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Severe Asthma and Biomarkers Working Group Meeting

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Slides from meeting held at ERS 2016 in London, UK with Biomarkers and Severe Asthma REG Working Groups

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Severe Asthma and Biomarkers Working Group Meeting

  1. 1. SEVERE ASTHMA / BIOMARKERS JOINT WORKING GROUP MEETING DATE: Saturday September 3RD TIME: 14.45 –16.00 VENUE: Royal College of General Practitioners; 30 Euston Square, London, UK Co-chairs: Leif Bjermer & Rohit Katail
  2. 2. Agenda 14.45-14.50 Welcome / Introduction Leif Bjermer, Rohit Katail (Biomakers & Severe Asthma WG Leads) 14.50–14.55 On-going Biomarkers Project – GINA / NICE FeNO Editorial Kjell Alving 14.55–15.05 Severe Asthma Working Group Walter Canonica, Nikos – Motivation; Addressing a Need Papadopoulos, Rohit Katail 15.05–15.50 A Global Severe Asthma Registry a joint Biomarkers / Severe Asthma project 15.05–15.10 • REG’s potential role David Price 15.10–15.25 • What currently exists…? – Example 1: Italy (SANI) Walter Canonica – Example 2: UK Andrew Menzies-Gow 15.25–13.35 • A Global ‘Blue Print’ Victoria Carter 15.35–15.50 • Group Discussion All 15.50–16.00 Any Other Business / Open Discussion / Project Brainstorm
  3. 3. WELCOME INTRODUCTION FIRST BIOMARKERS / SEVERE ASTHMA WORKING JOINT WORKING GROUP MEETING LEIF BJERMER & ROHIT KATAIL 14.45–14.50PM
  4. 4. BIOMARKERS WORKING GROUP PROJECTS GINA/NICE FENO COMMENTARY KJELL ALVING 14.50–14.55PM
  5. 5. Differences between NICE & GINA statements on FeNO (focus on inflammometry) •  Draft developed & circulated August 2015 o  Adaptation of a letter to the Editor of ECRJ (in 2014) •  Reviewed at Biomarkers’ Working Group Meeting at the ERS (Sept 2016) •  Originally targeted at npj Primary Care Medicine o  ERS Meeting – decision to “aim higher” o  New target = Lancet Respiratory Medicine •  Formatted as a Commentary and submitted to LRM February 2016; o  Rejected: "Many thanks for submitting your manuscript to The Lancet Respiratory Medicine. Several editors here have discussed the manuscript, but their decision was that it would be better placed elsewhere.”
  6. 6. Differences between NICE & GINA statements on FeNO (focus on inflammometry) •  Formatted as Correspondence to the ERJ; submitted March 2016 •  Rejected: This letter has been assessed by external reviewers and the editorial board. Although it raises some interesting points, it was considered to add little to the debate while some other important aspects of this topic were missing. •  Reviewer 1: –  This is a very well written Letter on a timely topic in asthma –  Reads as though FeNo and blood eosinophilic counts are the only biomarkers which should be included in the guidelines for asthma management. Suggest §  Change the title in the current form, being more specific, or §  Add a table with the most promising (serum) biomarkers for asthma management, to give an idea of the complex panorama in this field. •  Reviewer 2: –  The authors initially complain that guidelines are driven by RCTs and should be driven by more real world studies. This argument does not really advance their hypothesis as we lack real world studies for the use of this technique –  There is an additional consideration of cost and availability in terms of real world implementation –  Spirometry is a poor method for assessing asthma but at least it brings well developed standards and reproducibility –  Agree with the need for more refined biomarkers for management of all airways disease but the practical aspect is the challenge of showing efficacy in RCTs and then bringing it into clinical practice. –  Refer to the most recent Cochrane review on this topic
  7. 7. Differences between NICE & GINA statements on FeNO (focus on inflammometry) •  Next…? o  Incorporate a table of promising biomarkers (as per ERJ Reviewer 1’s suggestion) –  “Reads as though FeNo and blood eosinophilic counts are the only biomarkers which should be included in the guidelines for asthma management. Suggest adding a table with the most promising (serum) biomarkers for asthma management, to give an idea of the complex panorama in this field.” o  Reformat for Respiratory Medicine
  8. 8. Developing a table of promising biomarkers •  What biomarkers should be listed in a Table – 6-8 markers? •  Any other changes / suggestions? # Biomarker Comment / Key Reference 1 ? 2 ? 3 ? 4 ? 5 ? 6 ? 7 ? 8 ?
  9. 9. REG SEVERE ASTHMA WORKING GROUP: FULFILLING AN UNMET NEED ROHIT KATAIL, NIKOS PAPADOPOULOS & WALTER CANONICA 14.55–15.05PM
  10. 10. UK News Article: Telegraph 1 Sept 2016 Asthma deaths reach highest level for decade Deaths from asthma have risen 21 per cent in a year to reach their highest figure in a decade, a charity has warned. Asthma UK said 1,468 people died from asthma attacks in the UK last year. The charity called for better implementation of digital health technology to help sufferers manage their illness. “The alarming increase in asthma deaths over the last decade is an urgent wake-up call to the Government to take action to improve standards of asthma care now,” said Kay Boycott, chief executive of Asthma UK.
  11. 11. DEVELOPING A GLOBAL SEVERE ASTHMA REGISTRY 15.05–15.50PM
  12. 12. EFPIA-EBE-VE Position on Patient Registries •  Background & Context: o  European Commission (EC) and European Medicines Agency (EMA) have supported initiatives to enhance the utility of registries. o  Recent completion of the PARENT JA, revision of Good Pharmacovigilance Practices Module VIII on PASS o  Guidance on the scientific aspects of PAES in draft o  Launch of EMA’s Patient Registries Initiative •  Principles: o  Timely to define a vision and principles regarding the development of the registry infrastructure and use of registry data to address research questions. o  There are other fundamental challenges to the successful conduct of all methods of real world evidence generation that need to be addressed.
  13. 13. EFPIA-EBE-VE Position on Patient Registries: Vision (I) •  Patient registries should be maintained as a core part of the health information infrastructure: o  Supporting healthcare systems to deliver quality care o  Providing a high quality research platform for the life science sector •  Long-term registries and networks should be established for priority diseases independently of specific product approval and reimbursement processes. •  When new medicines are launched, these patient registries, linked through international networks, should be used to address outstanding research questions of Regulators, HTA bodies, Payers and Clinicians. •  Increasing consistency, quality and therefore confidence in the evidence derived from such registries and networks should lead to greater use of registries in support of innovative, adaptive pathways of drug development, assessment, managed entry and lifecycle monitoring of benefit and risk.
  14. 14. EFPIA-EBE-VE Position on Patient Registries: Vision (II) •  The regulatory framework for the creation and maintenance of a patient registry should be defined separately from that for studies •  The creation and maintenance of a health service or disease based patient registry should not be considered a study. •  Registries that require primary data collection from patients should be classified as interventional or non-interventional consistently; if considered to be interventional, they should be designed as fixed studies rather than on-going registries. •  Clear rules for ethics approval, data privacy and consent regarding registries must be established and applied consistently across Member States.
  15. 15. EFPIA-EBE-VE Position on Patient Registries: Vision (III) •  National level patient registries should ideally be funded by healthcare systems. Industry … should be made via Public Private Partnerships wherever possible. •  Distributed health data networks should be used to connect individual registries; individual registries should be incentivised to join such networks. •  Wherever possible, individual registries should apply common standards and definitions for disease outcome data. •  There should be a clear process for researchers to access registry networks. •  The cost of research access should provide sustainable funding but not create a barrier to research. •  Specific stakeholders should define clear quality standards expected of a registry/ registry network for it to be considered suitable to address the research objectives of that stakeholder.
  16. 16. REG’s potential role: “steerage” •  Identification of •  Current registries around the world (and gaps) •  Potential national leads for a global collaboration •  Review: •  Data fields / variables within existing registries for completeness •  Develop: •  Develop a list of registry variables: •  Core: must be common to all; •  Supplementary variables: beneficial in addition to core variables, where feasible •  Algorithms to identify “Severe Asthma” patients from within existing clinical records
  17. 17. Existing registries: some examples •  Severe Asthma Network in Italy (SANI) o  G. Walter Canonica •  British Thoracic Society Severe Asthma Registry, UK o  Andrew Menzies-Gow
  18. 18. –  Observatory/Registry with a unique informa7c Pla;orm (previously tested in a Regional Network) Severe Asthma Pts in the Reference Centers Network working with the same criteria and data collec7on & possible interac7ons with similar ini7a7ves ( i.s.RASP- UK) –  Monitoring Adherence to Treatment –  Unmet Needs Scopes
  19. 19. Step 1 Recruitement GINA, SIAAIC & SIP/IRS Network of Severe Asthma Reference Centers Criteria derived from the Interna7onal Excellence Center Network (es. )
  20. 20. REFERENCE CENTERS
  21. 21. ERJ 2014 Defini7on ERS /ATS
  22. 22. MASS TARGET ASTHMA THERAPY GINA GUIDELINES TH2 HIGH TH2 LOW STRATIFIED ASTHMA PHATOGENESYs PERSONALIZED ASTHMA THERAPY Omalizumab Mepolizumab Reslizumab Dupilumab Lebrikizumab Tralokinumab Pitrakinra Brodalumab α TSLP (AMG 157) α CRTH2 PREDICTIVE BIOMARKERS of RESPONSE AIT-Allergen ImmunoTherapy ICS SABA LABA LAMA AnHLTRs OCS Chromones Macrolides Biomarkers Anrukizumab Benralizumab Ligelizumab Quilizumab Bagnasco et al. Exp.Rev.Resp.Med. 2016
  23. 23. –  DATA Collec7on for interac7on with Regulatory Authori7es & Payers –  DATA Collec7on for pharmacoeconomic evalua7ons –  DATA Collec7on & elabora7on for scien7fic pubblica7ons Scopes
  24. 24. A GLOBAL ‘BLUE PRINT’ SUPPORTING THE DELIVERY VICTORIA CARTER
  25. 25. BTS Severe Asthma Registries
  26. 26. iHARP: 5,000 pa7ents over 8 countries Chief Inves7gator: David Price UK: Henry Chrystyn, John Haughney, Dermot Ryan, Kevin Gruffydd-Jones France: Nicolas Roche, David Costa Italy: Federico Lavorini, Alberto Papi, Antonio InfanQno Spain: Miguel Román Rodríguez Sweden: Karin Lisspers, Björn Ställberg Australia: Sinthia Bosnic-AnQcevich Norway: Svein Henrichsen Netherlands: Thys van der Molen 5,000 moderate-severe asthma patients over 8 countries
  27. 27. Linking to OPCRD in the UK Clinical Trial Registries GP Demographics Questionnaire Hospital Data PrescriptionsGP Diagnostics Linking Multiple Data Sources : OPCRD Clinical Trials Registries Hasehed ID: Practice: Data:: Visit: 12345 Z0001 Inhaler Technique 05/2005 General Practitioner Patient Reported Hospital Referrals Diagnostics National Prescribing Prescriptions National Prescribing OPC Health Record 10/2010 01/2010 05/1991 04/2008 04/2008 07/2006 05/1972 05/2005 12345 Z0001 12345 12345 12345 12345 12345 12345 FeNO Reading Spiromax Prescriptions Asthma Diagnosis Ventolin 100mcg LRTI Referral RCP Symptoms High Practice Registration Poor Inhaler Technique Hashed NHS Number: 12345 Practice Code: Z0001 Yes Yes Yes Yes Yes Yes Yes Yes Visit Date: Identifier Treatment / Prescription: Consent: Hasehed ID: Practice: Data:: Visit: 12345 Z0001 Practice Details 05/1972 Hasehed ID: Practice: Data:: Visit: 12345 Z0001 Inhaler Technique 10/2010 Z0001 Spiromax Prescriptions Started 01/2010 Hasehed ID: Practice: Data:: Visit: 12345 Z0001 Asthma Diagnosis 05/1991 Hasehed ID: Practice: Data:: Visit: 12345 Z0001 Ventolin 100mcg 04/2008 Hasehed ID: Practice: Data:: Visit: 12345 Z0001 LRTI Referral 04/2008 Practice: Data:: Visit: 12345 Z0001 RCP Questions 07/2006 Hashed ID: Practice: Data:: Visit: Finding a unique iden7fier to allow linkage to various longitudinal data sources
  28. 28. Lessons from iHARP •  Strong core delivery team •  Committed specialists •  Ethics set-up: country specific •  User friendly IT interface •  Data collection & feedback •  Do not limit to cross-sectional data •  Do not re-invent the wheel
  29. 29. REG Proposal for a Global Severe Asthma Registry Key deliverables: 1)  Establishment of a global registry & standardised coding •  Containing key data (common to all contribuQng naQonal databases) on severe asthma paQents 2)  Registry set up and data collec7on •  PotenQally building on exisQng naQonal registries (such as the BTS Difficult Asthma Registry in the UK) 3)  Long-term management & oversight of the global registry •  Data pre-populaQon and linking to primary care data systems to automate/facilitate data entry
  30. 30. Dendrite Clinical Systems: Web based •  The system must be user friendly prevent duplication of data
  31. 31. Summary of Variables in the BTS Difficult Asthma Registry Follow up: Annual Review Pa7ent Details Gender, Age, Ethnicity, BMI etc Medical History ExacerbaQons, Episodes of invasive venQlaQon, Atopic disease Inves7ga7ons Eosinophils, IgE, CT Scan, Bone densitometry Lung Func7on FEV1, FVC, KCO, FENO, PC20 methacholine/histamine Allergen Tes7ng RAST posiQve, SPT posiQve, Perennial allergen etc Ques7onnaires Asthma Control QuesQonnaire (ACQ7) Euro-QOL-5D Asthma Medica7on Inhaled/oral steroids, LAMA, SABA, adherence, corQsol & prednisolone Systemic Assessment Adherence, other contribuQng factors, biologic therapy details
  32. 32. What currently exists globally?
  33. 33. Linking Primary & Secondary Care: A pilot in UK •  Using unique idenQfiers to link primary care data from OPCRD •  IdenQficaQon of severe asthma paQents managed in primary care •  Expert algorithm from REG - encouraging appropriate referrals to severe asthma clinics •  Pilot the linked data potenQal in Northern Ireland or interested UK locality (Liverpool)
  34. 34. Our Collaborative Network Observational & Pragmatic Research Institute •  600+ GP Prac7ces •  2.7 million pa,ents •  500,000 ques,onnaires •  5,000 clinical reviews •  GP research network •  OPCSD: service database Optimum Patient Care Social Enterprise Respiratory Effectiveness Group Academic Partners •  50+ Projects Delivered •  Opera,onal research capabili,es •  Commercial access to OPCRD •  Clinical trial delivery support •  Bespoke data collec,on •  Primary care specialists OPC Global Research Solutions •  140+ Publica7ons •  Interna,onal impact •  Observa,onal research •  Pragma,c clinical trials •  Sta,s,cal exper,se •  Medical writers •  Interna7onal KOL’s •  300 members •  40 countries worldwide •  14 working groups •  ADEPT ethics commiRee •  Academic access to OPCRD A group of independent companies collabora7ng together with the shared goal to improve pa7ent management and overcome unmet medical needs
  35. 35. Severe Asthma Registries Background: 5% of paQents have severe refractory asthma that responds poorly or not at all to high-dose inhaled or systemic glucocorQcosteroid treatment Aim: Define and characterise clinical phenotypes in severe asthma to facilitate research into the assessment and clinical management •  Phenotyping of paQents •  EvaluaQon and opQmizaQon of treatment •  EvaluaQon of heterogeneity in diagnosis •  IdenQficaQon of comorbidiQes •  Understanding of underlying mechanisms of airway inflammaQon & structural changes •  Development of effecQve and efficient diagnosQc rouQnes and therapeuQc principles •  Development of novel and effecQve biologic-based therapies •  GeneQc profiling of paQents with asthma
  36. 36. REG Proposal for a Global Severe Asthma Registry Key deliverables: 1)  Establishment of a global registry containing key data (common to all contribuQng naQonal databases) on severe asthma paQents •  PotenQally building on exisQng naQonal registries (such as the BTS Difficult Asthma Registry in the UK)? 2)  Registry set up and data collecQon support over Qme: •  Data pre-populaQon and linking to primary care data systems to automate/facilitate data entry 3)  Long-term management of the registry and making data available to researchers
  37. 37. OPEN TO ALL COUNTRIES: REG TO UNDERSTAND GLOBAL INTEREST A LEAD AND PILOT IN EACH COUNTRY OF AZ INTEREST: •  USA: Rohit KaQal & NJH – Severe Asthma Working Group Lead •  GERMANY : Roland Buhl – German Severe Asthma Registry (n= 463) •  UK: Liam Heaney, Andrew Menzies-Gow – UK Severe Asthma Registry (n=770) •  FRANCE: Nicolas Roche? •  ITALY: Walter Cononica – SANI •  SPAIN: Marc Miravitlles, Joan Soriano •  AUSTRALIA: Sinthia Bosnic-AnQcevich & Woolcock InsQtute REG Proposal for a Global Severe Asthma Registry
  38. 38. Apps •  PROs •  PEF etc. Medical History Severe Asthma Registry Baseline Assessment Prospec7ve Data Collec7on Smart Inhalers •  Adherence Asthma Reviews at Clinic •  Clinical assessment •  Biomarkers etc. Primary Care Records •  MedicaQon •  ExacerbaQons •  ComorbidiQes •  Healthcare resource uQlisaQon etc. Secondary Care Records •  HospitalisaQons •  Healthcare resource uQlisaQon •  QuesQonnaires •  Lung funcQon •  Biomarkers •  Allergen tesQng •  Op#onal blood sample for future gene#c tes#ng? Primary Care Records •  MedicaQon •  ExacerbaQon history •  ComorbidiQes Secondary Care Records •  HospitalisaQons •  Healthcare resource uQlisaQon REG Proposal for a Global Severe Asthma Registry
  39. 39. BENEFITS TO… Pa7ents •  PotenQal to improve paQent outcomes in short-term (through biomarker profiling and smart technologies) •  Increase understanding of severe asthma to improve paQent care in long-term Clinicians •  PaQent care: •  Improve characterisaQon (and over Qme, understanding of) severe asthma to help guide clinical decision making •  Introduce smart technologies to facilitate paQent management in clinic •  Asthma registry pre-populated from exisQng clinical systems via anonymised paQent idenQfiers (in countries where feasible) Researchers •  Access to a global registry of well-characterised severe asthma paQents •  Comprehensive retrospecQve medical history data combined with conQnued prospecQve follow-up (in countries where feasible) REG Proposal for a Global Severe Asthma Registry
  40. 40. A Working Example in the UK BTS Difficult Asthma Registry: Web Based Registry: Dendrite Clinical Systems •  770 severe asthma paQents •  Maintaining paQent anonymity and confidenQality (safe and secure) •  Time saving compared to paper-based systems •  PaQents consent to collecQon of data •  Data Controller is local hospital and Dendrite Clinical Services UK Ltd. •  UK Severe Asthma Steering Group •  REG to review UK severe asthma registry fields for global use •  Limited by cross-secQonal nature – possibility to link in with longitudinal primary care data: OPCRD
  41. 41. Linking Primary & Secondary Care: A pilot in UK •  Using pseudoanonymised unique idenQfiers (hashed NHS) to link longitudinal primary care data from OPCRD with cross- secQonal UK severe asthma registry. •  IdenQficaQon of severe asthma paQents in primary care records, using expert algorithm from REG - encouraging appropriate referral to severe asthma clinics •  Pilot the iniQaQve in Northern Ireland or interested UK locality (Liverpool)
  42. 42. Summary of Variables in the BTS Difficult Asthma Registry BASELINE Pa7ent Details •  Gender, Age, Ethnicity, BMI, etc. Medical History •  ExacerbaQons, Episodes of invasive venQlaQon, Atopic disease, etc. Inves7ga7ons •  EOS, IgE, CT scan, bone densitometry, etc. Lung Func7on •  FEV1, FVC, KCO, FeNO, PC20 methacholine/histamine, etc. Allergen Tes7ng •  RAST posiQve, SPT posiQve, PosiQve to perennial allergen, etc. Ques7onnaires •  Asthma Control QuesQonnaire (ACQ7), Euro-QoL-5D Asthma Medica7on •  Inhaled/oral steroids, LAMA, SABA, Evidence of poor adherence, CorQsol and prednisolone levels, FeNO suppression test, etc. Systema7c Assessment •  Adherence, Other factors contribuQng to symptoms, Biologic therapy details, etc. FOLLOW-UP Annual Review Bronchial Thermoplasty
  43. 43. REG Working Group Inputs •  Iden7fica7on of •  Current registries around the world (and gaps) •  PotenQal naQonal leads for a global collaboraQon •  Review: •  Data fields / variables within exisQng registries for completeness •  Develop: •  Develop a list of variables for the registries •  Core: must be common to all; •  Supplementary variables: beneficial in addiQon to core variables, where feasible •  An algorithm to idenQfy “Severe Asthma” paQents from within exisQng UK primary care clinical records
  44. 44. Timelines •  Q4 2016 •  Define core and opQmal variables •  Q1-Q2 2017 •  Set up registry within the selected sotware system •  IniQate development of infrastructure to link with other data sources, where feasible (paQent records, apps etc.) •  Q3 2017 •  Release of registry •  First paQents in pilot countries/areas •  From Q1 2018 •  Data access to researchers
  45. 45. GROUP DISCUSSION / FEEDBACK
  46. 46. ANY OTHER BUSINESS – OTHER IDEAS FOR THE GROUP(S) 15.50–16.00PM

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