Obstructive Sleep Apnoea Working Group Meeting

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Text of Obstructive Sleep Apnoea Working Group Meeting


    Dr Mihaela Stefan

    DATE: Saturday September 3rd

    TIME: 5.006.15pm

    VENUE: Royal College of General Practitioners; 30 Euston Square, London, UK

  • Agenda

    17.00-17.15 Welcome / Introduction

    OSA new area for REG research...?

    17.15-17.45 A first research idea

    Clinical and Cost Implications of PAP in patients with OSA

    and Obstructive Lung Disease

    17.45-18.10 Other potential projects for the group

    18.10-18.15 Next Steps & Meeting Close

  • The Respiratory Effectiveness Group (REG)

    Founded in October 2012 by David Price, Professor of Primary Care Respiratory Medicine at the University of Aberdeen.

    Recognised the growing importance of real-life research and the need for respiratory experts around the world to come together to:o De-fragment practice o Set best practice quality standardso Set a unified agenda for future ethical and meaningful real-life research.

  • Evolving landscape: timeline

    Brussels Declaration on Asthma: stated a need to include evidence from real world studies in treatment guidelines

    Michael Rawlins (NICE Chairman): RCTs should be complemented by a diversity of approaches that involve analysing the totality of the evidence base



    Large, prospective studies in real-world settings (e.g., trials designed pragmatically to reflect everyday clinical practice) to ensure they provide content validity as well as reflect clinically meaningful outcomes



    Proposed the use of composite measures when evaluating asthma control and called for the measurement properties to be validated in clinical trials


    NHLBI expert workshop Highlighted areas that need strengthening in order to optimize the potential of real-life/comparative effectiveness (CER) research in pulmonary diseases, sleep, and critical care.


    REG was founded!


  • Studies have shown that efficacy RCTs exclude about 95% of asthma and 90% of COPD routine care populations due to strict inclusion criteria.1

    1. Herland K, et al. Respir Med 2005;99:1119.

    Limitations: RCTs inclusions/exclusions



    Patient RCT eligibility drop-off with sequential application of standard inclusion criteria

  • Evidence


    Theoretical model provide


    Classical double-blind double-dummy RCTs

    Gold standard, large range of

    outcomes. But not real-life patients,

    compliance and represent

  • Working groups: specialty focus

    Not-for profit, international research and advocacy group

    Investigator-led; 5 executive members providing leadership

    >300 collaborators spanning 40 countries

    14 Working groups to identify research needs in areas where real-world research methodologies have particular utility




  • Background: OLDOSA OLD-OSA overlap syndrome refers to the coexistence of OLD

    (obstructive lung disease: COPD and asthma) and OSA

    A broader umbrella term of OLDOSA syndrome is proposed1

    1. Ioachimescu OC, et al. Respirology. 2013;18:421-31; 2

  • Background: OLDOSA WHY? Obesity is a growing problem worldwide1

    Obesity predisposes OSA.2 Possible link between obesity and OLD:

    o Positive correlation between baseline BMI and the subsequent development of asthma3

    o Rhinitis4,5 and GERD68 are common risk factors to both asthma and OSA

    OSA is an independent risk factor for asthma exacerbations8 Prevalence of comorbid OSA may be increasing with increasing asthma


    No population-based studies using polysomnography to identify the prevalence and severity of OSA in routine care asthma patients

    Patients with COPD and OSA have higher mortality than those with COPD and Tx with CPAP reduces COPD exacerbations11

    1.WHO: http://www.who.int/mediacentre/factsheets/fs311/en/ . 2.Romero-Corral A, et al. Chest. 2010;137:711719; 3. Delgado J, et al. J Inv Aller Clin Immunol. 2008;18:420-5; 4. Staevska MT, et al. Curr Allergy Asthma Rep,2004;4:193; 5. Ing AJ, et al. Am J Med. 2000;1 08(Suppl 4a):120S5S; 6. Avidan B, et al. Gut. 2001;49:76772; 7. Cibella F, et al. Am J Med. 2001;111(Suppl 8A):31S6S; 8. Ten Brinke A, et al. Eur Respir J. 2005;26:8128; 9. Julien JY, et al. JACI. 2009;124:371-6; 10. Alkhalil M, et al. Clin Sleep Med. 2009; 5: 7178 11.Marin JM et al. AmJ Respir. Crit, Care. Med. 2010;182:325-31

  • Background: PAP

    Positive airway pressure (PAP) is the most effective treatment for patients with moderate-to-severe obstructive OSA.1

    Real-life evidence (claims data) suggests PAP is an effective and cost-effective OSA treatment. Compared with baseline:2 o PAP associated with 41% lower healthcare and disability costs and

    fewer missed

    o Healthcare costs in controls (diagnosed with OSA but untreated) decreased by 8%

    o Healthcare costs increased by 34% in those without OSA over the same period

    Small observational studies suggests that PAP Tx may attenuated the risk of severe asthma in patients with comorbid OSA, particularly in older patient groups.3

    1. Hoffman B, et al. J Occup Environ Med.2010;52:473-7; 2. Teodorescu M, et al. Sleep Disord. 2013; 2013: 251567;

    3. Albarrak M et al. Sleep. 2005;28:1306-11.

  • Possible Beneficial Effects of PAP in Patients with Asthma and OSA

  • Need to understand the inter-relationship between OSA-Asthma-COPD and the real-life implications of undiagnosed or inadequately treated OSA on OLD, and vice versa.

  • Aim

    To evaluate the impact of a diagnosis of sleep-related breathing disorder (SBD, including OSA) on clinical outcomes and healthcare resource utilization in a representative population of patients with OLD and comorbid SBD in the United Kingdom.

    Hypothesis: It is assumed that a diagnosis of OSA

    (surrogate marker for treatment) will be associated with a decrease in the use of health care resources.

  • Design & Data source

    Design Historical matched cohort study using electronic medical records

    and linked questionnaire data from the Optimum Patient Care Research Database (OPCRD)

    Data source The Optimum Patient Care Research

    Database (OPCRD) is a UK primary care database available to REG: o Quality-controlled, longitudinal, primary-care database o Contains anonymous data from 550 UK general practices

    & ~2.5 million patients

    o Captured via the OPC asthma and COPD clinical review service Respiratory enriched database

    o Ethical approval for medical research

  • Study Population Inclusion criteria Active Population Control Population

    Aged: 18 years at index date

    A physician diagnosis of SDB (defined as 1 SBD diagnostic codes)


    3 years of continuous data: 1 year prior to index date 2 years immediately after index date

    OLD Diagnosis, any of: Asthma subpopulation: asthma diagnosis ever prior to index date, 2 asthma prescriptions in the baseline year; no COPD Read code in the 3-year study period COPD subpopulation: COPD diagnosis ever prior to index date, 2 COPD prescriptions in each of the baseline years; no asthma Read code in the 3-year study period Asthma & COPD subpopulation: Asthma & COPD diagnoses within 2 years of each other ever prior to the index date and 2 OLD prescriptions in each of the baseline years; no asthma or COPD resolved codes within the study period

    Exclusion criteria Active Population Control Population

    To optimise the external validity of the study findings no exclusion criteria will be applied

  • Study Period

    The study will consider a three-year continuous observation period for eligible patients

    1 baseline year immediately before the index date (months -120)

    Index date (date/month 0) will be: o Active cohort: the data of first SDB diagnosis o Control cohort: date of a random primary care consultation in

    matched controls

    2 outcome years immediately following the index date o Primary analysis: 24-month outcome period, months 0-24 (for

    evaluation of all primary and secondary endpoints) o Secondary analysis: 21-month outcome period, months 0-24 (for

    primary endpoint evaluation only)

  • Study Design

    Index Date:

    Active: Date of first OSA diagnosis Control Group: healthcare consultation date in patients matched on age,

    BMI, sex and OLD diagnosis, OLD severity

    Baseline: 1 year Outcome: 2 years

    (primary: months 0-24)

    Active Arm

    Control Arm


    Primary: Acute respiratory event rate Secondary: Acute care hospital days (total days/period) Pharmaceutical dispensations (days supply/period) Overall healthcare costs

    Outcome: 21 month (secondary: months 3-24)

    Month 0

    Month 3

  • Primary endpoint

    Acute respiratory event rate Defined as the occurrence of any of the following events

    coded for a lower respiratory complaint: o Hospital admission o Emergency Room / Accident & Emergency attendance o Acute course of oral steroid prescription o Antibiotics prescriptions.

  • Endpoints: secondary

    Healthcare resource utilization Primary care consultations:

    o All o For SDB o For a lower respiratory complaint o For