Respiratory Effectiveness Group Inaugural Collaborators’ Meeting

1. Respiratory Effectiveness Group Inaugural Collaborators’ Meeting Venue: Franklin Hall 3; Marriott Downtown, Philadelphia Date: Sunday 19 May, 2013 Time: 7.30–10.00am Contact: Alison Chisholm, REG Director: alison@effectivenessevaluation.org

2. Part 1Respiratory Effectiveness ½ Year in Review OPEN SESSION FOR REG COLLABORATORS; CURRENT AND POTENTIAL SPONSORS WELCOMED7.30 am – 8:15 am

3. Meeting Objectives • Meet each other • Review • The motivation for the group • What’s been achieved so far • What REG is funding in its first year • Share experience • What other real-life work REG collaborators are involve in? • Definition and Standards • Discuss and agree the framework for a standards document for all types of real-life research • Guidelines Group • Discuss how REGcan work with guideline groups to see real-life data better integrated within the guidelines

4. Agenda: Session 1 (open session)

5. Agenda: Session 2 (closed session)

6. The Origins of the Respiratory Effectiveness Group (REG) David Price, University of Aberdeen and REG founder7.30 am – 7:40 am

7. Evolving landscape: timeline 2008 2009 • 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 ATS/ERS Large, prospective studies in ʻreal-worldʼ settings (e.g., trials designed pragmatically to reflect everyday clinical practice) to ensure they provide content validity as well as reflect clinically meaningful outcomes 2010 ARIA / GA2LEN Proposed the use of composite measures when evaluating asthma control and called for the measurement properties to be validated in clinical trials 2011 2012 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!

8. Drivers for change: EU perspective • Clinical drivers: • On-going need to improve patient outcomes • Evidence-based decisions require representative data • Budget pressures increasing the need to demostrate: • Affordability of therapies • Value of therapies • Pharma • Bringing products to market is only the first step • Licensing ≠ approved • Licensing ≠ reimbursement • Licensing ≠ usage • Increasing need to invest in demosntrating the value proposition for new and existing products

9. Clinical drivers: representative data Efficacy x Population • Reversibility • Severity • Age / sex mix • Attitude to disease • Smoke exposure • Concomitant disease • Individual variation in response “real-life” population of patients Effectiveness

10. Clinical drivers: representative data Criteria for selecting asthma patients to a clinical trial: • Lung function 50–80% predicted • Bronchodilator reversibility • No co-morbidities • Non smokers or ex-smokers <10 pack years • Good treatment compliance • Symptomatic and regular relief medication use • Good inhaler technique Travers et al. Thorax 2007

11. Norwegian study of asthma patients to identify who would be eligible for standard clinical trials 1.2% Patient population Herland K, et al. Respir Med. 2005;99:11-9

12. Clinical drivers: representative data Does it matter if we exclude patients with: • Lesser reversibility than 20% • Active rhinitis • Smokers • Lower adherence • Poor inhaler technique AND • Design the study not like real-life? • Study only lasts 3 months? Yes!

13. Real-life research: Is it new? • Existing fields and terminology linked to real-life research: • Comparative effectiveness research (CER) • Epidemiology (pharmacoepidemiology) • Health economics (pharmacoeconomics) • Health policy (drug policy) • Pragmatic randomized controlled trials • Personalized medicine • Outcomes research (patient-centered outcomes research) • Treatment “value proposition”

14. Clinical drivers: representative data Real-life studies

15. Evidence base: hierarchy—continuum Contemporary View Traditional View Evidence continuum – complementary study designs RCTs Pragmatic Observational trials studies Experiment, observation, mathematics, individually and collectively, have a crucial role in providing the evidential basis for modern therapeutics. Arguments about the importance of each are an unnecessary distraction. Hierarchies of evidence should be replaced by accepting – indeed embracing – a diversity of approaches. Sir Michael Rawlins, Head of NICE, Lancet 2008

16. Commercial drivers… • Testing What We Think We Know. New York Times - August 19, 2012 “The truth is that for a large part of medical practice, we don’t know what works. But we pay for it anyway.” H. Gilbert Welch, MD,Geisel School of Medicine at Dartmouth

17. Development of guidelines Observational studies (pharmaco- epidemiology): Safety Cost-effectiveness Effectiveness Interventional studies (RCT): Efficacy Safety Effectiveness