Saturday May 16th, 16.30-18.00 (MST)Altitude Room; Crowne Plaza, Denver, Colorado

REG Interstitial Lung Disease Working Group Meeting

Working Group Members

Lead: Luca Richeldi

• Bruno Crestani• Martin Kolb• Toby Maher• Francesco Bonella• Fernando J Martinez• Ganesh Raghu• Ian Glaspole• Katerina M. Antoniou• Kevin Brown• Ulrich Costabel

• Moises Selman• Thomas Geiser• Nathan Steven• Mazzei Mariano• Vincent Cottin• Demosthenes Bouros• Mona Bafadhel• Carlo Vancheri

Blue indicates confirmed attendance at the time of slide preparation

REG Supporters in attendance

Confirmed• Daniel Mcbryan• Armin Furtwaengler• Lynn Hagger• Mark Milton-Edwards• Setareh Williams• Brooke Harrow• Gokul Gopalan• Glenn Crater• Keith Allan• Paul Michael Dorinsky

• Robert Fogel• Dorothy Keininger• David Evan• Karen Mezzi• Peter Schweikert• Guilherme Safioti

Tentative / Maybe• Mark Milton-Edwards• Carlo Vancheri

Agenda

Time Item Lead

16.30-16.35 Introductions All

16.35-16.40Overview of the Respiratory Effectiveness Group

Alison Chisholm

16.40-17.45

Research Ideas Luca Richeldi

• Characterizing healthcare resource utilisation and pathway in the period prior to an ILD (or IPF) diagnosis

• Electronic lung sounds – building an audio component into early ILD diagnosis

• Evaluation in the consistency of MDT diagnoses of ILD• Other ideas from the group...?

17.45-18.00 Other Opportunities for the Group Group Discussion

A quick overview

Respiratory Effectiveness Group

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

Effect‘efficacy’ Safety

High ‘internal’ validity feasible in clear-cut trial populations

APPROVAL

Real ‘external’ validity &generalisability by mirroring

real populations and healthcare practices

Medicines won’t work if peoplecan’t or don’t take them

Needs of Regulators

Effectiveness/Outcomes

Device‘to train, or not to train’?

Adherence

CAN IT WORK IN AN IDEAL POPULATION OPTIMALLY MANAGED?

DOES IT WORK IN REAL PATIENTS MANAGED IN ROUTINE CARE

SETTINGS?

Needs of Patients, Physicians, Payers

Efficacy vs Effectiveness

• Studies have shown that efficacy RCTs exclude about 95% of asthma and 90% of COPD routine care populations due to strict inclusion criteria.1

1. Herland K, et al. Respir Med 2005;99:11–19.

Limitations: RCTs inclusions/exclusions

COPD

Asthma

Patient RCT eligibility drop-off with sequential application of standard inclusion criteria

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

What sort of evidence do we have …?P

op

ula

tio

n

Broad

Narrow

Ecology of care FreeConstrained

Highly controlled Pragmatically controlled

Observational

Managed as...

Clinical diagnosis

Confirmed diagnosis

Registration RCTs

Long term phase III

Pragmatic RCTs

Observational studies

Roche N, Price D et. al 2013 Lancet Respir Med; 1(10):e29-30

Different research questions need different research approaches to answer them…

So…? Set up REG:Our wish: To raise the quality and profile of real-life (respiratory) research so that it can be used (appropriately) to inform guidelines and management of patients in routine care.How? Through:•International collaboration •Research•Standardizing methods •Setting quality standards

& Much more…

Prior REG / UK Department of Health Collaboration

• Jones RCM, et al on behalf of REG. Lancet Respiratory Medicine. 2014; 2:267-76

• Funding by the UK Department of Health and Research in Real Life Ltd.

REG Support & Research Funding

RESEARCH IDEA GENERATION

Working Groups Identify Research Priorities in their

respective fields of expertise

SECURING FUNDING

Nature of funding dictates future study course:• Single commercial funding source: an investigator

initiated study conducted external to REG• Non-product/brand specific grant(s): an REG

Collaboration carried by REG or in partnership with REG

REG Supporters

Non-supporter& wider

institutional grants

OR

REG develops idea in

collaboration with WG /

collaborators &

seek specific research grants

REG Grants awarded at FY end

REG Core Grants Awarded to Top Priority Ideas

(subject to available funding)

Mid October Core Grant submission

deadline

Ideas prioritised by REG Research Committee

If insufficient REG Funds, continue to look externally

Agenda

Time Item Lead

16.30-16.35 Introductions All

16.35-16.40Overview of the Respiratory Effectiveness Group

Alison Chisholm

16.40-17.45

Research Ideas Luca Richeldi

• Characterizing healthcare resource utilisation and pathway in the period prior to an ILD (or IPF) diagnosis

• Electronic lung sounds – building an audio component into early ILD diagnosis

• Evaluation in the consistency of MDT diagnoses of ILD• Other ideas from the group...?

17.45-18.00 Other Opportunities for the Group Group Discussion

Where does the ILD WG Fit…?• 2014: first two (first-in-class) treatments for IPF:

o Nintedanib & pirfenidoneo Slow disease progression; do not cure or reverto NEED FOR EARLIER DIAGNOSIS

• Many forms of ILD diseases, but small prevalence of eacho Need to aggregate data…

• All patients come through primary careo Time to start looking in primary care databases…

• Need to raise awareness of ILD among primary clinicians:o Put ILD on the diagnostic “agenda” o Develop diagnostic support tools

Where to being…?Research Ideas

Idea I: Missed Diagnostic Opportunities

• There is a need to understand what happens to ILD patients before they receive their diagnosiso How and when do they engage with healthcareo What tests do they receive prior to their diagnosis?o What triggers the diagnosis?o Are there “red flags” that are being missed?

• Retrospective database study…?

Optimum Patient Care Research Database

Cohort Patients"Prevalence" within database population

Total Patient Population 2,414,621  

Asthma Population 755,693 31.30%

COPD Population 134,281 5.56%

Pulmonary fibrosis (idiopathic)

2,955 0.12%

Interstitial lung disease 5,299 0.22%

UK primary care database available to REG:

Idea II: MDT diagnostic consistency

• IPF diagnostic pathway many steps, e.g. :o Local chest clinic i.e. secondary care diagnostic

work up o X-ray o HRCT scano Lung Volume and Airflow Studies o Simple Gas Exchange Studies o Simple Lung Function o Exercise Testing (e.g. six minute walk, shuttle walk)o Lung biopsyo MDT diagnosis

But what is the variation in the diagnosis of IPF across different MDTs at different centres / different countries?

Idea III: Prospective case finding

• IPF symptomso The classic sign of IPF is fine, dry, inspiratory crackles

(“Velcro crackles”) at both bases.o The remainder of the examination is normal until disease is

advanced, at which time signs of pulmonary hypertension and right ventricular systolic dysfunction may develop.

• Respiratory Assessment:o Listening to the chest is a standard component of a

respiratory assessment.o Where is the information documented…?o Discerning changes in chest “noises” requires a standard

approach to audio assessment & recording.o Listening is “cheap”, even with electronic tools.

Idea IV & ….?

• Other ideas from the group…?

Agenda

Time Item Lead

16.30-16.35 Introductions All

16.35-16.40Overview of the Respiratory Effectiveness Group

Alison Chisholm

16.40-17.45

Research Ideas Luca Richeldi

• Characterizing healthcare resource utilisation and pathway in the period prior to an ILD (or IPF) diagnosis

• Electronic lung sounds – building an audio component into early ILD diagnosis

• Evaluation in the consistency of MDT diagnoses of ILD• Other ideas from the group...?

17.45-18.00 Other Opportunities for the Group Group Discussion

Other opportunities

Raising awareness…?

• Papers & position statements o E.g. Nature Primary Care Respiratory Medicine

• Conference symposiao Primary care respiratory conferences

– e.g. International Primary Care Respiratory Group