Skip to main content

Main menu

  • Home
  • Current issue
  • Early View
  • Archive
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • Early View
  • Archive
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • COVID-19 submission information
    • Institutional open access agreements
    • Peer reviewer login
  • Alerts
  • Subscriptions

Clinical effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol in usual practice: the COPD INTREPID study design

Sally Worsley, Neil Snowise, David M.G. Halpin, Dawn Midwinter, Afisi S. Ismaila, Elaine Irving, Leah Sansbury, Maggie Tabberer, David Leather, Chris Compton
ERJ Open Research 2019 5: 00061-2019; DOI: 10.1183/23120541.00061-2019
Sally Worsley
1Medical Engagement & Value Evidence and Outcomes, GlaxoSmithKline plc., Stevenage, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: sally.d.worsley@gsk.com
Neil Snowise
2Global Respiratory Franchise, GlaxoSmithKline plc., Brentford, UK
3Faculty of Life Sciences and Medicine, King's College, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David M.G. Halpin
4Dept of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dawn Midwinter
5Clinical Statistics, GlaxoSmithKline plc., Stockley Park, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Afisi S. Ismaila
6Medical Engagement & Value Evidence and Outcomes, GlaxoSmithKline plc., Collegeville, PA, USA
7Dept of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elaine Irving
1Medical Engagement & Value Evidence and Outcomes, GlaxoSmithKline plc., Stevenage, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leah Sansbury
6Medical Engagement & Value Evidence and Outcomes, GlaxoSmithKline plc., Collegeville, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maggie Tabberer
8Medical Engagement & Value Evidence and Outcomes, GlaxoSmithKline plc., Stockley Park, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Leather
2Global Respiratory Franchise, GlaxoSmithKline plc., Brentford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chris Compton
2Global Respiratory Franchise, GlaxoSmithKline plc., Brentford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Figures

  • Tables
  • FIGURE 1
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 1

    INTREPID study design. Only two study visits (baseline and week 24) will be required during the INTREPID study. FEV1 and critical error assessments will be conducted in select patient subgroups only. CAT: COPD assessment test; COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 s; ICS: inhaled corticosteroid; LABA: long-acting β2-agonist; LAMA: long-acting muscarinic antagonist; R: randomisation. #: ICS/LAMA/LABA multiple-inhaler triple therapy, LAMA/LABA combination dual therapy or ICS/LABA combination dual therapy.

  • FIGURE 2
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 2

    Recruitment models employed across countries. CRO: contract research organisation; DE: Germany; NL: the Netherlands; PI: principal investigator; PIC: patient identification centre; SP: Spain; SWE: Sweden; UK: United Kingdom.

Tables

  • Figures
  • TABLE 1

    A comparison of the key features that differ between conventional randomised controlled trials (RCTs) and effectiveness trials

    Conventional RCTsRandomised effectiveness trials
    Trial settingOften academic/research centres specially equipped for clinical research, which patients may have to travel considerable distance to attend [5].
    Trial patients often attend frequent, regular study visits with a specialist investigator [5].
    Patients are provided with regular training during study visits to ensure optimal medication use and adherence [6]. Adherence to study medication is monitored.
    Routine care practices and hospitals.
    Patients treated by their (local) regular healthcare provider in accordance with usual clinical care; limited or no study-specific visits required.
    Training and medication guidance is given as part of usual clinical care. This varies between sites and countries.
    Patients may change their treatment at physician or patient discretion.
    Patient selectionNarrow population due to strict inclusion and exclusion criteria [7, 8]; recruitment of patients with comorbid conditions and concomitant medications is limited [5, 7–9].Enrolment of a broader patient population creates high external validity as patients are more representative of the population seen in usual practice [8, 10].
    Key differences between protocol-defined study treatments and those given in clinical practiceOften employ a placebo group or strictly controlled comparator group to enable direct comparison of pure drug effects providing high internal validity [10].Comparator treatments are aligned with physician and country usual standard of care.
    Measurement of outcomesOutcomes often those required by regulatory authority, which may not be used in the routine care of patients, such as physiological end-points or biomarkers [11].Selected end-points are relevant to usual practice and include a more patient-centred focus [8].
    Safety monitoringExclusion of “high-risk” patients most likely to experience safety issues [5, 9].
    Safety is closely monitored by investigators at each study visit.
    Enrolment of a wider population of patients allows collection of more generalisable safety data [10].
    Patient safety is ensured through treating physicians during routine study visits or planned telephone calls.
  • TABLE 2

    Key inclusion and exclusion criteria of the INTREPID study

    Inclusion criteria
     Informed consent: capable of giving signed, informed consent
     Age and sex: male and female aged ≥40 years
     COPD diagnosis: documented physician diagnosis of COPD
     Severity of COPD symptoms: a score of ≥10 on CAT at screening
     History of exacerbations: a history of treatment with systemic/oral corticosteroids, antibiotics and/or hospitalisation for ≥1 COPD exacerbation in the 3 years prior to randomisation#
     Existing COPD maintenance treatment: currently receiving one of the below non-ELLIPTA maintenance therapies and have been prescribed it continually for ≥16 weeks prior to randomisation:
      ICS in combination with LAMA and LABA (MITT)
      LAMA and LABA combination therapy¶
      ICS and LABA combination therapy¶
    Exclusion criteria
     Unstable COPD: resolution of an exacerbation within 2 weeks of visit 1+
     Prior/concomitant therapy with oral corticosteroid: chronic use of oral corticosteroid for respiratory or other indications in the opinion of the investigator§
     Women of child-bearing potential: women who are pregnant, lactating or planning to become pregnant during the study period
     Medical conditions: any illness judged in the opinion of the investigator to cause a low probability of 6-month survival
     Other diseases/abnormalities: historical or current evidence of uncontrolled or clinically significant diseaseƒ
     Hypersensitivity: history of hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, β2-agonist, lactose/milk protein or magnesium stearate, or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, contraindicates study participation
     Participation in interventional clinical studies: taking part in any investigational drug treatment within 30 days or five half-lives of the prior investigational drug before visit 1

    CAT: COPD assessment test; LAMA: long-acting muscarinic antagonist; LABA: long-acting β2-agonist; MITT: multiple-inhaler triple therapy; ICS: inhaled corticosteroid. #: captured through patient recall and/or medical records and must be documented in patient notes. Prior use of systemic/oral corticosteroids and/or antibiotics alone does not qualify as exacerbation history unless treatment was associated with the worsening of COPD symptoms. ¶: patients on dual maintenance therapy on enrolment must be considered by their physician to require a step-up to triple therapy and the reason for the physician decision must be documented. +: patients may be rescreened 2 weeks after resolution of an exacerbation. §: chronic use is defined as more than 14 days' continuous use during the 12 weeks prior to visit 1; ƒ: significant disease is defined as any disease that, in the opinion of the investigator, would put the safety of the patient at risk by participating, or would impact the effectiveness or safety analysis if the disease/condition exacerbated during the study.

    PreviousNext
    Back to top
    Vol 5 Issue 4 Table of Contents
    ERJ Open Research: 5 (4)
    • Table of Contents
    • Index by author
    Email

    Thank you for your interest in spreading the word on European Respiratory Society .

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Clinical effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol in usual practice: the COPD INTREPID study design
    (Your Name) has sent you a message from European Respiratory Society
    (Your Name) thought you would like to see the European Respiratory Society web site.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Print
    Citation Tools
    Clinical effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol in usual practice: the COPD INTREPID study design
    Sally Worsley, Neil Snowise, David M.G. Halpin, Dawn Midwinter, Afisi S. Ismaila, Elaine Irving, Leah Sansbury, Maggie Tabberer, David Leather, Chris Compton
    ERJ Open Research Oct 2019, 5 (4) 00061-2019; DOI: 10.1183/23120541.00061-2019

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    Share
    Clinical effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol in usual practice: the COPD INTREPID study design
    Sally Worsley, Neil Snowise, David M.G. Halpin, Dawn Midwinter, Afisi S. Ismaila, Elaine Irving, Leah Sansbury, Maggie Tabberer, David Leather, Chris Compton
    ERJ Open Research Oct 2019, 5 (4) 00061-2019; DOI: 10.1183/23120541.00061-2019
    del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
    Full Text (PDF)

    Jump To

    • Article
      • Abstract
      • Abstract
      • The importance of randomised controlled trials and factors limiting their applicability to usual clinical practice
      • An introduction to effectiveness studies
      • Rationale for the INTREPID study
      • INTREPID: protocol of a randomised effectiveness study in usual practice
      • Conclusion
      • Acknowledgements
      • Footnotes
      • References
    • Figures & Data
    • Info & Metrics
    • PDF

    Subjects

    • COPD and smoking
    • Pulmonary pharmacology and therapeutics
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    More in this TOC Section

    • Eradication of early MRSA infection in cystic fibrosis
    • AROMA
    • The disease-specific clinical trial network for PCD
    Show more Study protocols

    Related Articles

    Navigate

    • Home
    • Current issue
    • Archive

    About ERJ Open Research

    • Editorial board
    • Journal information
    • Press
    • Permissions and reprints
    • Advertising

    The European Respiratory Society

    • Society home
    • myERS
    • Privacy policy
    • Accessibility

    ERS publications

    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS books online
    • ERS Bookshop

    Help

    • Feedback

    For authors

    • Instructions for authors
    • Publication ethics and malpractice
    • Submit a manuscript

    For readers

    • Alerts
    • Subjects
    • RSS

    Subscriptions

    • Accessing the ERS publications

    Contact us

    European Respiratory Society
    442 Glossop Road
    Sheffield S10 2PX
    United Kingdom
    Tel: +44 114 2672860
    Email: journals@ersnet.org

    ISSN

    Online ISSN: 2312-0541

    Copyright © 2023 by the European Respiratory Society