in the study. Updated exclusion criteria - used in the latest analysis: Had a diagnostic read code for chronic obstructive pulmonary disease (COPD) at any time Had a diagnostic read code for chronic respiratory disease at any time Were on maintenance oral steroid therapy at baseline

Ages Eligible for Study
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Minimum Age: 5 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 |
| --- | --- |
| IPDI: Qvar<br>ICS initiation as Qvar | Drug: extra-fine hydrofluoroalkane beclometasone dipropionate<br> <br> * Other names: Qvar®;|
| IPDI FP<br>ICS initiation as fluticasone | Drug: Fluticasone propionate<br> <br> |
| IPDA Qvar<br>ICS step-up as Qvar | Drug: extra-fine hydrofluoroalkane beclometasone dipropionate<br> <br> * Other names: Qvar®;|
| IPDA FP<br>ICS step-up as fluticasone | Drug: Fluticasone propionate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proxy Asthma Control | No recorded hospital attendance for asthma, including admission, Emergency Room (ER) attendance or Out-Patient Department (OPD) attendance, AND No prescriptions for acute courses of oral steroids, AND No GP consultations, hospital admissions or ER attendance for lower respiratory tract infections (LRTI) requiring antibiotics. | One-year outcome period | 
| Total number of asthma exacerbations and exacerbation rate ratio | Where exacerbations are defined as an occurrence of: Unscheduled hospital admissions / Emergency Room attendance for asthma, OR Use of acute courses of oral steroids | One-year outcome period | 
| Revised proxy asthma control | No recorded hospital attendance for asthma, including admission, Emergency Room (ER) attendance, out-of-hours attendance, or Out-Patient Department (OPD) attendance, AND No prescriptions for acute courses of oral steroids, AND No GP consultations, hospital admissions or ER attendance for lower respiratory tract infections (LRTI) requiring antibiotics. Average daily, prescribed dose of ≤180mcg salbutamol / albuterol or ≤500mcg terbutaline | One-year outcome period | 
| Risk Domain Asthma Control (in the subgroup of patients aged 12-60, the following additional analysis was done) | Where control is defined as the absence of the following during the one-year outcome period: Asthma-related : Hospital attendance or admission, OR A&E attendance, OR Out of hours attendance, OR Out-patient department attendance GP consultations for lower respiratory tract infection Prescriptions for acute courses of oral steroids. | One year outcome period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma control plus no additional or change in therapy | Success: defined as the absence of Exacerbation: Unscheduled hospital admissions / ER attendance for asthma, OR Acute use of oral steroids AND No consultations, hospital admissions or ER attendance for lower respiratory tract infections (LRTI) requiring antibiotics AND No change in therapeutic regimen: Increased dose of ICS, and/or Change in ICS and/or Change in delivery device, and/or Use of additional therapy as defined by: long-acting bronchodilator (LABA), theophylline, leukotriene receptor antagonists (LTRAs). | One-year outcome period | 
| Asthma control plus no additional change in therapy (where change is not driven by possible cost saving) | Exacerbation: Unscheduled hospital admissions / A&E attendance for asthma, OR Acute use of oral steroids AND No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics§ AND No change in therapeutic regimen: Increased dose of ICS, and/or Use of additional therapy as defined by: long-acting bronchodilator (LABA), theophylline, leukotriene receptor antagonists (LTRAs). | One-year outcome period | 
| Respiratory-related hospitalizations and referrals | Mean number of respiratory-related hospitalizations and referrals per patient during the outcome year | One-year outcome period | 
| Overall asthma control (Risk and Impairment) (in the subgroup of patients aged 12-60, the following additional analysis was done) | Where control is defined as the absence of the following during the one-year outcome period: Asthma-related : Hospital attendance or admission, OR A&E attendance, OR Out of hours attendance, OR Out-patient department attendance GP consultations for lower respiratory tract infection Prescriptions for acute courses of oral steroids. AND where the average prescribed daily dose of albuterol or terbutaline is ≤200mg | One year outcome period | 
| Health Economic analysis | Drug costs: Short acting beta2 agonist (SABA) costs; Fixed dose combination inhaler costs; Leukotriene receptor antagonists (LTRA) costs; Long acting beta agonists (LABA) costs; Inhaled corticosteroids (ICS) costs; Prednisolone costs; Antibiotics costs; Asthma-related drug costs (including ICS); and Asthma-related drug costs (excluding ICS). Lower respiratory primary care consultation costs; Total respiratory in-patient hospitalisation costs; Total respiratory ER attendance costs; Total respiratory out-patient attendance costs; Other Lower respiratory Medical costs. | One year outcome period | 
| Cost-effectiveness analysis | Treatment costs will be compared via differences in mean respiratory-related health care costs per patient/year. Treatment effectiveness will be compared via difference in proportion of patients controlled during the outcome period. Differences in costs and proportions of patients controlled will be displayed graphically on a cost-effectiveness plane. The four quadrants of the cost-effectiveness plane represent QVAR being: Quadrant I: more costly and more effective (a trade-off); Quadrant II: more costly and less effective (FP dominant); Quadrant III: less costly and less effective (a trade-off); and Quadrant IV: less costly and more effective (QVAR dominant) Where the point estimates indicate 'trade-off' between treatments, incremental cost-effectiveness ratio will be calculated:ICER = cQVAR - cFP/eQVAR - eFP (cQVAR and eQVAR are the cost and effectiveness of QVAR respectively and CFP and EFP are the cost and effectiveness of FP). | One year outcome period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Real-world, observational, Fluticasone propionate, Metred dose inhaler, Extra-fine hydrofluoroalkane, Asthma management, Inhaled corticosteroids, Beclomethasone dipropionate, USA