SYRCLE_Rovers mini symposium sr animal studies 30082012
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SYRCLE_Rovers mini symposium sr animal studies 30082012
- 1. Systematic reviews of clinical versus animal studies: Parallels and challenges Maroeska M. Rovers Acknowledgments: Carlijn Hooijmans, Malcolm Macleod, Michael Bracken
- 2. My background โขโฏ 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 trialsโ โขโฏ 1993: founding of Cochrane Collaboration โขโฏ Mission: to enable people to make well-informed decisions about healthcare
- 4. The growth in RCTs 35000 MEDLINE 30000 25000 Number 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 Cochraneโs dream? How many reviews in Cochrane? 3,800 reviews with 6 trials each = 22,800 How many reviews are needed? A. Trials: Number of RCTs over 500,000 So 5% included so far B. Questions: Over 11,000 diseases: If 2 treatments each; 22,000 โquestionsโ So 17% of questions
- 7. What about animal studies How many systematic reviews on animal studies? 248 reviews > 7 million animal studies
- 8. โMuch animal research into potential treatments for humans is wasted because it is poorly conducted and not evaluated in SRsโ
- 9. Potential sources of bias in animal studies Bias Solution Selection bias Randomisation Performance bias Allocation concealment Detection bias Blinded outcome assessment Attrition bias ITT/ reporting drop outs
- 10. Six interventions compared: 3 similar outcomes 3 discordant results
- 11. Quality of the studies included in the SR BMJ, 2007
- 12. Consequences risk of bias Macleod et al. Stroke, 2008
- 13. Methodological problems 1.โฏ Heterogeneity in animal species and strains used 2.โฏ Different models of inducing illness with varying similarity to the human condition 3.โฏ Variation in dosis/intervention schedule 4.โฏ Variability in how animals are selected 5.โฏ Loss to follow-up not reported 6.โฏ Small groups with inadequate power
- 14. Methodological problems 7.โฏ Flawed statistical analyses (not taking into account confounding, no ITT) 8.โฏ Variety of outcomes (with uncertain relevance to human condition) 9.โฏ Length of follow-up may not correspond to disease latency inhumans 10.โฏExternal validity often nog thought of
- 16. Plos. Med. 2005 Solutions: โขโฏ Better powered evidence ร ๏ Larger studies or low bias meta-analyses โขโฏ Registrations of studies
- 17. And rememberโฆ A systematic review does NOT replace a good quality study
- 18. Future directions โขโฏ Methodology โขโฏ Search strategies โขโฏ Analyses โขโฏ Individual animal data? โขโฏ Improving experimental designs โขโฏ Real sample size calculation โขโฏ Demanding highest quality standards in conducting and reporting โขโฏ Multicenter animal studies? โขโฏ Registry of animal studies