1. WP 8: Launching the clinical platform Workpackage 8: Determinants of antibiotic use and resistance in primary care (and definitions development) Chris Butler, Cardiff University (WP 8 leader) Theo Verheij, University of Utrecht; co-PI Paul Little, Southampton University; co-PI Herman Goossens, Project leader And the team

2. WP 8: Launching the clinical platform The ‘GRACE' Spirit 1.The Network will live on to serve science for the benefit of patients in the EU and beyond 2.Multidisciplinary; molecule to management to policy 3.Dialogue 4.Synergy

3. WP 8: Launching the clinical platform Antibiotic use and resistance Correlation between penicillin use and prevalence of penicillin non-susceptible S pneumoniae Gossens H, Lancet2005:365:579-587

4. Comparisons of national aggregate data No indications data No data on infections incidence No data on thresholds for consulting No severity data No data on outcomes Voices of patients and clinicians not heard Does not tell us what to do about the problem WP 8: Launching the clinical platform Limitations of the famous graphs

5. A GPs voice from the South Wales Valleys… You read all this literature and they do say that frequent antibiotic prescription, they develop resistance …. They say ‘oh… you are prescribing more of those antibiotics’… but then we are on the front line …it is an old mining area, a lot of them get so many chest infections here, and living in the small houses, infection is passed over so quickly … you have to treat them before it is too late … if you have not given antibiotics for a chest infection and if the patient develops pneumonia later on, you can not justify why you have not given an antibiotic …I know that I want my patient to get better quickly…our big problem is to help the hospital…we start ourselves a little bit stronger antibiotic to prevent the hospital load Butler, Simpson, Wood: submitted WP 8: Launching the clinical platform Antibiotic use and resistance

6. Improved living conditions with time Infections,complications Antibiotic Prescribing ? Aim to narrow this gap, but what is the optimal size? e.g. What about antibiotics for AECOPD in Valleys? Where is my country, region, practice? Ongoing partnership is require to ‘mind the gap’ ? WP 8: Launching the clinical platform Time, social determinants of health, prescribing, complications

7. WP 8: Launching the clinical platform Objectives 1. Establishing a primary care clinical network to serve the objectives of GRACE 2. Describe presentation, investigation, management, outcomes of community acquired LRTI in Europe 3. To describe and achieve a deep understanding of the micro-level determinants of antibiotic resistance; e.g. beliefs, knowledge, appraisals of resistance and contextual factors 4. To develop definitions for use throughout GRACE

8. WP 8: Launching the clinical platform: 1 Objective 1: Establishing the clinical platform Networks selected on basis of invitations of expressions of interest against explicit criteria

9. WP 8: Launching the clinical platform: 1 We’ve already got (a lot of) Europe covered!

10. CountryN° practices/ Co-ordinatorFacilitator N° GPs Belgium25/50 Samuel Coenen Samuel Coenen Finland5-10/50-150 Ulla-Maija Rautakorpi Ulla-Maija Rautakorpi Germany15-25/15-25 Tom Schaberg Konstanze Voigt Hungary25/20 Bernadette Kovacs Bernadette Kovacs Italy20/15 Francesco Blasi Francesco Blasi Netherlands 7/35 Theo Verheij Eelko Hak WP 8: Launching the clinical platform: 1 Networks 1

11. CountryN° practices/ Co-ordinatorFacilitator N° GPs Norway8/32Carol PascoeHasse Melbye Poland5/10 Maciek Godycki-CwirkoMaciek Godycki-Cwirko Spain20/6Jordi Almirall Jordi Almirall 15/6Antoni Torres Ruano Nuria Sanchez Sweden 10/40Bo-Eric Sigvard Mölstad Malmvall Futurum UK25/60 Christopher ButlerRichard Hibbs 8/24 Michael MooreMichael Moore WP 8: Launching the clinical platform: 1 Networks 2

12. Objective 2. Describing presentation, investigation, management and outcomes of community acquired LRTI (registration study) Each network –Minimum of 8 GP practices, 20 000 patients per network –2 x one month recruitment periods October 2006 February 2007 –150 patients per network per recruitment month –3600 LRTI patients in total at end of WP8 WP 8: Launching the clinical platform: 2

13. CRF and clinician registration form Demographics History Presentation Clinical findings Usual investigations Management Referral Perceived expectations Advice, including OTC meds, sick leave WP 8: Launching the clinical platform: 2 Clinicians

14. Diary: 28 days More detailed demographics inclusion, smoking, duration of illness, reasons for consulting, education, other household members Expectations and hopes for antibiotics Beliefs about antibiotics Reasons for consulting Daily symptoms Taking of medicines Work absence and interference with normal activities Help seeking for this illness WP 8: Launching the clinical platform: 2 Patients

15. WP 8: Launching the clinical platform: 2 General flow WP8 eligible patient goes to GP and signs informed consent GP completes registration form and CRF GP enters data into GRACE-platform Patient completes diary and sends it to NNF NNF enters diary data into GRACE-platform and tracks missing diaries and CRF’s

16. For each patient the GP receives a file with : 1.Information leaflet 2.Informed consent 3.Registration form 4.CRF 5.Diary (in local language) 6.Envelop to send diary back to NNF 7.Sticker page with patient specific study numbers WP 8: Launching the clinical platform: 2 Patient packs

17. WP 8: Launching the clinical platform: 2 Informed consent Patient goes to GP GP checks in- and exclusion criteria (e.g. cough) GP informs patient about WP8 Patient signs informed consent GP stores consent local, in patient specific file

18. WP 8: Launching the clinical platform: 2 Patient registration GP completes registration form on paper GP stores registration form local in patient specific file GP enters ASAP into GRACE-platform: Study ID, GP ID, Incl. Date, DOB and Gender GP faxes registration form to NNF

19. WP 8: Launching the clinical platform: 2 CRF GP completes CRF on paper GP enters data from CRF into GRACE-platform within 2 days GP stores CRF local in patient specific file NNF contacts GP in case of missing CRF data

20. WP 8: Launching the clinical platform: 2 Patient diary GP gives diary to patient Patient sends diary to NNF NNF contacts patient in case of missing diary Patient fills in diary (28 days) NNF contacts patient about diary 4 days after inclusion NNF enters data of diary into GRACE-platform

21. WP 8: Launching the clinical platform: 2 General flow

22. Objective 3: To describe and achieve a deep understanding of the micro-level determinants of antibiotic resistance; e.g. beliefs, knowledge, appraisals of resistance and contextual factors Qualitative study in 6 networks Second recruitment period Interviews with clinicians and patients Based on variation identified in first month of registration study, maximum variation sample of clinicians; recruit patients from those who have recently consulted with LRTI NNF to recruit and do/oversee interviews WP 8: Launching the clinical platform: 3

23. WP 8: Launching the clinical platform: 3 Why qualitative research? Generates themes that researchers may not have yet considered Generates hypotheses Gets inside the heads of the people who really matter The goal is not to find statistical validity but common or important themes

24. “I think when I was a young fiery GP trainee I used to try and not give antibiotics and now I’m softening... I’m quite well aware of the lack of firm evidence that antibiotics treat URTIs and that in terms of evidence based medicine we over prescribe antibiotics, but my own view is that I don’t really care... you're goals at the end of the consultation is for you and the mother to be satisfied.” WP 8: Launching the clinical platform: 3 An example of the power of qualitative research

25. Their perceptions of their own and others’ antibiotic prescribing Their perceptions of antibiotic resistance Barriers to change Opportunities for improvement WP 8: Launching the clinical platform: 3 Qualitative study: clinicians’ topic guide

26. Help seeking; thresholds, cultural influences Perceptions of problem of antibiotic resistance Beliefs about causes of LRTI and management Beliefs about antibiotics WP 8: Launching the clinical platform: 3 Qualitative study: patients’ topic guide

27. Training of interviewers (NNF) Translation of transcripts Integration to develop a Europe-wide, ‘grounded theory’ WP 8: Launching the clinical platform: 3 Qualitative study: process and challenges

28. Objective 4: Developing definitions Empirical research (the quantitative study will provide the platform to describe syndromes and clinical presentation) ↓ Literature searching ↓ Expert opinion to enhance the empirical research and literature searching ↓ Consensus groups (using modified Delphi technique) ↓ Face validity WP 8: Launching the clinical platform: 4

29. Finalize protocol and all materials and data collection tools: April Ethics and governance approval; April, May Site visits: May, June Pilot IT and recruitment processes: June, July Training meeting: Grace platform September First recruitment period: October 2006 (f/u Nov) Evaluation: December Second recruitment period: February 2007 (f\u March) Qualitative study: February, March 2007 WPs 9 and 10 planning WP 8: Launching the clinical platform Timetable

30. Lower respiratory tract infection is not the commonest thing managed in general practice (News, July 19) and 807 patients is a scandalous lack of evidence on which to base research, especially as the result is not what we see in hospital and general practice. Doctors taking notice of Government propaganda about not using antibiotics in the NHS have caused an increase in LRTI and death. My evidence is based on 30 years in general and hospital practice. If antibiotics don't work in LRTI perhaps these academics could explain why, when patients get an LRTI after being denied antibiotics for URTI, they get better on antibiotics in hospital. Could Professor Paul Little and his colleagues consider doing something useful.... Dr Searle, Pulse Aug 2 2004 Dr Searle, Pulse Aug 2 2004 Pulse August 2 2004 WP 8: Launching the clinical platform Why antibiotics propaganda may cause extra deaths

31. Most likely to benefit Least likely to benefit Always prescribe Uncertainty Never prescribe Physical findings Expectations of effectiveness of antibiotics Tests Perceived expectations Relationships Parents need to return to work Concern about adverse outcomes in untreated patients Duration and worsening of symptoms Physician demographics and speciality Financial/reimbursement Time Enhanced communication McFarlane, Davey WP 8: Launching the clinical platform Fill in in evidence gaps to enhance clincial practice

32. WP 8: Launching the clinical platform Multi-faceted innovation to address real problems Infrastructure innovation Integrating primary care networks across Europe Integrating primary care clinical platform with disciplines ranging from the molecular geneticists to the health economists Durable clinical platform for existing Grace studies and for new studies, Research Methods innovation Describing practice across countries, languages and health care settings Qualitative research integration across languages and settings Scientific innovation Description of variation in presentation, management and outcome Understand the variation Preparing the ground for future studies Targets for intervention Health economics and modeling studies