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

CAMARADES: Bringing evidence to translational medicine 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

CAMARADES: Bringing evidence to translational medicine 43.5% protection ( ) How powerful is the treatment in animals? 101 publications 222 experiments 3256 animals

CAMARADES: Bringing evidence to translational medicine Evidence based clinical trial design Hypothermia for acute ischaemic stroke CriterionAnimal dataEuroHYP-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

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? Multi Centre Animal Studies confirm efficacy robust and monitored conduct of experiments transparent analysis and reporting deliberate heterogeneity Clinical trial

CAMARADES: Bringing evidence to translational medicine Data: More are better NXY-059 Hypothermia Cumulative meta- analysis of the efficacy of lytic treatments (eg tPA) in thrombotic animal models of stroke

CAMARADES: Bringing evidence to translational medicine Clinical trials and in vivo studies

CAMARADES: Bringing evidence to translational medicine MultiPART Multicentre Preclinical Animal Research Team

CAMARADES: Bringing evidence to translational medicine 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

CAMARADES: Bringing evidence to translational medicine 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?

CAMARADES: Bringing evidence to translational medicine Deaths from Stroke, Scotland Age 70 to 79

CAMARADES: Bringing evidence to translational medicine 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”

CAMARADES: Bringing evidence to translational medicine

Acknowledgements