SYRCLE_Hooijmans mini symposium sr animal studies 30082012

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SYRCLE_Hooijmans mini symposium sr animal studies 30082012

  1. 1. What does it take to perform aSystematic Review of animal studies? Carlijn Hooijmans C.Hooijmans@cdl.umcn.nl Central Animal Laboratory, SYstematic Review Centre for Laboratory animal Experimentation; SYRCLE Radboud University Medical Centre www.umcn.nl/SYRCLE 1
  2. 2. Systematic steps:1. Phrase the research question2. Define in- and exclusion criteria3. Search systematically for ALL original papers4. Select relevant papers5. Assess study quality and validity6. Extract data7. Analyze results (when possible perform MA)8. Interpret and present data 2
  3. 3. Focus of this presentation:1. Phrase the research question2. Define in- and exclusion criteria3. Search systematically for ALL original papers4. Select relevant papers5. Assess study quality and validity6. Extract data7. Analyze results (when possible perform MA)8. Interpret and present data 3
  4. 4. Focus of this presentation:1. Phrase the research question2. Define in- and exclusion criteria3. Search systematically for ALL original papers4. Select relevant papers5. Assess study quality and validity6. Extract data7. Analyze results (when possible perform MA)8. Interpret and present data 4
  5. 5. Goal of Searching systematically• Detect the maximum amount of available information Advantages of Searching systematically• Prevent false or imprecise conclusions• Prevent unnecessary experimentation• Obtain new insights that may arise from aggregating earlier work 5
  6. 6. How to search systematically?• Formulate adequate and specific research question  Define: - Disease of interest/ health problem - Population - Intervention/exposure - Outcome measures  Example: „What is the effect of [intervention/exposure] on [outcome measures] in [population studied] for [disease of interest/health problem]?• Identify appropriate databases• Create and run a comprehensive search strategy 6
  7. 7. How to search systematically?• Transform research question into search strategy for PubMed  Critical search components (SC).• Identify relevant search terms for each SC. o Identify Medical Subject Headings (MeSH) terms "fatty acids, omega-3"[MeSH Terms] o Identify free-text terms (synonims) Fish oil [tiab], Omega-3 [tiab] , PUFAs [tiab], DHA [tiab], EPA [tiab], omega 3 fatty acids [tiab], omega 3 fatty acid [tiab], polyunsaturated fatty acids [tiab] etc….. o Combine MeSH terms and free-text terms "fatty acids, omega-3"[MeSH Terms] OR Fish oil [tiab] OR Omega-3 [tiab] OR, PUFAs [tiab] OR etc• Repeat step 1-3 for every SC• Combine SCs 7
  8. 8. Example: Systematic Review about supplementation of omega-3fatty acids in animal models for Alzheimer’s DiseaseQuick search in PubMed: 8
  9. 9. Example: Systematic Review about supplementation of omega-3fatty acids in animal models for Alzheimer’s Disease Comphrensive search strategy in PubMed:Omega-3Alzheimer‟sAnimal models 9
  10. 10. More information about searchingsystematically and finding all animal studies? 10
  11. 11. Focus of this presentation:1. Phrase the research question2. Define in- and exclusion criteria3. Search systematically for ALL original papers4. Select relevant papers5. Assess study quality and validity6. Extract data7. Analyze results (when possible perform MA)8. Interpret and present data 11
  12. 12. Why should we critically appraise the included papers?• Low methodological quality often causes bias in the study results  overestimation or underestimation Macleod et al. Stroke, 2008 12
  13. 13. Why should we critically appraise the included papers?• The conclusions resulting from a SR/meta-analysis are dependent of the quality of the original included studies  Transparancy >>>> improves interpretation/reliability  Invalid studies may produce misleading results Garbage in = garbage out 13
  14. 14. How do we critically appraise the included papers?• 2 dimensions: External validity Internal validity• External validity:  Generalizability of the study results• Internal validity:  The extent to which the results of a study are correct for the circumstances being studied (methodological quality)  Threatened by bias (systematic errors) 14
  15. 15. How do we critically appraise the included papers?Type of bias Description SolutionSelection bias: Systematic differences between baseline Randomization characteristics of the groups that are comparedPerformance Systematic differences between groups Allocation concealmentbias: in the care or in exposure to factors other than the intervention of interestDetection bias: Systematic differences between groups in Blinding how outcomes are determinedAttrition bias: Systematic differences between groups in Reporting drop outs “drop outs” from a study (reason and nr) 15
  16. 16. How do we critically appraise the included papers? 0% 20% 40% 60% 80% 100% 1) Was it stated in the method section that the experiment was randomized? 2) In case the answer at 1) was yes: Was the method of randomization adequate? 2) In case the answer at 1) was no: Were the groups similar at baseline? 3) Was the allocation to the different groups during the randomization process concealed? 4) Were the caregivers blinded for the allocation of the animals to the specific groups 5) Was the outcome assessment blinded? 6) Methods for outcome assessment the same in both groups? 7) Is the timing of the intervention during the day similar in both groups? 8) Was the outcome assessment randomized across the groups? 9) Number of excluded animals specified per experimental group for each outcome measure? 10) Reason for exclusion mentioned for each excluded animal? yes no unclear naYes=Low risk of bias. No= High risk of bias. ?=Unclear risk of bias. N.a.=not applicable 16
  17. 17. 17
  18. 18. Focus of this presentation:1. Phrase the research question2. Define in- and exclusion criteria3. Search systematically for ALL original papers4. Select relevant papers5. Assess study quality and validity6. Extract data7. Analyze results (when possible perform MA)8. Interpret and present data 18
  19. 19. Why conducting meta-analyses?• To increase power• To increase the precision of estimates of treatment effects• To obtain new information about safety and efficacy of treatments that is not directly visible in the individual studies• To generate new hypothesis 19
  20. 20. How to conduct a meta-analyses?Cell death Data from individual studies Adapted data for MA Experimental group Control group measure mean sd n mean sd n effect effect size (confidence interval) Study A % 1.71 -0.05 6 1,9 0,07 5 significant -2.91 [-4.83, -0.98] Study B ng/ml 104 -6.29 6 114 6,28 6 significant -1.51 [-2.86, -0.16] Study C % 1 -0.17 12 1,3 0,35 12 significant -1.05 [-1.92, -0.19] Study D nr of cells -241 14,7 8 -233 17,8 7 not significant -0.50 [-1.53, 0.54] Study E nr of cells -190 15,1 6 -168 17,6 7 significant -1.24 [-2.47, -0.01] Study F nr of cells -161 14,6 7 -181 10,3 7 not significant -0.19 [-1.24, 0.86] Overall -1.02 [-1.61, -0.43] -5 0 +5 20
  21. 21. Subgroup analyses (fictive dataset) Overall -1.47 [2.33, -0.61] 21
  22. 22. Subgroup analyses (fictive dataset) Overall -1.47 [2.33, -0.61] Males -0.79 [-1.51, -0.06] Females -3.64 [-4.78, -2.50] 22
  23. 23. Subgroup analyses (fictive dataset) Overall -1.47 [2.33, -0.61] Males -0.79 [-1.51, -0.06] Females -3.64 [-4.78, -2.50] Hippocampus -1.92 [-2.65, -1.19] Cortex 0.37 [-0.24, 0.98] 23
  24. 24. Subgroup analyses (fictive dataset) Overall -1.47 [2.33, -0.61] Males -0.79 [-1.51, -0.06] Females -3.64 [-4.78, -2.50] Hippocampus -1.92 [-2.65, -1.19] Cortex 0.37 [-0.24, 0.98] 24
  25. 25. So we discussed:1. Phrase the research question2. Define in- and exclusion criteria3. Search systematically for ALL original papers4. Select relevant papers5. Assess study quality and validity6. Extract data7. Analyze results (when possible perform MA)8. Interpret and present data 25
  26. 26. Narrative review versus systematic reviewFeature Narrative review Systematic reviewResearch Often unclear or broad Specified and specificquestionSources and Not usually specified Comprehensive and explicitsearch search strategy. More than 1 database.Study Not usually specified Explicit selection criteriaselectionRisk of bias Not usually present or only Critical appraisal on the basisassessment implicit of explicit criteriaData Often a qualitative summary Often also a quantitativesynthesis summary (meta-analysis) 26
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