Evidence based translational
medicine
Clinical trial
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?
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
How powerful is the treatment
in animals?
101 publications
222 experiments
3256 animals
43.5%
protection
(40.1-47.0)
CAMARADES: Bringing evidence to translational medicine
Evidence based clinical trial design
Hypothermia 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
CAMARADES: Bringing evidence to translational medicine
CAMARADES: Bringing evidence to translational medicine
Evidence based translational
medicine
Clinical trial
Experimental Studies
Multi Centre Animal Studies
• confirm efficacy
• robust and monitored conduct of
experiments
• transparent analysis and reporting
• deliberate heterogeneity
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?
CAMARADES: Bringing evidence to translational medicine
Data: More are better
Cumulative metaanalysis of the efficacy of
lytic treatments (eg tPA)
in thrombotic animal
models of stroke
NXY-059
Hypothermia
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
Abraham Maslow
“To a man with a hammer, every problem
looks like a nail”
George Santayana
“Those who cannot remember the past are
condemned to repeat it”
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
CAMARADES: Bringing evidence to translational medicine
Acknowledgements
CAMARADES: Bringing evidence to translational medicine