Author Affiliations: Department of Pharmacology and Clinical Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Greece (akyrgidi@gmail.com).
To the Editor: The meta-analysis by Dr Ryan and colleagues examining the association between biologic therapies for chronic plaque psoriasis and cardiovascular events reported no significant difference in the rate of major adverse cardiovascular events in patients receiving biologic therapies vs placebo.1 The rosiglitazone example demonstrated that single trials can be underpowered to provide conclusive evidence regarding rare cardiovascular events and meta-analyses can improve power.2 For meta-analyses, availability of high-quality data on harms and selection of the most appropriate analytical methods are essential.2 Specific concerns are raised about the validity of the findings by Ryan et al.
The authors used Mantel-Haenszel fixed-effects methods with absolute risk differences as the effect measure.1 Bradburn et al,3 after evaluating performance of 12 methods for pooling rare events, found that many of the most commonly used meta-analytical methods were biased and suboptimal in performance and gave misleading results. They concluded that for event rates below 1%, the Peto 1-step odds ratio method was the least biased and most powerful method and that bias was greater when the Mantel-Haenszel odds ratio method was used.3 Fixed-effects models assume that included studies share a common true effect size. Because random-effects models assume that studies were drawn from populations that differ from each other in ways that could influence the treatment effect, they are more appropriate in meta-analyses of trials studying different treatments. Also meta-analytical methods that calculate risk differences tend to show conservative confidence interval coverage and low statistical power.3 Because neither Peto odds ratio nor random-effects Mantel-Haenszel methods, which would be the most appropriate statistical methods, were used, the results of the study by Ryan et al1 might be misleading.
The authors pointed out that high-quality data on harms were not available. Conduct of included studies with decreased vigilance for adverse cardiac events, failure to report serious adverse events in included studies, and the short duration of placebo-controlled phases may have further compromised results of the meta-analysis.
Since cardiovascular events are uncommon and long-term outcomes, a meta-analysis of observational studies following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines4 could be important in detecting underestimation or overestimation of the effect and identifying critical information for efficient design of future randomized controlled trials, such as high-risk subgroups.5
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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