Meta Analysis Meta Analysis

Meta Analysis A family of (statistical) procedures used to combine or compare results of multiple studies
Analysis of Research • Primary : original analysis of data • Secondary : re­analysis of old data • Meta­ : analysis of analyses (Systematic Review)
“ Vote Counting Vote Counting ” ” An Example (Treat A vs Treat B): • 100 studies n=30 each • if medium effect size (will discuss) • then 33% (p<.05) 67% (NS) • conclusion: not significant (x wrong!) • hence, no “vote counting”
Hypothetical Example A B C D Con n mean 41 11 29 225 104 9 11 23 Exp n mean t 41 17 2.72 ** 33 175 ­1.95 98 12 2.03 * 11 31 1.56 Note : very different means (diff instruments?)
Calculation Steps t df 1­sided p A 2.72 80 B ­1.95 60 C 2.03 200 D 1.56 20 S 4.36 Z ­2 log e p .004 2.65 .972 ­1.91 .022 2.02 .067 1.50 11.04 0.06 7.65 5.40
4.26 24.15
Combined Test Fisher :­­ chi­sq = ­2 S log e p df = 2 n where p : 1­sided p­value in each test n : number of tests
Results Fisher : chisq = 24.15 df = 2 x 4 = 8 p = 0.0022 Stouffer : Z = 4.26 / sqrt (4) = 2.13 p = 0.0332 Winer : Z = 4.36 / sqrt [(80/78) + …+(20/18)] = 2.13 p = 0.0332
Questions • Weighting ? e.g. sample size ? • Measure of significance => p­value • Measure of magnitude => ???? i.e, degree null hypothesis rejected ???
The Hypothetical Example Con Exp ES = M 1 M 2 sd (M 2 ­ M 1) ¸ sd A 11 17 10 0.60 B 225 175 100 ­0.50 C 9 12 7 0.43 D 23 31 12 0.75 ES : effect size (GLM) ave = 0.32
Interpretation of ES • ES = 0.43 implies (for 2 groups) treatment mean is 0.43 SD units above control mean • from normal table, 0.43 SD = 67%tile • i.e., an average person in treatment group is better than 67% people in control group
Types of “ Effect Size Effect Size ” ” ES (specific) : standardized difference ES (Generic) : • correlation coefficient • odds ratio / relative risk • difference in proportion Different “types” in the same meta­analysis ?
Steps in Meta ­ ­Analysis Analysis • Get results of each study into common metric – effect size (continuous data) – correlation coefficient (continuous) – odds ratio, relative risk (categorical) • Combine results to form summary statistics • Test overall significance • Compare whether individual results are homogeneous (software demo)
Using SPSS (odds ratio) Study 1 I C ­­­­­­­­­­­­­­­­­­­­­­­­­­­­ Outcome Yes 10 20 No 30 40 ­­­­­­­­­­­­­­­­­­­­­­­­­­­­ Total 100 100 Study 2 I C ­­­­­­­­­­­­­­­­­­­­­­­­­­­­ Outcome Yes 25 44 No 175 156 ­­­­­­­­­­­­­­­­­­­­­­­­­­­­ Total 200 200
Using SPSS (data set ­ ­up) up) Study ­­­­­ 1 1 1 1 2 2 2 2 Row ­­­ 1 1 2 2 1 1 2 2 Col ­­­ 1 2 1 2 1 2 1 2 Data ­­­­ 10 20 30 40 25 44 175 156
Output ­­­­­­­­­­­­­­­ * Breslow­Day test of homogeneity * Mantel­Haenszel common odds ratio Question !! Study ­­­­­ X ­­ Y ­­ 1 .. .. 1 .. .. 1 .. .. 1 .. .. 2 .. .. 2 .. .. 2 2 .. .. .. ..
How to get common correlation coefficient using SPSS when raw data available ? 160 140 120 100
80
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Y 40
20
20 X 40 60 80 100 120 140 Partial correlation a Coefficients Unstandardized Standardized Coefficients Coefficients Model B Std. Error Beta t 1 (Constant) 44.447 16.714 2.659 X .824 .135 .742 6.097 S ­26.013 12.313 ­.257 ­2.113 a.Dependent Variable: Y Correlations Sig. Zero­order Partial Part .017 .000 .997 .828 .100 .050 ­.993 ­.456 ­.035 Fixed vs Random Effects Models • Fixed, which assumes all studies – no heterogeneity (can be tested using Cochran test) (confidence interval artificially narrower if not) – estimating a single true underlying effect size • Random – assumes different underlying effect sizes – more conservative (because 2 variations)
Difficulties • Rounded p­value – e.g., p<0.05; NS; “**”, … • Calculating effect size (ES) from graph • ES calculated using different methods – E.g., t in 2 studies; chi­sq in 4 studies • Precise sample size not available – e.g. missing not reported for each variable
Limitations of Meta
Limitations of Meta ­­ Analysis • Published research biased in favour of significant findings => biased meta­analysis results • Difficult to have research with exactly the same measuring techniques, definitions of variables, …
Publication Bias – Funnel Plot 6 5 Inverse SE 4 3 2 1 0
­3 ­2 ­1 0 Log Odds Ratio 1 2 3 “ Classic Classic ” ” Publication Bias 6 5 Inverse SE 4 3 2 1 0
­3.0 ­2.0 ­1.0 0.0 Log OR 1.0 2.0 3.0 Publication Bias – ““ Adjustment
Adjustment ” • analyse only large studies • include unpublished studies – risky, quality of study questionable – Cook (1993) : 46/150 MA used unpublished results – 47% editors : OK to include – 30% : should not be included • prospective registration of trials • change in publication process
Sensitivity Analysis Impact of followings on Effect Size estimate • changing inclusion criteria • include and exclude unpublished studies • exclude small studies especially if publication bias suspected • quality : include only those judged “pass” by at least 2 raters
Study Quality • How to assess study quality ? • = = Critical appraisal ! • Quality Scoring System • Checklist • Workshop in Critical Appraisal • 20 ­ 24 January 2003 • Preview : next 4 slides
Problems ( Riet Riet et al, 1990) • chronic pain & acupuncture (effective ?) • could do meta­analysis : 51 papers • check methodology (next 3 slides) • maximum possible score : 100 • only 11 papers scored > 50 • highest score : 62 • poor quality (methodology) ! • meta­analysis, if done, result reliable ??
Methodological Criteria I • Comparability of Prognosis (35) – Homogeneity – Prestratification – Randomization – Compare relevant baseline variables shown – n >= 50 per group – loss to follow­up <= 20 3 3 12 2 10 5
Methodological Criteria II • Adequate Intervention (30) – avoidance of DNIC – adeq description of acupun procedures – quality of clinician(s) / therapist(s) – existing treatment in control group 2 10 15 3 • Data Presentation (5) – Readers can do inferential stat 5
Methodological Criteria III • Adequate Effect Measurement (30) – patients blinded – evaluator blinded – follow­up >= 3 months – pain as an outcome measure – use of medication – ADL – Remarks on side­effects 10 5 5 3 2 3 2
References Articles : • Gotzsche, Hammarquist & Burr; BMJ; 1998 • Schafer; Measu & Eval in Couns & Develop; 1999 • References from these 2 articles Books • Glass, McGaw & Smith; 1981 • Wolf; 1986 • Cook et al; 1994