8 February 2012, 12:30-13:10

A journey into bioclinical evidence: from bench...

to bedside... to population

Giuseppe Biondi Zoccaigbiondizoccai@gmail.com

Learning goals

• Goals of bioclinical research and evidence hierarchy

• Primary research

• Secondary research

Why collaboration is needed?

CLINICIAN

BASIC SCIENTIST

How to implement collaboration

Learning goals

• Goals of bioclinical research and evidence hierarchy

• Primary research

• Secondary research

Goals of bioclinical research

• Increase knowledge

• Improve decision making

• Improve process efficiency

• Improve clinical outcomes

These goals are (hopefully) fulfilled by accumulating bioclinical evidence

Final aim is causal inference

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

What about evidence-based medicine?

What about evidence-based medicine?

Excerpt from a 1990 leaflet for internal medicine resident at McMaster University (Hamilton, Canada):

“…goal of evidence-based medicine is to be aware of the evidence on which one’s practice is based, the soundness of the evidence, and the strength of inference the evidence permits.

The strategy employed requires a clear delineation of the relevant question(s); a thorough search of the literature relating to questions; a critical appraisal of the evidence, and its applicability to the clinical situation; and a balanced application of the conclusions to the clinical problem.”

Guyatt and Rennie, Users’ guide to the medical literature, 2002

Evidence-based medicine (EBM)

Definition:

The coscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.

The practice of evidence-based medicine requires integration of individual clinical expertise and patient preferences with the best available external clinical evidence from systematic search.

Guyatt and Rennie, Users’ guide to the medical literature, 2002

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

EBM hierarchy of evidence1. N of 1 randomized controlled trial

2. Systematic reviews of randomized trials

3. Single randomized trial

4. Systematic review of observational studies addressing patient-important outcomes

5. Single observational study addressing patient-important outcomes

6. Physiologic studies (eg blood pressure, cardiac output, exercise capacity, bone density, and so forth)

7. Unsystematic clinical observations

8. Non-clinical studiesGuyatt and Rennie, Users’ guide to the medical literature, 2002

Other evidence hierarchies

Evans, J Clin Nurs 2003

Learning goals

• Goals of bioclinical research and evidence hierarchy

• Primary research

• Secondary research

Bench: in vitro study

Nührenberg et al, Cardiovasc Res 2008

Bench: animal study

Abbate et al, Circulation 2008

Biondi-Zoccai et al, Catheter Cardiovasc Interv 2011

Bedside: case report

Bedside: case series

Biondi-Zoccai et al, Int J Cardiol 2007

Bedside: cross-sectional study

Herrington et al, Circulation 2004

Bedside: cohort study (registry)

Sangiorgi et al, EuroIntervention 2007

Bedside: case-control study

Guagliumi et al, J Am Coll Cardiol Intv 2012

Bedside: non-randomized cohort study

Biondi-Zoccai et al, Clin Res Cardiol 2011

Bedside: therapeutic randomized trial

Biondi-Zoccai et al, Acta Cardiol 2011

Bedside: diagnostic randomized trial

Ouwendijk et al, ARJ 2008

Learning goals

• Goals of bioclinical research and evidence hierarchy

• Primary research

• Secondary research

Parallel hierarchy of CV research

Biondi-Zoccai et al, Ital Heart J 2003

Qualitative reviews

Systematic reviews

Meta-analyses from individual studies

Meta-analyses from individual patient data

Case reports and series

Observational studies

Observational controlled studies

Randomized controlled trials

Multicenter randomized controlled trials

Meta-analyses can bridge the gap

Biondi-Zoccai et al, HSR Proceedings in Anesthesia and Intensive Care 2011

• 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

Bench: qualitative review

Dinarello, Cancer Metastasis Rev 2010

Animal research meta-analyses are feasible and fundable

http://www.nc3rs.org.uk/page.asp?id=864

Bench: study level systematic review and meta-analysis

Biondi-Zoccai et al, Rescuscitation 2003

Bedside: qualitative review

Romagnoli et al, JACC Int 2008

Bedside & population: systematic review (without meta-analysis)

Kip et al, JACC 2008

Bedside & population: study level meta-analysis

Agostoni et al, JACC 2004

Bedside & population: individual patient level meta-analysis

Burzotta et al, Eur Heart J 2009

Bedside & population: network meta-analysis with mixed treatment comparison

Palmerini et al, submtted

• 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)

Take home messages

Thank you for your attention

For any correspondence: gbiondizoccai@gmail.com

For these and further slides on these topics feel free to visit the metcardio.org website:

http://www.metcardio.org/slides.html