SYRCLE_Rovers mini symposium sr animal studies 30082012


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SYRCLE_Rovers mini symposium sr animal studies 30082012

  1. 1. Systematic reviews ofclinical versus animal studies: Parallels and challenges Maroeska M. Rovers Acknowledgments: Carlijn Hooijmans, Malcolm Macleod, Michael Bracken
  2. 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. 3. Why so important?
  4. 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. 5. Systematic review in detail Research question Extensive Structured literature reporting search Objective Synthesis of selection results process Objective data Critical extraction appraisal
  6. 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. 7. What about animal studiesHow many systematic reviews on animal studies?248 reviews> 7 million animal studies
  8. 8. “Much animal research into potential treatments for humans is wastedbecause it is poorly conducted and not evaluated in SRs”
  9. 9. Potential sources of biasin animal studiesBias SolutionSelection bias RandomisationPerformance bias Allocation concealmentDetection bias Blinded outcome assessmentAttrition bias ITT/ reporting drop outs
  10. 10. Six interventions compared:3 similar outcomes3 discordant results
  11. 11. Quality of the studies included inthe SR BMJ, 2007
  12. 12. Consequences risk of biasMacleod et al. Stroke, 2008
  13. 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. 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. 15. Other challenges….
  16. 16. Plos. Med. 2005Solutions:•  Better powered evidence àLarger studies or low bias meta-analyses•  Registrations of studies
  17. 17. And remember… A systematic review does NOT replace a good quality study
  18. 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