syrcle_rovers mini symposium sr animal studies 30082012
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Systematic reviews of clinical versus animal studies:
Parallels and challenges
Maroeska M. Rovers
Acknowledgments: Carlijn Hooijmans, Malcolm Macleod, Michael Bracken
• 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
My background
The growth in RCTs
0
5000
10000
15000
20000
25000
30000
35000
1950 1960 1970 1980 1990 2000
Year of Publication
Num
ber o
f Tria
ls /
Yea
r .
MEDLINE
Cochrane CCTR
Multicentre Trials
Systematic review in detail
Research question
Extensive literature search
Objective selection process
Critical appraisal
Objective data extraction
Synthesis of results
Structured reporting
How close is Cochrane’s 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 “questions” So 17% of questions
What about animal studies
How many systematic reviews on animal studies? 248 reviews > 7 million animal studies
“Much animal research into potential treatments for humans is wasted because it is poorly conducted and not evaluated in SRs”
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
Methodological problems
1. Heterogeneity in animal species and strains used 2. Different models of inducing illness with varying
similarity to the human condition 3. Variation in dosis/intervention schedule 4. Variability in how animals are selected 5. Loss to follow-up not reported 6. Small groups with inadequate power
Methodological problems
7. 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 inhumans
10. External validity often nog thought of
Plos. Med. 2005
Solutions: • Better powered evidence
àLarger studies or low bias meta-analyses • Registrations of studies
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