camarades: bringing evidence to translational medicine evidence based translational medicine...

CAMARADES: Bringing evidence to translational medicine

Evidence based translational medicine

Experimental Studies

Systematic review and meta-analysis • how powerful is the treatment?• what is the quality of evidence?• what is the range of evidence?• is there evidence of a publication bias?• What are the conditions of maximum efficacy?

Clinical trial


Cooling for stroke

• Cooling seems to work in patients who have brain injury due to cardiac arrest

• There’s lots of stories about individual patients who should have extensive brain damage but don’t

• Many labs use cooling as a positive control in their animal studies

• Preliminary evidence from clinical trials in stroke is encouraging


43.5% protection(40.1-47.0)

How powerful is the treatment in animals?

101 publications222 experiments3256 animals


Evidence based clinical trial designHypothermia for acute ischaemic stroke

Criterion Animal data EuroHYP-1

How powerful is the treatment?

>40% improvement in outcome

Powered to detect 7% improvement in outcome

What is the quality of evidence?

Efficacy maintained in high quality studies

Randomised, blinded outcome assessment, intensely monitored

Is there evidence of a publication bias?

Yes, but >35% improvement in adjusted outcome

Registered

What is the range of evidence?

Good: duration of cooling, delay to treatment, intensity, hypertension, reperfusion

Patients >18yo with moderate to severe stroke treated within 6 hrs

What are the conditions of maximum efficacy?

Temperature dependent: otherwise robust across dimensions

Target 34-35°C


Evidence based translational medicine

Experimental Studies

Systematic review and meta-analysis • how powerful is the treatment?• what is the quality of evidence?• what is the range of evidence?• is there evidence of a publication bias?• What are the conditions of maximum efficacy?

Multi Centre Animal Studies• confirm efficacy• robust and monitored conduct of

experiments• transparent analysis and reporting• deliberate heterogeneity

Clinical trial


Data: More are better

NXY-059NXY-059

HypothermiaHypothermia

Cumulative meta-analysis of the efficacy of lytic treatments (eg tPA) in thrombotic animal models of stroke


Clinical trials and in vivo studies


MultiPARTMulticentre Preclinical Animal Research Team


What we’ve found out so far …

• Animal studies which do not report simple measures to avoid bias give larger estimates of how good drugs are

• Most animal studies do not report simple measures to reduce bias

• Publication and selective outcome reporting biases are important and prevalent

• You cannot assume rigour, even in Journals of “impact”• You can only find these things out by studying large

numbers of studies


What we’re looking into now…

• Can we advise scientists on more efficient research design?• Can we use this approach better to understand animal

models of mental illness?• Can we automate some of the techniques required?• Can we help publishers improve quality?• 3000 publications are added to PubMed each day– can we

build tools to provide up-to-date research summaries?• Can we use this approach to design better clinical trials?


Deaths from Stroke, ScotlandAge 70 to 79


George Santayana

“Those who cannot remember the past are condemned to repeat it”

Abraham Maslow

“To a man with a hammer, every problem looks like a nail”

Karl Marx

“Hegel said somewhere that history tends to repeat itself. He forgot to add that the first time is tragedy, the second is farce”


Acknowledgements

camarades: bringing evidence to translational medicine evidence based translational medicine...

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