Respiratory Effectiveness Group: Steering Committee MeetingThe Arch Hotel, London15 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: Introductions & Updates (David /

Alison)

• 9:00–10:20: Sharing Research interests o Jon: 9:00–9:20 Comparative effectiveness Research: an

overview from the USo Jerry: 9:20–9:40 Analytic hierarchy to define priorities for

effectiveness/implementation researcho Richard: 9:40–10:00 The RO1 NIH submission / COPD gene group –

potential collaborationso Leif: 10:00–10:20: Real-life effectiveness of different treatment

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

• 10:20–10:40 BREAKo Andrew: 10:40–11:00 e-Health in COPD and asthma:

trackingexacerbations, guideline dissemination and physician education

o Gary: 11:00–11:20 The fallacy of asthma guidelines: Discrepancy between science and practice

o Marc: 11:20–11:40 The Respiratory Effectiveness Group in COPD

• 11:40–12:30 LUNCH

Afternoon Agenda: 12.30–16.00

Introductions• Steering Committee

o David Priceo Jon Campbello Richard Martino Jerry Krishnano Andrew McIvor o Leif Bjermero Marc Miravitlleso Gary Wong

• Implementation Manager: Alison Chisholm

• Absent Committee Members:

Christian Virchow; Guy Brusselle; Nicolas Roche; Alberto Papi;

Nikos Papadopoulos; Stephen Holgate, Elliot Israel

Welcome and updateEvolving landscape: David Price What have we achieved so far: Alison ChisholmStudies underway already: David Price

8:30–9.00

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 demonstrate: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 demonstrating the value proposition for new and existing products

“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

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

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 safeo Be efficaciouso Address an unmet

clinical need

But also to be:o Cost-effective o Affordableo …“value propositions”

Development of guidelinesInterventionalstudies(RCT):

Efficacy

Safety

Effectiveness

Observationalstudies(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 Solution?

No standard methods or endpoints

Carry out validation studiesSet standardsEnforce minimum planning by offering study registration

Concerns around internal validity and confounding of results

Match patientsExplore different matching methods; set gold standard

Cynicism around retrospective data mining

Promote and facilitate a priori study registration

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