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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Fluticasone propionate metred dose inhaler; Drug: Fluticasone propionate metred dose inhaler; Drug: Extra-fine hydrofluoroalkane beclomethasone MDI; Drug: Chlorofluorocarbon beclomethasone metered dose inhaler; Drug: Chlorofluorocarbon beclomethasone dipropionate; Drug: Hydrofluoroalkane beclomethasone metred dose inhaler

Detailed Description

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:

1. before a diagnosis of COPD is made
2. 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.

• Study Type: Observational
• Enrollment (Actual): 815377

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW8 5NQ
    • General Practice Research Database

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Primary care COPD patients who at an index prescription date either initiated ICS therapy as extrafine HFA-BDP, CFC-BDP or FP via MDI or had an increase in baseline BDP-equivalent ICS dose the index data as extrafine HFA-BDP, CFC-BDP or FP via MDI

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IPDA FP MDI; 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; Step-up in baseline BDP-equivalent ICS dose; Drug: Fluticasone propionate metred dose inhaler; Initiation of ICS therapy
IPDA HFA-BDP MDI; 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; Step-up in baseline BDP-equivalent ICS dose; Other Names: Qvar®
IPDA CFC-BDP MDI; 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; Step-up in baseline BDP-equivalent ICS dose
IPDI CFC-BDP MDI; 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; Initiation of ICS therapy
IPDI HFA-BDP MDI; 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; Initiation of ICS therapy; Other Names: Qvar®
IPDI FP MDI; 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; Step-up in baseline BDP-equivalent ICS dose; Drug: Fluticasone propionate metred dose inhaler; Initiation of ICS therapy

What is the study measuring?

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) andLower 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:AdmissionA&E attendanceOut 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:LABATheophyllineLTRAs.	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:LABATheophyllineLTRAs.	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, orfor COPD; Admissions and A&E coded as:lower respiratory-related, orfor COPDadmission 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, orhospitalisation 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

Collaborators and Investigators

• Sponsor: Research in Real-Life Ltd
• Collaborators: Teva Branded Pharmaceutical Products R&D, Inc.

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.
• Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J. 1998 Dec;12(6):1346-53. doi: 10.1183/09031936.98.12061346.
• Barber JA, Thompson SG. Analysis and interpretation of cost data in randomised controlled trials: review of published studies. BMJ. 1998 Oct 31;317(7167):1195-200. doi: 10.1136/bmj.317.7167.1195.

Helpful Links

• Optimum Patient Care is the Research in Real Life's sister company (a social enterprise organisation)

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): June 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 9, 2010
• First Posted (Estimate): June 10, 2010

Study Record Updates

• Last Update Posted (Estimate): March 8, 2011
• Last Update Submitted That Met QC Criteria: March 7, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: exacerbations; chronic obstructive pulmonary disease; inhaled corticosteroid; increase; initiate; treatment success
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; 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: BA5