Real-world Effectiveness and Cost-effectiveness of Leading Inhaled Corticosteroids in Asthma Management

Overview

The objective of the study was to compare the effectiveness, cost-effectiveness and direct healthcare costs of managing asthma in patients with evidence of persistent asthma, following the initiation and increased dose of inhaled corticosteroid (ICS) therapy using HFA-BDP (Qvar®) (either as initial therapy or as a step-up therapy) compared with the most commonly prescribed alternative ICS in the UK, CFC-beclometasone (BDP) and fluticasone (FP) as metered dose inhalers (MDIs). Qvar vs FP analyses were split between adults (12-60yrs) and paediatrics (5-11yrs).

Full Title of Study: “A Retrospective Evaluation of the Effectiveness and Cost-effectiveness of HFA-BDP MDI (Qvar®) Compared With CFC-BDP MDI and FP MDI Used in the Management of Asthma in a Representative UK UK Primary Care Population”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Retrospective
  • Study Primary Completion Date: June 2007

Detailed Description

While current UK asthma guidelines are underpinned with evidence from RCTs, much of this evidence has been undertaken in patients who are not representative of the majority of the current UK asthma population. In fact it has been estimated that fewer than 10% of the patients seen in everyday clinical practice would be eligible for inclusion in such trials. 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 and observational studies to inform existing guidelines and help optimise asthma outcomes. A more holistic approach to respiratory research would see RCT evidence complimented by "real-life" data from pragmatic trials and observational studies. A number of trends are emerged in asthma prescribing that warrant further investigation to ascertain their benefit to both the patient and the NHS. In particular, significant pressure exists to use the cheapest inhaler devices and formulations. An analysis of a pragmatic trial of Qvar versus standard CFC-BDP undertaken by Research in Real Life suggested that Qvar may be offer greater effectiveness in.5,6 In light of these data, the following report details the findings of a study designed to examine the effectiveness of Qvar in real-life clinical practice using the General Practice Research Database (GPRD).

Interventions

  • Drug: Extra-fine hydrofluoroalkane-beclomethasone dipropionate
    • Initiation of HFA-BDP (any dose) in steroid naive patients via MDI
  • Drug: Extra-fine hydrofluoroalkane-beclomethasone dipropionate
    • An increase in the baseline BDP-equivalent dose of inhaled corticosteroid as HFA-BDP via MDI
  • Drug: Fluticasone propionate
    • An increase in the baseline BDP-equivalent dose of inhaled corticosteroid as FP via MDI
  • Drug: Beclomethasone dipropionate
    • An increase in the baseline BDP-equivalent dose of inhaled corticosteroid as CFC-BDP via MDI
  • Drug: fluticasone propionate
    • Initiation of FP (any dose) via MDI in steroid naive patient
  • Drug: Chlorofluorocarbon beclomethasone dipropionate
    • Initiation of CFC-BDP (any dose) via MDI in steroid naive patient

Arms, Groups and Cohorts

  • IPDI HFA-BDP MDI
    • Patients who commenced inhaled corticosteroid therapy as HFA-BDP via MDI
  • IPDI FP MDI
    • Patients who commenced inhaled corticosteroid therapy as FP via MDI
  • IPDA FP MDI
    • Patients who had a step up in inhaled corticosteroid therapy as FP via MDI
  • IPDA HFA-BDP MDI
    • Patients who had a step up in inhaled corticosteroid therapy as HFA-BDP via MDI
  • IPDI CFC-BDP MDI
    • Patients who commenced inhaled corticosteroid therapy as CFC-BDP via MDI
  • IPDA CFC-BDP MDI
    • Patients who had a step up in inhaled corticosteroid therapy as CFC-BDP via MDI

Clinical Trial Outcome Measures

Primary Measures

  • Proxy asthma control
    • Time Frame: One-year outcome period
    • Primary composite measure asthma control defined as: No recorded hospital attendance for asthma including admission, Accident & Emergency (A&E) attendance, out of hours attendance or Out-Patient Department (OPD) attendance, AND No prescriptions for oral steroid, AND No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics.

Secondary Measures

  • Revised asthma control
    • Time Frame: One-year outcome period
    • A revised definition of proxy asthma control for sensitivity analysis was defined as: No recorded hospital attendance for asthma including admission, A&E attendance, out of hours attendance or OPD attendance, AND No prescriptions for oral steroid, AND No consultations, hospital admissions or A&E attendance for lower respiratory tract infections (LRTI) requiring antibiotics Average daily prescribed dose of salbutamol of no more than 200mcg and terbutaline 500mcg.
  • Disaggregated components of the primary control outcome
    • Time Frame: One-year outcome period
    • Hospital admissions for asthma Consultations and hospital attendances for LRTI requiring antibiotics Prescriptions for oral steroids SABA use
  • Time to the first asthma exacerbation
    • Time Frame: One-year outcome period
    • Where an exacerbation is defined as: An occurrence of unscheduled hospital admission/A&E attendances for asthma AND/OR Use of oral steroids.
  • Success of the therapeutic regimen
    • Time Frame: One-year outcome period
    • Defined as: Exacerbation AND/OR Increase in dose of ICS AND/OR Change in ICS drug type AND/OR Change in delivery device AND/OR Use of additional therapy as defined by: LABAs, oral steroids, theophylline, leukotriene receptor antagonists (LTRAs)
  • Use of anti-fungals
    • Time Frame: One-year
    • defined as incidences of definite oral candidiasis
  • Daily dose of ICS (BDP equivalent) at week 52 compared with week 0 and proportion on original dose of BDP Daily dose* of ICS (BDP equivalent) at week 52 compared with week 0 and proportion on original dose of BDP.
    • Time Frame: One-year outcome period
    • BDP-equivalent dose were calculated by multiplying the Qvar and FP doses by a factor of 2. The dose at week 52 was compared with that at week 0 in order to identify the proportion of original (week 0) ICS dose.

Participating in This Clinical Trial

Inclusion Criteria

Included patients must:

  • aged 5-60 years – evidence of asthma: a diagnostic code of asthma or ≥2 prescriptions for asthma in baseline year at different points in time including one of ICS – on current therapy at the IPD, defined as ≥1 ICS script and ≥1 other asthma prescriptions in the 12 months prior to first change in therapy – had 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. Exclusion Criteria:

  • 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 – For the therapy increase patient cohort, any patients receiving a combination inhaler in addition to their separate ICS inhaler in the year prior to IPD were also excluded.

Gender Eligibility: All

Minimum Age: 5 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Research in Real-Life Ltd
  • Collaborator
    • Teva Branded Pharmaceutical Products R&D, Inc.
  • Provider of Information About this Clinical Study
    • Professor David Price, Research in Real Life Limited
  • Overall Official(s)
    • David Price, Prof. MD, Principal Investigator, Company Director
    • Alison Chisholm, MSc, Study Director, Research Project Director

References

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.

Thomas M, Cleland J, Price D. Database studies in asthma pharmacoeconomics: uses, limitations and quality markers. Expert Opin Pharmacother. 2003 Mar;4(3):351-8. doi: 10.1517/14656566.4.3.351.

Tannen RL, Weiner MG, Xie D. Use of primary care electronic medical record database in drug efficacy research on cardiovascular outcomes: comparison of database and randomised controlled trial findings. BMJ. 2009 Jan 27;338:b81. doi: 10.1136/bmj.b81.

Juniper EF, Price DB, Stampone PA, Creemers JP, Mol SJ, Fireman P. Clinically important improvements in asthma-specific quality of life, but no difference in conventional clinical indexes in patients changed from conventional beclomethasone dipropionate to approximately half the dose of extrafine beclomethasone dipropionate. Chest. 2002 Jun;121(6):1824-32. doi: 10.1378/chest.121.6.1824.

Price D, Haughney J, Duerden M, Nicholls C, Moseley C. The cost effectiveness of chlorofluorocarbon-free beclomethasone dipropionate in the treatment of chronic asthma: a cost model based on a 1-year pragmatic, randomised clinical study. Pharmacoeconomics. 2002;20(10):653-64. doi: 10.2165/00019053-200220100-00002. Erratum In: Pharmacoeconomics 2002;20(12):853.

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. doi: 10.1016/0021-9681(87)90171-8.

Cliniclue [homepage on the internet]. The Clinical Information Consultancy CLINICLUE® [updated 2008; cited 15 May 2009]. Available online at: http://www.cliniclue.com

SPSS [homepage on the internet]. Chicago: SPSS Inc [updated 2009; cited 15 May 2009]. Available online at: http://www.spss.com/UK/

Microsoft office online [homepage on the internet]. USA: Microsoft Corporation [updated 2009; cited 15 May 2009]. Available online at: http://office.microsoft.com/excel

STATA: Data Analysis and Statistical Software [homepage on the internet]. Texas: STATA [updated 2009; cited 15 May 2009]. Available online at: http://www.stata.com/

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.