SYRCLE_Rovers mini symposium sr animal studies 30082012
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  • 1. Systematic reviews ofclinical versus animal studies: Parallels and challenges Maroeska M. Rovers Acknowledgments: Carlijn Hooijmans, Malcolm Macleod, Michael Bracken
  • 2. My background•  Archie Cochrane in 1979: "It is surely a great criticism of our profession that we have not organised a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomised controlled trials”•  1993: founding of Cochrane Collaboration•  Mission: to enable people to make well-informed decisions about healthcare
  • 3. Why so important?
  • 4. The growth in RCTs 35000 MEDLINE 30000 25000Number of Trials / Year . 20000 Cochrane CCTR 15000 10000 5000 Multicentre Trials 0 1950 1960 1970 1980 1990 2000 Year of Publication
  • 5. Systematic review in detail Research question Extensive Structured literature reporting search Objective Synthesis of selection results process Objective data Critical extraction appraisal
  • 6. How close is Cochrane’s dream?How many reviews in Cochrane?3,800 reviews with 6 trials each = 22,800How many reviews are needed?A. Trials: Number of RCTs over 500,000 So 5% included so farB. Questions: Over 11,000 diseases: If 2 treatments each; 22,000 “questions” So 17% of questions
  • 7. What about animal studiesHow many systematic reviews on animal studies?248 reviews> 7 million animal studies
  • 8. “Much animal research into potential treatments for humans is wastedbecause it is poorly conducted and not evaluated in SRs”
  • 9. Potential sources of biasin animal studiesBias SolutionSelection bias RandomisationPerformance bias Allocation concealmentDetection bias Blinded outcome assessmentAttrition bias ITT/ reporting drop outs
  • 10. Six interventions compared:3 similar outcomes3 discordant results
  • 11. Quality of the studies included inthe SR BMJ, 2007
  • 12. Consequences risk of biasMacleod et al. Stroke, 2008
  • 13. Methodological problems1.  Heterogeneity in animal species and strains used2.  Different models of inducing illness with varying similarity to the human condition3.  Variation in dosis/intervention schedule4.  Variability in how animals are selected5.  Loss to follow-up not reported6.  Small groups with inadequate power
  • 14. Methodological problems7.  Flawed statistical analyses (not taking into account confounding, no ITT)8.  Variety of outcomes (with uncertain relevance to human condition)9.  Length of follow-up may not correspond to disease latency inhumans10. External validity often nog thought of
  • 15. Other challenges….
  • 16. Plos. Med. 2005Solutions:•  Better powered evidence àLarger studies or low bias meta-analyses•  Registrations of studies
  • 17. And remember… A systematic review does NOT replace a good quality study
  • 18. Future directions•  Methodology •  Search strategies •  Analyses •  Individual animal data?•  Improving experimental designs •  Real sample size calculation •  Demanding highest quality standards in conducting and reporting •  Multicenter animal studies?•  Registry of animal studies