Ideas so far…

1. Ideas so far… REG member comments and suggestions

2. General comments • “…the time is ripe for some sort of initiative in the area. Careful thought will be needed as to the best way to tap into this.”Mike Thomas • “We should aim to produce research which is applicable to guidelines and which can ensure their longevity & relevance.” Daryl Freeman • Most value will be in creating opportunities for face-to-face opportunities to forge common purpose and expose potential synergies in research interests and methods, and for discussing joint projects…” Eric Bateman

3. Defining meaningful outcome measures Global measure for systemic therapies: • Development a clinical outcome measure that captures both asthma-related symptoms and comorbidities( such as atopic dermatitis, rhinitis, conjunctivitis and sinusitis). Systemically-acting drugs, such as LTRAs and biologics, influence each of these but have an overall effect on health and well-being greater than the sum of the individual organ-related parts, we need a global assessment measure. Stephen Holgate Patient-defined outcomes not guideline-defined outcomes, e.g.: • What level of real-life compliance is optimum? • Higher compliance is not always associated with better disease management (i.e. more severe patients with greater dependence on therapy) • Discrete choice experiment (DCE)? Christian Virchow “Develop novel real-life parameters to evaluate symptoms / quality of life”Claus Vogelmeier

4. Real-life inhaler selection • What drives successful use of different inhaler types? Federico Lavorini • Mis-assigning inhalers can be costly • Optimise device to patient • Challenges: • Device selection is often governed by national heritage • Physician familiarity with a device and appropriate training can affect education and outcomes. • Pharma funding discredits results… possibility of government funding? • Opportunities: • Study comparing turbohaler vs diskus vs spiromax study – opportunity for DPI crossover after the sponsored study? • Mundipharma step-down study (from Diskus to MDI or to Diskus) may provide a signal?

5. PUBLICATION, COMMUNICATION,DISSEMINATION

6. Communications • Congresses • Which ones? • Abstracts • Session ideas? • REG prize? • Publications • Reviews • Editorials • Manifesto • Letter of intent

7. Manifesto and letters of intent Manifesto • The group should develop a manifesto for change, covering the • Need for improved standards in real-life research • Need for greater recognition and integration of real-life search in the current evidence base • Challenges faced by real-life research • Published in the ERJ or the Lancet Respiratory Alberto Papi Letter • Publish a letter on behalf of the group (signed by all core steering committee members) endorsing the value of the initiative. Circulate it to potential sponsors. Andrew McIvor

8. Conferences: ERS 2013 • Abstracts: • Endpoints for observational asthma studies – the current state of the art • The real relationship between adherence and outcomes – a need for more patient-focussed outcome measures • Deadline February 21st

9. Conferences: ERS 2014 and beyond • Resubmit the existing proposal? (submission begins in March 2013) • Need to lobby for a session in Munich: • Talk with different assembly heads to see who can best promote the ideas internally to the right assembly or assemblies • REG members could attend each of the respective assembly meetings in Barcelona to talk about the importance of the issue. • Approach assemblies to suggest poster / poster discussion / oral communication session(s) dedicated to real-life effectiveness studies • Could propose a joint symposium with: • The European Lung Foundation (ELF) – look at real-life research from the patients’ perspective:  “Reflecting the needs of all patients in the real-world” • Some REG members are involved in the GINA and GOLD committees – a proposal for a common GINA + GOLD + REG session: “How effectiveness studies could be taken into accounted by guideline developers based on some specific examples of evidence.”

10. Conferences: ERS 2014 and beyond • Hot topic suggestions • Association between the different biomarkers used in clinical assessment of asthma (screening and follow-up). • Data from non-selective populations – real-life clinical settings. • What to be used, and what not e.g: smoking patients, • In case of infrequent dose of inhaled steroid, respiratory infection within 4 or 6 weeks – what to do ?  • A surrogate variable for sputum counting, e.g. sputum supernatant for IL8 (neutrophilia) or other…?   • Sport: • Asthma evaluation • Doping and sport

11. Alternative conferences Propose sessions to multiple congresses: • EAACI • “excellent alternative – large meeting with many knowledge-rich delegates” • “EAACI could be an excellent future collaborative partner” • IPCRG – Athens 2014: • Plenary – UNLOCK (asthma history / future in COPD); Using real-life data to answer questions – inhaler type; initiation and step-up options; patient sub-groups (smokers, atopic patients); DOSE index and validation. • Miguel to propose at scientific committee • Other options include: AAAAI / ATS / ISPOR / BSACI…?

12. Congresses: strategic approach • Need to raise awareness/importance of the topic before acceptance from societies, by: • Continued abstract submissions to various societies.   • Will slowly gain awareness. • Continued submissions for a program slot.   • A long shot initially. • Various journals have supplement journals (such as the Annals of the ATS) that accept a theme topic for the entire supplement.   • Usually has a significant price tag, but REG funding might afford it and could jump start the awareness and importance aspect of real life trials.   • Downstream affect would be a society(ies) slot.

13. Congress: hold our own meeting? • Hold a planning meeting at the ERS in Barcelona: • Get the group together and plan a strategy and collaborative research projects? • Brainstorm about holding an REG-organised 1–2 day meeting on this real-life research?

14. SETTING STANDARDS

15. Setting standards • Suggestions so far: • Validation work – discussed • Registry? • Code sharing • Standardising terminology, lexicon and study design to allow comparisons • Where do pragmatic trials fit? • How to define an implementation study

16. A real-life study registry • Provide a registration service for real-life studies pragmatic clinical trials and observational studies. • Current registries are designed for RCTs – square peg; round hole? • Benefits: • Mandate entry of meaningful, minimum data entry • Create a central repository or real-life research • Serve as a quality marker of high-quality research • Provide “peer review” of protocols at the point of submission • Stop US monopoly on study registration  • The respiratory journal editors are going to mandate that all studies MUST be registered (observational, pragmatic trials, RCTs) • Develop the registry in collaboration with the respiratory journal editors? • The journals editors could promote the registry on behalf of the group

17. Code sharing • Share code lists among the research community • Enable peer review of research codes and standardisation of coding methods • Share different lists of codes for different coding systems: • Read codes (UK) • ICD codes • Host code lists on the REG website • Password protected area for members only • Consider how to combine data sets for maximum power and to gain collaborative experience.  • E.g. Pooled OPCRD and CPRD data for the pediatric asthma study (previously discussed)

18. Defining standards and lexicon Protocol review service: • Another task of the group could be to support others when they want to develop a real-life research project, the group acting as a consultant for methodology. Nicolas Roche Re-defining the lexicon • Efficacy and effectiveness are too interlinked… they’re often confused. • Use instead: • Does the drug work? (efficacy) • Does the drug help? (effectiveness) • Even placebo can help in the real-world. Christian Virchow  

19. Pragmatic trials & implementation studies (I) • Are pragmatic trials within the scope of REG – yes…? • The issues / benefits / limitations associated with different types of real-life research (observational research / pragmatic trials) differ and should be clearly set out. Mike Thomas • Eric Bateman and colleagues have conducted several pragmatic randomised controlled trials in large primary care populations – they would be pleased to interact with those interested in large-scale healthcare interventions focusing on respiratory diseases. Eric Bateman

20. Pragmatic trials & implementation studies (III) REG should: • Consider publishing a methodology paper on the challenges faced in real-life research • Define implementation studies. A recent review of the literature for self-management of long-term conditions found it difficult to: • Set up searches which identify implementation studies • Screen the abstracts due to lack of standard terminology • Evaluate whether a study was truly possible to implement (due to poor description of the methodology and inconsistent terminology) – editors tend to view implementation studies as (cluster) RCTs (and apply the checklist) which does not necessarily work Hilary Pinnock

21. Pragmatic trials & implementation studies (II) • It is important to design and undertake: • Pragmatic clinical trials • Population-level implementation studies (e.g. stepped wedge or interrupted time series) of sufficient quality and designed that they can be assessed by guideline bodies and inform guidance. Hilary Pinnock

22. COLLABORATIONS

23. Collaborations • Interactions with others… • Guideline bodies • Societies • GOLD, GINA • EACCI, AAAAI • ISPOR, IPCRG • ERS, ATS… • Regulatory authorities • Government departments • Patient groups • PR and media?

24. Guidelines: comments • “Guidelines currently act as a repository of knowledge, but lack clinical meaning and can be inaccessible • To resume their utility as a pillar of evidence-based medicine, current guideline methodology requires systematic challenge • Research needs to be able to assist in the systemic challenge of existing guidelines” Dermot Ryan • “There is a long way to go from ‘efficacy for an intervention based upon RCTs’ towards ‘recommendation for an intervention in daily practice’. In addition to efficacy data, physicians and patients need data on: • Real-life effectiveness • Long-term safety • Cost-effectivenessGuy Brusselle

25. Guidelines: suggested actions (I) WHAT? • REG should accelerate the acceptance of real-life research by guideline writers? Kevin Gruffydd-Jones, Alberto Papi HOW? • Evidence grading standards: Propose quality criteria for different types of real-life research. Standards will assist in deciding whether a study should be taken into account by guidelines bodiesNicolas Roche • Grading scale: Develop a quantitative scale for grading evidence along the efficacy to effectiveness continuum (based on the Kevin Thorpe framework).  Jerry Krishnan

26. Guidelines: suggested actions (II) • Its time to move away from guideline-defined outcomes and towards patient-defined outcomes. Patient-perception is of importance. • Guideline-defined lack of control, may not be perceived as poor control to a patient. • ≥100% adherence ≠ well controlled asthma • Is risk more important than control? Christian Virchow • Add short supplementary paragraphs to GINA recommendations: • “What would this guideline look like if it were to incorporate real-life data” • Published in the Lancet – Respiratory (e.g. ATS or ERS special edition) Alberto Papi