8 February 2012, 12:30-13:10

1. A journey into bioclinical evidence: from bench... to bedside... to population Giuseppe Biondi Zoccai gbiondizoccai@gmail.com 8 February2012, 12:30-13:10

2. Learning goals • Goals of bioclinical research and evidence hierarchy • Primary research • Secondary research

3. Why collaboration is needed? CLINICIAN BASIC SCIENTIST

4. How to implement collaboration

5. Learning goals • Goals of bioclinical research and evidence hierarchy • Primary research • Secondary research

6. Goals of bioclinical research • Increase knowledge • Improve decision making • Improve process efficiency • Improve clinical outcomes These goals are (hopefully) fulfilled by accumulating bioclinical evidence

7. Final aim is causal inference

8. Final aim is causal inference • Does the association make biological sense? • Is there a dose-response gradient? • Is the temporal association correct? • Is the association specific? • Is there evidence from true experimentation in humans? • Is the association strong? • Is the association consistent from study to study? Sir Austin Bradford Hill

9. What about evidence-based medicine?

10. What about evidence-based medicine? Excerptfrom a 1990 leafletforinternal medicine resident at McMasterUniversity(Hamilton, Canada): “…goalofevidence-based medicine is tobeawareof the evidence on whichone’s practice is based, the soundnessof the evidence, and the strengthofinference the evidencepermits. The strategyemployedrequires a cleardelineationof the relevantquestion(s); a thoroughsearchof the literaturerelatingtoquestions; a criticalappraisalof the evidence, and itsapplicabilityto the clinical situation; and a balancedapplicationof the conclusionsto the clinicalproblem.” Guyatt and Rennie, Users’ guide to the medical literature, 2002

11. Evidence-based medicine (EBM) Definition: The coscientious, explicit, and judicioususeofcurrent best evidence in makingdecisionsabout the care ofindividualpatients. The practiceofevidence-based medicine requiresintegrationofindividualclinical expertise and patientpreferenceswith the best availableexternalclinicalevidencefromsystematicsearch. Guyatt and Rennie, Users’ guide to the medical literature, 2002

12. Rebuttal to critics of EBM Evidence alone is never sufficient to make a clinical decision: decision makers must always trade the benefits and risks, inconvenience, and costs associated with alternative management strategies, and in doing so consider the patient’s values! Guyatt and Rennie, Users’ guide to the medical literature, 2002

13. EBM hierarchy of evidence • N of 1 randomized controlled trial • Systematic reviews of randomized trials • Single randomized trial • Systematic review of observational studies addressing patient-important outcomes • Single observational study addressing patient-important outcomes • Physiologic studies (eg blood pressure, cardiac output, exercise capacity, bone density, and so forth) • Unsystematic clinical observations • Non-clinical studies Guyatt and Rennie, Users’ guide to the medical literature, 2002

14. Other evidence hierarchies Evans, J Clin Nurs 2003

15. Learning goals • Goals of bioclinical research and evidence hierarchy • Primary research • Secondary research

16. Bench: in vitro study Nührenberg et al, Cardiovasc Res 2008

17. Bench: animal study Abbate et al, Circulation 2008

18. Bedside: case report Biondi-Zoccai et al, Catheter Cardiovasc Interv 2011

19. Bedside: case series Biondi-Zoccai et al, Int J Cardiol 2007

20. Bedside: cross-sectionalstudy Herrington et al, Circulation 2004

21. Bedside: cohort study (registry) Sangiorgi et al, EuroIntervention 2007

22. Bedside: case-controlstudy Guagliumi et al, J Am Coll Cardiol Intv 2012

23. Bedside: non-randomized cohort study Biondi-Zoccai et al, Clin Res Cardiol 2011

24. Bedside: therapeuticrandomizedtrial Biondi-Zoccai et al, Acta Cardiol 2011

25. Bedside: diagnosticrandomized trial Ouwendijk et al, ARJ 2008

26. Learning goals • Goals of bioclinical research and evidence hierarchy • Primary research • Secondary research

27. Parallel hierarchy of CV research Qualitative reviews Case reports and series Observational studies Systematic reviews Observational controlled studies Meta-analyses from individual studies Randomized controlled trials Meta-analyses from individual patient data Multicenter randomized controlled trials Biondi-Zoccai et al, Ital Heart J 2003

28. Meta-analyses can bridge the gap • What is a systematic review? • A systematic appraisal of the methodological quality, clinical relevance and consistency of published evidence on a specific clinical topic in order to provide clear suggestions for a specific healthcare problem • What is a meta-analysis? • A quantitative synthesis that, preserving the identity of individual studies, tries to provide an estimate of the overall effect of an intervention, exposure, or diagnostic strategy Biondi-Zoccai et al, HSR Proceedings in Anesthesia and Intensive Care 2011

29. Bench: qualitative review Dinarello, Cancer Metastasis Rev 2010

30. Animal research meta-analyses are feasible and fundable http://www.nc3rs.org.uk/page.asp?id=864

31. Bench: study level systematic review and meta-analysis Biondi-Zoccai et al, Rescuscitation 2003

32. Bedside: qualitative review Romagnoli et al, JACC Int 2008

33. Bedside & population: systematic review (without meta-analysis) Kip et al, JACC 2008

34. Bedside & population: study level meta-analysis Agostoni et al, JACC 2004

35. Bedside & population: individual patient levelmeta-analysis Burzotta et al, Eur Heart J 2009

36. Bedside & population: network meta-analysis with mixed treatment comparison Palmerini et al, submtted

37. Take home messages • Accumulation of bioclinical evidence is a collective and cumulative effort • No hypothesis or project is good or bad at beginning, but may well or badly planned • Constructive collaboration between basic scientists and clinical researchers is pivotal to succeed • In my humble opinion, the best researchers are probably those who can demonstrate their ideas were wrong (à la Karl Popper)

38. Thank you for your attentionFor any correspondence: gbiondizoccai@gmail.comFor these and further slides on these topics feel free to visit the metcardio.org website:http://www.metcardio.org/slides.html