- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01287351
Real-world Effectiveness and Cost-effectiveness of Qvar Versus FP, a US Study (USQvarAsthma)
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Norfolk
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Cawston, Norfolk, United Kingdom, NR10 4FE
- Research in Real Life
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Asthma patients who either:
(i) Initiate ICS therapy as one of:
- HFA-BDP pMDI
- FP pMDI
OR
(ii) Step up ICS therapy as one of:
- HFA-BDP pMDI
- FP pMDI
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Retrospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
IPDI: Qvar
ICS initiation as Qvar
|
Other Names:
|
IPDI FP
ICS initiation as fluticasone
|
|
IPDA Qvar
ICS step-up as Qvar
|
Other Names:
|
IPDA FP
ICS step-up as fluticasone
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proxy Asthma Control
Time Frame: One-year outcome period
|
|
One-year outcome period
|
Total number of asthma exacerbations and exacerbation rate ratio
Time Frame: One-year outcome period
|
Where exacerbations are defined as an occurrence of:
|
One-year outcome period
|
Revised proxy asthma control
Time Frame: One-year outcome period
|
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)
Time Frame: One year outcome period
|
Where control is defined as the absence of the following during the one-year outcome period:
|
One year outcome period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Asthma control plus no additional or change in therapy
Time Frame: One-year outcome period
|
Success: defined as the absence of
|
One-year outcome period
|
Asthma control plus no additional change in therapy (where change is not driven by possible cost saving)
Time Frame: One-year outcome period
|
|
One-year outcome period
|
Respiratory-related hospitalizations and referrals
Time Frame: One-year outcome period
|
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)
Time Frame: One year outcome period
|
Where control is defined as the absence of the following during the one-year outcome period:
AND where the average prescribed daily dose of albuterol or terbutaline is ≤200mg |
One year outcome period
|
Health Economic analysis
Time Frame: One year outcome period
|
|
One year outcome period
|
Cost-effectiveness analysis
Time Frame: One year outcome period
|
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:
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
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Herland K, Akselsen JP, Skjonsberg OH, Bjermer L. How representative are clinical study patients with asthma or COPD for a larger "real life" population of patients with obstructive lung disease? Respir Med. 2005 Jan;99(1):11-9. doi: 10.1016/j.rmed.2004.03.026.
- Travers J, Marsh S, Caldwell B, Williams M, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. External validity of randomized controlled trials in COPD. Respir Med. 2007 Jun;101(6):1313-20. doi: 10.1016/j.rmed.2006.10.011. Epub 2006 Nov 17.
- Appleton SL, Adams RJ, Wilson DH, Taylor AW, Ruffin RE; North West Adelaide Cohort Health Study Team. Spirometric criteria for asthma: adding further evidence to the debate. J Allergy Clin Immunol. 2005 Nov;116(5):976-82. doi: 10.1016/j.jaci.2005.08.034.
- Aubier M, Wettenger R, Gans SJ. Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 microg day(-1)) versus HFA-fluticasone propionate (1000 microg day(-1)) in patients with asthma. Respir Med. 2001 Mar;95(3):212-20. doi: 10.1053/rmed.2000.1025.
- Fairfax A, Hall I, Spelman R. A randomized, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate. Ann Allergy Asthma Immunol. 2001 May;86(5):575-82. doi: 10.1016/S1081-1206(10)62907-9.
- Lasserson TJ, Cates CK, Jones AB, Steele EH, White J. Fluticasone versus HFA-beclomethasone dipropionate for chronic asthma in adults and children. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD005309. doi: 10.1002/14651858.CD005309.pub3.
- Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute, National Institutes of Health, 2007. (Accessed March 2008, at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.)
- British Guideline on the Management of Asthma, May 2008. 2008. (Accessed 26 June 2008, at http://www.sign.ac.uk/guidelines/fulltext/101/index.html.)
- Global Strategy for Asthma Management and Prevention, updated 2008. 2008. (Accessed at http://www.ginasthma.org.)
- Fanta CH. Asthma. N Engl J Med. 2009 Mar 5;360(10):1002-14. doi: 10.1056/NEJMra0804579. No abstract available. Erratum In: N Engl J Med. 2009 Apr 16;360(16):1685. N Engl J Med. 2009 Sep 10;361(11):1123.
- Shepherd J, Rogers G, Anderson R, Main C, Thompson-Coon J, Hartwell D, Liu Z, Loveman E, Green C, Pitt M, Stein K, Harris P, Frampton GK, Smith M, Takeda A, Price A, Welch K, Somerville M. Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over. Health Technol Assess. 2008 May;12(19):iii-iv, 1-360. doi: 10.3310/hta12190.
- Teva Pharmaceutical Industries, 2010. Data on file.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Hypersensitivity, Immediate
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Asthma
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Dermatologic Agents
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Fluticasone
- Xhance
- Beclomethasone
Other Study ID Numbers
- 002/10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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