Respiratory Effectiveness Group Inaugural Collaborators’ Meeting

Venue: Franklin Hall 3; Marriott Downtown, PhiladelphiaDate: Sunday 19 May, 2013Time: 7.30–10.00am

Contact: Alison Chisholm, REG Director: alison@effectivenessevaluation.org

Part 1

Respiratory Effectiveness ½ Year in Review OPEN SESSION FOR REG COLLABORATORS; CURRENT AND POTENTIAL SPONSORS WELCOMED

7.30 am – 8:15 am

Meeting Objectives• Meet each other

• Reviewo The motivation for the groupo What’s been achieved so faro What REG is funding in its first year

• Share experienceo What other real-life work REG collaborators are

involve in?

• Definition and Standards o Discuss and agree the framework for a standards

document for all types of real-life research

• Guidelines Groupo Discuss how REG can work with guideline groups to

see real-life data better integrated within the guidelines

Agenda: Session 1 (open session)

Agenda: Session 2 (closed session)

The Origins of the Respiratory Effectiveness Group (REG)David Price, University of Aberdeen and REG founder

7.30 am – 7:40 am

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

2008

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

2009

ARIA / GA2LEN

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

2010

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

2011

REG was founded!

2012

Drivers for change: EU perspective• Clinical drivers:

o On-going need to improve patient outcomeso Evidence-based decisions require representative data

• Budget pressures increasing the need to demostrate:o Affordability of therapieso Value of therapies

• Pharmao Bringing products to market is only the first step

– Licensing ≠ approved– Licensing ≠ reimbursement– Licensing ≠ usage

o Increasing need to invest in demosntrating the value proposition for new and existing products

Population• Reversibility • Severity• Age / sex mix• Attitude to disease

• Smoke exposure• Concomitant

disease• Individual variation

in response

“real-life” population of patients

Efficacy x

Effectiveness

Clinical drivers: representative data

Clinical drivers: representative dataCriteria for selecting asthma patients to a clinical trial:o Lung function 50–80% predictedo Bronchodilator reversibilityo No co-morbiditieso Non smokers or ex-smokers <10 pack yearso Good treatment complianceo Symptomatic and regular relief medication useo Good inhaler technique

Travers et al. Thorax 2007

Norwegian study of asthma patients to identify who would be eligible for standard clinical trials

1.2%

Herland K, et al. Respir Med. 2005;99:11-9

Patient population

Does it matter if we exclude patients with:o Lesser reversibility than 20%o Active rhinitiso Smokerso Lower adherence o Poor inhaler technique

ANDo Design the study not like real-life?o Study only lasts 3 months?

Clinical drivers: representative data

Yes!

Real-life research: Is it new?

• Existing fields and terminology linked to real-life research:o Comparative effectiveness research (CER)o Epidemiology (pharmacoepidemiology)o Health economics (pharmacoeconomics)o Health policy (drug policy)o Pragmatic randomized controlled trialso Personalized medicineo Outcomes research (patient-centered

outcomes research)o Treatment “value proposition”

Evidence

Theoretical

Theoretical model provide

rationale

Classical double-blind

double-dummy RCTs

Gold standard, large range of

outcomes. But not “real-life” patients, compliance

and represent <10% of patients

Pragmatic trials

More real-life Broader

inclusion criteria Allow normal

factors to occur usually

randomised. Simple

outcomes, but still consent &

rigorous

Observational Data

Real-life patients Not randomised

Routine data Normal decisions

Difficult to ensure group comparability

Matching of case controls,

adjustment

Real-life studies

Clinical drivers: representative data

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

Contemporary View

Evidence continuum – complementary study designs

Evidence base: hierarchy—continuum

Traditional View

RCTs

Pragmatic studies

Observational studies

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

Development of guidelinesInterventionalstudies(RCT):

Efficacy

Safety

Effectiveness

Observationalstudies(pharmaco-epidemiology):

Safety

Cost-effectiveness

Effectiveness