Presentation is loading. Please wait.

Presentation is loading. Please wait.

CAMARADES: Bringing evidence to translational medicine Study Quality and Publication Bias in Experimental Stroke.

Similar presentations


Presentation on theme: "CAMARADES: Bringing evidence to translational medicine Study Quality and Publication Bias in Experimental Stroke."— Presentation transcript:

1 CAMARADES: Bringing evidence to translational medicine Study Quality and Publication Bias in Experimental Stroke

2 CAMARADES: Bringing evidence to translational medicine Presenter Disclosure Information FINANCIAL DISCLOSURE: None Malcolm Macleod PhD FRCP Study Quality and Publication Bias in Experimental Stroke UNLABELED/UNAPPROVED USES DISCLOSURE: None CONFLICT OF INTEREST DISCLOSURE: President, EuroHYP

3 CAMARADES: Bringing evidence to translational medicine interventions in experimental stroke Tested in experiments OCollins et al, 2006

4 CAMARADES: Bringing evidence to translational medicine interventions in experimental stroke Tested in focal ischaemia OCollins et al, 2006

5 CAMARADES: Bringing evidence to translational medicine interventions in experimental stroke Effective in focal ischaemia OCollins et al, 2006

6 CAMARADES: Bringing evidence to translational medicine interventions in experimental stroke Tested in clinical trial OCollins et al, 2006

7 CAMARADES: Bringing evidence to translational medicine interventions in experimental stroke Effective in clinical trial OCollins et al, 2006

8 CAMARADES: Bringing evidence to translational medicine M M

9 CAMARADES: Bringing evidence to translational medicine What is translational medicine? From: Institute of Translational Medicine, University of Texas Medical Branch

10 CAMARADES: Bringing evidence to translational medicine Animal data in stroke There are huge amounts of often confusing data Systematic review can help to make sense of it If you select extreme bits of the evidence you can prove either harm or substantial benefit However, if you have a precise and highly significant overall effect, then it is probably real Hypothermia: a systematic search identified 277 experiments in 3353 animals Better Worse Van der Worp et al, 2007

11 CAMARADES: Bringing evidence to translational medicine

12 Potential sources of bias in animal studies Internal validity External validity –Publication bias –Are the models we use good models? Co-morbidities ProblemSolution Selection BiasRandomisation Performance BiasAllocation Concealment Detection BiasBlinded outcome assessment Attrition biasReporting drop-outs/ ITT analysis

13 CAMARADES: Bringing evidence to translational medicine Internal Validity Randomisation and blinding in studies of hypothermia in experimental stroke Infarct Volume –101 publications –222 experiments –3256 animals –Improved outcome by 43.5% ( ) Blinded outcome assessment Yes No Efficacy 47%39% Randomisation 47%37% Efficacy Van der Worp et al, 2007

14 CAMARADES: Bringing evidence to translational medicine Internal Validity NXY-059 Infarct Volume –11 publications –29 experiments –408 animals –Improved outcome by 44% (35-53%) Macleod et al, 2008

15 CAMARADES: Bringing evidence to translational medicine The File Drawer problem Publication bias 0 worsebetter

16 CAMARADES: Bringing evidence to translational medicine BetterWorse Precision All outcomes – 29 publications – 109 experiments – 1596 animals – Improved outcome by 31% (27-35%) External Validity Publication Bias for FK506 Macleod et al, 2005

17 CAMARADES: Bringing evidence to translational medicine Publication bias – G-CSF England T et al 2009

18 CAMARADES: Bringing evidence to translational medicine Publication bias in experimental stroke Only 11/525 publications (2.2%) reported no significant treatment effects Trim and Fill suggested ~16% (214/1573) of experiments remain unpublished Best estimate of magnitude of problem –Observed efficacy31.3% ( ) –Adjusted efficacy 23.8% ( )

19 CAMARADES: Bringing evidence to translational medicine Publication bias RandomisationCo-morbidity bias How much efficacy is left?

20 CAMARADES: Bringing evidence to translational medicine There are many other sources of bias (Sacket, 1979) Tidying up bias Repeated peaks bias Significance bias Bogus control bias Hot stuff bias Selective reporting bias

21 CAMARADES: Bringing evidence to translational medicine Current performance against key quality items Randomisation Blinded Outcome Assessment Sample Size calculation Stroke36%29%3%

22 CAMARADES: Bringing evidence to translational medicine How does stroke compare? Randomisation Blinded Outcome Assessment Sample Size calculation Stroke36%29%3% MND31%20%<1% AD15%25%0% PD12%15%0% EAE8%15%<1% Glioma14%0%

23 CAMARADES: Bringing evidence to translational medicine Internal validity in PD models Blinded outcome assessmentComposite quality Rooke et al, submitted

24 CAMARADES: Bringing evidence to translational medicine Estimates of affinity at cannabinoid receptors McPartland et al 2007

25 CAMARADES: Bringing evidence to translational medicine Animal Studies Clinical Trial Systematic Review And Meta-analysis

26 CAMARADES: Bringing evidence to translational medicine Conclusions We could, and should, do a lot better Other diseases could do much much better Like any other process, the processes of translational medicine can be studied, systematically and methodically


Download ppt "CAMARADES: Bringing evidence to translational medicine Study Quality and Publication Bias in Experimental Stroke."

Similar presentations


Ads by Google