Respiratory Effectiveness Group:

Steering Committee Meeting

The Arch Hotel, London 15 February, 2013 (8.30

–16.00, The Martini Library)

Meeting Objective

•

Devise an action plan!

o

Ideas:

What are we going to do?

o

Details:

How are we going to do it?

o

Priorities:

When are we going to do it?

o

Collaborations:

Who ’s going to do it?

o

Funding:

How can we make sure we can afford it?

• • • •

Morning Agenda: 8.30

–11:40

8:30 –9:00: o 9:00 –10:20: Jon: 9:00 –9:20 o o o Jerry: 9:20 –9:40 Richard: 9:40 –10:00 Leif: 10:00 –10:20: o 10:20 –10:40 Andrew: 10:40 –11:00 o o Gary: 11:00 –11:20 Marc: 11:20 –11:40 Introductions & Updates (David / Alison) Sharing Research interests Comparative effectiveness Research: an

overview from the US

Analytic hierarchy to

define priorities for effectiveness/implementation research

The RO1 NIH submission /

COPD gene group

–

potential collaborations

Real-life effectiveness of different treatment

modalities of asthma or COPD in patients with significant co-morbidities

BREAK

e-Health in COPD and asthma:

physician education tracking exacerbations, guideline dissemination and

The fallacy of asthma guidelines:

Discrepancy between science and practice The Respiratory Effectiveness Group in

COPD

11:40 –12:30 LUNCH

Afternoon Agenda: 12.30

–16.00

•

12.30

–14.30: Brainstorming how to turn the ideas into reality

•

14:30 –14:45

•

14.45

–15.30

BREAK Consolidating ideas and setting priorities

•

15.30

–16.00

•

16:00 Other business

• Future meetings • Engaging the wider group • Securing sponsorship

MEETING CLOSE

• • •

Introductions

Steering Committee

o o o o o o o o David Price Jon Campbell Richard Martin Jerry Krishnan Andrew McIvor Leif Bjermer Marc Miravitlles Gary Wong

Im plementation Manager:

Alison Chisholm

Absent Committee Members:

Christian Virchow; Guy Brusselle; Nicolas Roche; Alberto Papi; Nikos Papadopoulos; Stephen Holgate, Elliot Israel

Welcome and update

Evolving landscape: David Price What have we achieved so far: Alison Chisholm Studies underway already: David Price

8:30 –9.00

Evolving landscape: timeline

2008

•

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

2009 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 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.

2012

REG was founded!

Drivers for change: EU perspective

• • • Clinical drivers: o o On-going need to improve patient outcomes Evidence-based decisions require representative data Budget pressures increasing the need to demonstrate: o o Affordability of therapies Value of therapies Pharma o Bringing products to market is only the first step – – –

Licensing ≠ approved Licensing ≠ reimbursement Licensing ≠ usage

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

Clinical drivers: representative data

• • • •

Population

Reversibility Severity Age / sex mix Attitude to disease • • • Smoke exposure Concomitant disease Individual variation in response Efficacy x “real-life” population of patients

Effectivenes s

Clinical drivers: representative data

Criteria for selecting asthma patients to a clinical trial: o Lung function 50 –80% predicted o Bronchodilator reversibility o No co-morbidities o Non smokers or ex-smokers <10 pack years o Good treatment compliance o Symptomatic and regular relief medication use o 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%

Patient population

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

Clinical drivers: representative data

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

AND

o Design the study not like real-life?

o Study only lasts 3 months?

Clinical drivers: representative data

Evidence

Theoretical Theoretical model provide rationale Classical double blind double dummy RCTs Pragmatic trials Observational Data Gold standard, large range of outcomes.

But not “real life” patients, compliance and represent <10% of patients More real-life Broader inclusion criteria Allow

Real-life studies

occur usually Not randomised Difficult to ensure randomised. Real-life patients group comparability Simple outcomes, Matching of case but still consent & controls, rigorous adjustment

Evidence base: hierarchy —continuum

Evidence continuum – complementary study designs

RCTs

RCTs Pragmatic Observational trials

Pragmatic studies

Experiment, observation, mathematics, individually and

studies

collectively, have a crucial role in providing the evidential basis

Observational studies

should be replaced by accepting Hierarchies of evidence – indeed embracing – a diversity of approaches.

Sir Michael Rawlins, Head of NICE, Lancet 2008

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

Commercial drivers…

• Drugs must be shown to: o Be safe o Be efficacious o Address an unmet clinical need

But also to be:

o Cost-effective o Affordable o …“value propositions”

Development of guidelines

Interventional studies (RCT): Efficacy Safety Effectiveness Observational studies

(pharmaco epidemiology):

Safety Cost effectiveness Effectiveness

The future of drug research

• • Multiple rich heterogeneous and intricately constructed ‘real world ’ data sets of Electronic Medical Records and Transactional Claims databases o Surveillance approaches are now being innovatively applied to such data o Several international initiatives and partnerships doing essential foundational work in the field o Challenging how to determine how to best utilise this wealth of data, and how to best incorporate such analyses into overall safety strategies Analysis of real world data is only one potential component of an overall continual assessment of risk benefit

However… there are challenges

Obstacle

No standard methods or endpoints Concerns around internal validity and confounding of results

Solution?

Carry out validation studies Set standards Enforce minimum planning by offering study registration Match patients Explore different matching methods; set gold standard Promote and facilitate a priori study registration Cynicism around retrospective data mining Limited understanding of how to interpret the data Educate and raise awareness Limited penetration of the data: – to high impact journals – clinical guidelines Address the issues above, and the data will start to talk for itself…?

Set up REG  an international, collaborative approach