The role of MTM in Overviews of Reviews
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1 Deborah Caldwell The role of MTM in Overviews of Reviews Comparing Multiple Interventions Methods Group Keystone, 2010
2 Why we need overviews of reviews Explosion in RCTs necessitated systematic reviews. More recently an explosion in systematic reviews Over 3000 published reviews on Cochrane library Multiple reviews for same clinical condition 22 reviews of smoking cessation interventions (42 distinct ( meta-analyses regimes in 38 separate ( reviews Management of adult asthma (19 Management of primary hypertension (9 reviews, 10 protocols).
3 Aim of an overview of reviews Originally formulated to: Summarise results of multiple reviews into a single accessible document. Don t repeat/ update literature searches, eligibility assessment or evidence synthesis Extract summary effect estimates as reported in component reviews, reformatted in tables or figures Audience: decision makers/ clinicians Which treatment should I use for this condition?
4 Example: nocturnal enuresis* Treatment comparison RR 95% CI % change Alarm vs no treatment % Alarm vs DBT % Alarm vs Desmopressin % Alarm vs Imipramine % Alarm vs CBT % CBT vs no treatment % DBT vs no treatment % DBT + alarm vs no treatment % Diclofenac vs no treatment % Imipramine vs no treatment % OUTCOME: Failure to achieve 14 days consecutive dry nights *Russell & Kiddoo (2006) Evid-Based Child Health
5 Example: nocturnal enuresis* Treatment comparison RR 95% CI % change Alarm vs no treatment % Alarm vs DBT % Alarm vs Desmopressin % Alarm vs Imipramine % Alarm vs CBT % CBT vs no treatment % DBT vs no treatment % DBT + alarm vs no treatment % Diclofenac vs no treatment % Imipramine vs no treatment % OUTCOME: Failure to achieve 14 days consecutive dry nights
6 Example: nocturnal enuresis* Treatment comparison RR 95% CI % change Alarm vs no treatment % Alarm vs DBT % Alarm vs Desmopressin % Alarm vs Imipramine % Alarm vs CBT % CBT vs no treatment % DBT vs no treatment % DBT + alarm vs no treatment % Diclofenac vs no treatment % Imipramine vs no treatment % OUTCOME: Failure to achieve 14 days consecutive dry nights
7 Indirect comparisons In absence of direct evidence for treatments B vs C, an indirect estimate of log risk ratio lrr BC can be obtained from RCTs comparing A vs B and A vs C: A B C LRR BC = LRR AC LRR AB ( 2005 ) *Bucher HC, et al.(1997); Glenny et al 7
8 Example: nocturnal enuresis* Treatment comparison RR 95% CI % change Alarm vs no treatment % Alarm vs DBT % Alarm vs Desmopressin % Alarm vs Imipramine % Alarm vs CBT % CBT vs no treatment % DBT vs no treatment % DBT + alarm vs no treatment % Diclofenac vs no treatment % Imipramine vs no treatment % OUTCOME: Failure to achieve 14 days consecutive dry nights
9 Multiple treatment meta-analysis Simultaneous comparison of multiple treatments Internally consistent set of estimates of relative treatment effect Probability that each treatment is the most effective Key assumption: dˆ = dˆ -dˆ BC AC AB The estimated in the BC trials is the same as the dˆbc dˆ = dˆ -dˆ BC AC AB estimated in the AC and AB trials. Concern that assumption of consistency is not safe.
10 Network of evidence Cognitive Therapy Imipramine DBT Placebo Alarm Diclofenac DBT+ alarm Desmopressin
11 Fixed effect summaries Treatment comparison ( reported ) RR RR ( MTC ) Deviance Alarm vs no treatment Alarm vs DBT Alarm vs Desmopressin Alarm vs Imipramine Alarm vs CBT CBT vs no treatment 0.65 DBT vs no treatment DBT+alarm vs no treatment 1.00 Diclofenac vs no treatment 1.01 Imipramine vs no treatment
12 Fixed effect summaries Treatment comparison ( reported ) RR RR ( MTC ) Deviance Alarm vs no treatment Alarm vs DBT Alarm vs Desmopressin Alarm vs Imipramine Alarm vs CBT CBT vs no treatment 0.65 DBT vs no treatment DBT+alarm vs no treatment 1.00 Diclofenac vs no treatment 1.01 Imipramine vs no treatment Residual deviance: 25.8
13 Reconsider the evidence Inappropriate use of fixed effect summaries underestimating uncertainty? Statistically significant heterogeneity in 7/ 10 pairwise contrasts. Random effects pairwise meta-analyses for each comparison in Stata. Random effects pooled estimates used in aggregate level MTC.
14 Random effects pooled summaries Treatment comparison RR Expected RR Deviance Alarm vs control Alarm vs DBT Alarm vs Desmopressin Alarm vs Imipramine Alarm vs CBT CBT vs control DBT vs control DBT + alarm vs control Diclofenac vs control Imipramine vs control Residual deviance = 7.113
15 Probability treatment x is best : Random effects 14 day dry nights Probability best Nothing % Alarm % DBT % Desmopressin % Imipramine % CBT % DBT+alarm % Diclofenac %
16 Summary MTM the only way to generate coherent summaries of treatment effect in OoRs. I used a pooled summaries MTM here for teaching purposes only Trial-level MTM is preferable because: Pooled summaries are further level of aggregation: more ( fallacy susceptible to confounders? (ecological Summaries from component reviews subject to ( corrections approximations (e.g. continuity Multi-arm trials handled correctly More detail on this will be provided in the basic and advanced MTM sessions (on Thursday and Friday see programme book for more detail).
17 Comparing Multiple Interventions Methods Group Recently formed (registered on 27 th Sept!) to address the issues we have outlined in this workshop. The scope of the group will focus on methodology for comparing multiple interventions for a common condition, both in Cochrane Intervention reviews addressing multiple interventions and in Cochrane Overviews of reviews. We also aim to provide peer review and specialist advice to review teams and CRGs. Co-convenors are: Lorne Becker (USA), Deborah Caldwell (UK), Julian Higgins, (UK )Tianjing Li (USA), Georgia Salanti (Greece) and Chris Schmidt (USA).
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