Clinical trial NCT01287351: Real-world Effectiveness and Cost-effectiveness of Qvar Versus FP, a US Study
Official title: 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 type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Keywords: Real-world
observational
Fluticasone propionate
Metred dose inhaler
Extra-fine hydrofluoroalkane
Asthma management
Inhaled corticosteroids
Beclomethasone dipropionate
USA
Lead sponsor: Research in Real-Life Ltd
Sponsor class: NETWORK
Collaborators: name: i3 Research
name: Teva Branded Pharmaceutical Products R&D, Inc.
First posted: 2011-02-01
Enrollment: 82903
Sex: ALL
Minimum age (years): 5
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proxy Asthma Control
timeFrame: One-year outcome period
measure: Total number of asthma exacerbations and exacerbation rate ratio
timeFrame: One-year outcome period
measure: Revised proxy asthma control
timeFrame: One-year outcome period
measure: Risk Domain Asthma Control (in the subgroup of patients aged 12-60, the following additional analysis was done)
timeFrame: One year outcome period
Secondary outcomes:
measure: Asthma control plus no additional or change in therapy
timeFrame: One-year outcome period
measure: Asthma control plus no additional change in therapy (where change is not driven by possible cost saving)
timeFrame: One-year outcome period
measure: Respiratory-related hospitalizations and referrals
timeFrame: One-year outcome period
measure: Overall asthma control (Risk and Impairment) (in the subgroup of patients aged 12-60, the following additional analysis was done)
timeFrame: One year outcome period
measure: Health Economic analysis
timeFrame: One year outcome period
measure: Cost-effectiveness analysis
timeFrame: One year outcome period
Other outcomes:
Locations:
city: Cawston
country: United Kingdom
facility: Research in Real Life
state: Norfolk
Study officials:
References:
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citation: Teva Pharmaceutical Industries, 2010. Data on file.