REG IPF / ILD Working Group Meeting

DATE: MAY 14TH

VENUE: Westin St Francis, Union Square ROOM: Olympic Room TIME: 1:00AM-1.00PM CHAIR: Luca Richeldi, Professor of Respiratory Medicine, Chair of Interstitial Lung Disease, University of Southampton, UK

IPF/ILD WORKING GROUP MEETING

Agenda

TIME TOPIC LEAD 11.00-11.15 Study Concept / Overview Luca Richeldi

11.15-12.30 Questionnaire Development & Group Feedback

Alison Chisholm Sherry Danese

12.30-13.00

Next Steps: •  Identification of National Leads •  Questionnaire local translation /

adaptation •  Questionnaire dissemination via the

working group network •  Identifying and Addressing “missing”

global regions •  Timelines

Group; Luca (Chair)

Attendees (based pre-meeting RSVPs)

•  Aileen David Wang •  Camillo Roa •  David Price •  Simon Walsh •  Luca Richeldi •  Toby Maher •  Kevin Flaherty •  Fernando Martinez •  Sherry Danese •  Neil Barth •  Pauline Bianchi •  Mike Rosenbluth •  Hal Collard •  Kaissa de Boer

•  Arata Azuma •  Shiniti Sasak •  Kevin Brown •  Tamera Corte •  Ian Glaspole •  Bruno Crestani •  Vincent Cottin •  Manuela Funke •  Paolo Spagnolo •  Mariano Mazzei •  Silvia Quandrelli •  Pilar Rivera •  Alison Chisholm •  Thao Le

Apologies •  Carlo Vancheri •  Michael Keane •  Maria Molina Molina

Luca Richeldi (Southampton, UK) on behalf of co-Pis: Fernando Martinez (New York, USA); Kevin Flaherty (Ann Arbor, USA); Simon Walsh (Radiology; London, UK) & Jeff Myers (Pathology; Ann Arbor, USA)

Global evaluation of MDT diagnosis in the real-world

Background •  A broad survey is required to establish a picture of routine

diagnostic practice.

•  A two-phase study is proposed: o  Phase I: First characterise diagnostic practice in different

geographical areas (in terms of composition, functionality, etc.).

o  Phase II: Design a diagnostic agreement and accuracy study involving centres that reflect real-world practice (with particular interest in agreement of IPF diagnosis).

Outputs: Phase I •  Characterise the ILD diagnostic process globally,

especially in countries/territories where little is currently known.

•  Provide valuable insight as to current diagnostic practices to inform the robust design of Phase II.

•  Develop a characterised global network of ILD centres for engagement in: o  The Phase II diagnostic agreement/accuracy study o  Future ILD and IPF research (RCT and real-life studies)

Outputs: Phase II

•  Evaluate agreement and accuracy of ILD MDT diagnosis across a range of global sites and healthcare settings

•  Identify features of current MDT diagnostic practice associated with accurate diagnosis (including the effect of bronchoscopic sampling for diagnosis)

•  Produce a series of best practice recommendations to optimise the pathway to accurate ILD diagnosis for future practice.

Link with REG

•  Characterising real-world clinical practice and evaluating effectiveness (not drug efficacy)

•  REG has a proven track record in delivering real-world research on behalf of international stakeholder groups (to date primarily in asthma and COPD)

•  REG is a not-for-profit organisation; all research funding is used in the most cost-effective way possible.

Geographical Scope

•  Building on prior work,1-2 the study will include: o Dedicated and non-dedicated ILD centres o Countries within both mature and expanding

economies o All continents and key global regions.

•  Of particular interest will be features of practice in Brazil, Russia, India and China (the “BRIC” countries) owing to their limited representation in previous studies and large population size.

1.  Flaherty KR, et al. Am J Respir Crit Care Med 2004;170:904–910; 2.  Kevin R. et al. Am J Respir Crit Care Med. 2007; 175: 1054–1060.

Design: country selection (not exhaustive)

•  Inclusive approach

•  All countries and participants involved in the diagnosis of ILD eligible for inclusion

•  For operational feasibility the following continents, countries will be prioritised for inclusion.

Continent / Region Country Proposed Lead Collaborator

Europe

UK Luca Richeldi (Southampton) Italy Carlo Vancheri (Catania) France Vincent Cottin (Lyon) Germany Jürgen Behr (Munich) Greece Demosthenes Bouros (Athens) Russia Sergey Avdeev (Moscow) Scandinavia Elisabeth Bendstrup (Aarhus, Denmark) Belgium Wim Wuyts (Leuven) Netherlands Jan Grutters (Utrecht) Spain / Portugal Ferran Morell & Maria Molina Molina (Barcelona, Spain)

North America USA Kevin Flaherty (Ann Arbor) & Fernando Martinez (New York)

Canada Charlene Fell (Calgary) ± Chris Ryerson (Vancouver) ± Martin Kolb (Ontario)

South America Brazil

Ivan Rosas (Colombia) Argentina Chile

Asia

Japan Arata Azuma China Zuo Jun Xu (Beijing) India Zarir Udwadia (Bombay) Middle East Carole Youakim (Beirut, Lebanon)

The Philippines Camilo Roa, Aileen David-Wang Australasia Australia Tamara Corte (Sydney) Africa South Africa Keertan Dheda (Cape Town)

!

Design: site selection (I)

•  Lead collaborators within the prioritised countries/regions will provide local expertise on: o Geographical distribution of diagnostic centres

o Weighting of diagnostic case load across centres.

•  Through local consortia, networks and professional links, these data collection “nodes” will distribute the survey (and curate responses) within their assigned territory.*

*Industry links and the REG network will be used to engaged appropriate national leads in areas currently “unknown” to the Investigators

Design: site selection (II)

•  Pragmatic - “strategic-opportunistic” - site inclusion combining: o Scalable electronic data capture

o  Local expertise & broad participation invitation

o Representative range of (ultimately self-selecting) Participants.

Methodology •  Expertise of survey respondent: (clinical; pathology; radiology) •  Demographics of respondent site: Geographical territory

(continent, country); Practice setting: Diagnostic techniques used in practice

•  Patient demographics of respondent site: Number of (IPF and ILD) patients (i) managing and (ii) diagnosing; Referral pattern of patients

•  ILD patient management: self- / referred; # physicians seen during diagnostic pathway

•  Approach to diagnosis employed by respondent site: specialists involved; diagnostic tools used

•  Use of available therapeutics at respondent site •  Process of diagnosis: use of MDT; method of seeking specialist

input

Alison Chisholm (REG) & Sherry Danese (Outcomes Insights)

Questionnaire Development

Framing points

•  Objective & History – grew out of a desire to conduct an MDT Agreement Study

•  Differ from previous diagnostic survey work by:

Study of MDT Practice at 10 ILD Centres

Assessment of the impact of molecular diagnostics – US

centres

Question Identification

1.  Reviewed prior surveys & selected relevant questions

2.  Added questions particular to this study – structure: o  ‘About You’– i.e. respondent characterisation

o  ‘About Your Centre’ – e.g. University or Academic hospital (or not)

o  ‘About Your ILD Patients’ – e.g. Case load, Case mix, Diagnostic work up

o  ‘About Your Diagnostic Practice’ – e.g. Format, Frequency, Participants ‘Your Access to Licensed IPF therapies’ – e.g. Captures potential impact of approach to access to therapy

The ‘KISS’ Approach 1.  Keep It Simple and Short: to optimise completion rates, data quality

and ease of translation: o  Thematically grouped questions to aid in information recall o  Item reduced, e.g. removed duplicates and “nice to know” o  Reduced burden on respondents: offered categorical responses

where specific numeric responses were not key o  Avoid free text options to improve analyzability

2.  Reviewed (and further refined) by co-PIs from a clinical perspective

3.  Digitised using a customizable e-survey tool

Provisos

•  To characterize current practice around the world, but importantly: o  Inform the design of the diagnostic agreement study to

reflect the real-world and avoid bias: –  Sites / “diagnostic formats” to include –  Case mix

•  To be discussed: likely required completion by physicians

REG Survey

Please refer to accompanying survey pdf circulated with these minutes for the list of questions and question-by-question feedback

Luca Richeldi Chair & Group Discussion

Next Steps

Discussion points

•  Identification of National Leads •  Questionnaire local translation / adaptation •  Questionnaire dissemination via the working group

network •  Identifying and Addressing “missing” global

regions •  Timelines •  Others…?

Study Design Summary

Global Steering Committee Local specialist input: (i) Regional survey adaptions (ii) Geographical distribution of diagnostic centres (iii) Case load / mix distribution by centres

Approval / adaption of global methodology

Pragmatic site recruitment:

strategic, inclusive approach

Continent / Regional Lead Continent / Regional Lead Continent Lead

X X

X

X X

X

X

X

X

X

X

National Leads

Engagement of local / regional

diagnostic teams

(dedicated ILD centres

& community based)

local consortia, network and

professional links

Continent Lead

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links


Global Steering Committee Approval / adaption of global methodology


X X

X

X X

X

X

X

X

X

X

Continent Lead Local specialist input: (i) Regional survey adaptions (ii) Geographical distribution of diagnostic centres (iii) Case load / mix distribution by centres

National Leads

Geographical reach of meeting attendees

ASIA PACIFIC The Philippines •  Aileen David Wang •  Camillo Roa Singapore •  David Price •  Catherine Hutton •  Shawna Tan Japan •  Arata Azuma •  Shiniti Sasak Australia •  Tamera Corte •  Ian Glaspole(remote)

EUROPE UK •  Simon Walsh •  Luca Richeldi •  Toby Maher •  (David Price)

France •  Bruno Crestani •  Vincent Cottin Germany •  Jurgen Behr Switzerland •  Manuela Funke Italy •  Paolo Spagnolo Spain •  Pilar Rivera •  Lurdes Planas •  Joan Soriano

NORTH AMERICA USA •  Kevin Flaherty •  Fernando Martinez •  Kaissa de Boer •  Kevin Brown •  Ganesh Ragu

SOUTH AMERICA Argentina •  Mariano Mazzei Brazil •  Silvia Quandrelli Roche UK •  James Mawbray Roche Global •  Klaus BI •  Claus Justus Genentech •  Check with Thao Veracyte •  Mike Rosenbluth •  Pauline Bianchi •  Neil Barth

Continent / Region Country Proposed Lead Collaborator

Europe






Asia



!

Priority Countries & Proposed National Leads

Regional Tailoring (I) Translations: •  Google translate (most countries) FOLLOWED BY

National Lead review & revision to ensure appropriateness

•  Translations available for: o  English – UK; Esperanto; Estonian; Finnish; French; German; Greek;

Gujarati; Hebrew; Hindi; Hungarian; Italian; Japanese; Khmer; Korean; Latvian; Lithuanian; Macedonian; Mongolian; Myanmar; Norwegian; Persian; Polish; Portuguese; Romanian; Russian; Serbian; Slovak; Slovenian; Spanish (Latin America); Spanish (Spain); Swahili; Swedish; Tamil; Thai; Turkish; Ukrainian; Urdu; Vietnamese; Welsh

o  Listed in protocol, but not available for auto-translation: Philippines, China

Regional Tailoring (II)

•  Other tailoring required?

•  Mode of delivery – e-survey sufficient?


Global Steering Committee Local specialist input: (i) Regional survey adaptions (ii) Geographical distribution of diagnostic centres (iii) Case load / mix distribution by centres

Approval / adaption of global methodology

Pragmatic site recruitment:

strategic, inclusive approach


X X

X

X X

X

X

X

X

X

X

National Leads


diagnostic teams


& community based)


professional links

Continent Lead

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links

National Leads


diagnostic teams


& community based)


professional links

Dissemination Plans

Pragmatic site recruitment •  Strategic, inclusive approach

•  Utilise: o  Local consortia o  Network

–  Working Group –  REG wider collaborator group –  Supporters

o  Professional links o  Social Meida – LinkedIn;

•  Engage both: o  Dedicated ILD centres o  Community based centres

Global Coverage… gaps? Continent / Region Country Proposed Lead Collaborator

Europe






Asia



!

Key phases & timelines Study Component Indicative

Timeline

Contracts & Funding

Signing of all contracts & necessary agreements with supporting organisations and study sponsor Q4 2015

Signing of all contracts & necessary agreements with national vendors (as required) Q1 2016

Review / Adaption of Methodology

Steering Committee review & adaption of screening methodology Q1 2016

National/regional validation and/or adaptation (including translation) of screening methodology

Q2 2016

Systematic Data Collection

Commence Q3 2016

Conclude Q4 2016

Analysis Data Cleaning & master file generation Q1 2017

Analysis: full population and stratified by region Q1 2017

Publication Draft Development Q2 2017 Final manuscript submitted Q2/3 2017

Study Phase II Protocol development for Phase II analysis* Q1-Q2 2017

Commencement of Phase II Q3 2017

!

~6-months to agree methodology &

implement regional adaptions

~6-months data collection

~3-months analysis

Publication 3-6 months post analysis sign off

Phase II to commence ≤3 months of Phase I

completion

TODAY

Pause for discussion…

•  Feasibility of proposed timelines?

•  Next steps…

REG IPF / ILD Working Group Meeting

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