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Article Alert

The free Article Alert service delivers a weekly email to your inbox containing the most recently published articles on all aspects of systematic review and comparative effectiveness review methodologies.

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The Article Alert for the week of September 15, 2014 (sample articles)

Schild AHE, Voracek M. Finding your way out of the forest without a trail of bread crumbs: development and evaluation of two novel displays of forest plots. Res.Synth.Method. Epub 2014 Aug 14

Research has shown that forest plots are a gold standard in the visualization of meta-analytic results. However, research on the general interpretation of forest plots and the role of researchers' meta-analysis experience and field of study is still unavailable. Additionally, the traditional display of effect sizes, confidence intervals, and weights have repeatedly been criticized. The current work presents an online statistical cognition experiment in which a total of 279 researchers with experience in meta-analysis from 36 countries evaluated conventional forest plots and two novel versions of forest plots, namely, thick forest plots and rainforest plots. The results indicate certain biases in the interpretation of forest plots, especially with regard to heterogeneity, the distribution of weights, and the theoretical concept of confidence intervals. Although the two novel displays (thick forest plots and rainforest plots) are associated with slightly longer viewing times, they are at least as well-suited and esthetically and perceptively pleasing as the conventional displays while facilitating the correct and exhaustive interpretation of the meta-analytic information. Furthermore, it is advisable to combine conventional forest plots with distribution information of the individual effects, make confidence lines more visually striking, and to display a background grid in the graph.


Crowther MJ, Look MP, Riley RD. Multilevel mixed effects parametric survival models using adaptive Gauss-Hermite quadrature with application to recurrent events and individual participant data meta-analysis. Stat.Med. 2014 Sep 28;33(22):3844-58. PMID: 24789760.

Multilevel mixed effects survival models are used in the analysis of clustered survival data, such as repeated events, multicenter clinical trials, and individual participant data (IPD) meta-analyses, to investigate heterogeneity in baseline risk and covariate effects. In this paper, we extend parametric frailty models including the exponential, Weibull and Gompertz proportional hazards (PH) models and the log logistic, log normal, and generalized gamma accelerated failure time models to allow any number of normally distributed random effects. Furthermore, we extend the flexible parametric survival model of Royston and Parmar, modeled on the log-cumulative hazard scale using restricted cubic splines, to include random effects while also allowing for non-PH (time-dependent effects). Maximum likelihood is used to estimate the models utilizing adaptive or nonadaptive Gauss-Hermite quadrature. The methods are evaluated through simulation studies representing clinically plausible scenarios of a multicenter trial and IPD meta-analysis, showing good performance of the estimation method. The flexible parametric mixed effects model is illustrated using a dataset of patients with kidney disease and repeated times to infection and an IPD meta-analysis of prognostic factor studies in patients with breast cancer. User-friendly Stata software is provided to implement the methods.


Johnston BC, Patrick DL, Thorlund K, Busse JW, da Costa BR, Schünemann HJ, Guyatt GH. Patient-reported outcomes in meta-analyses-part 2: methods for improving interpretability for decision-makers. Health.Qual.Life.Outcomes. 2013 Dec 21;11:211. PMID: 24359184.

Systematic reviews and meta-analyses of randomized trials that include patient-reported outcomes (PROs) often provide crucial information for patients, clinicians and policy-makers facing challenging health care decisions. Based on emerging methods, guidance on improving the interpretability of meta-analysis of patient-reported outcomes, typically continuous in nature, is likely to enhance decision-making. The objective of this paper is to summarize approaches to enhancing the interpretability of pooled estimates of PROs in meta-analyses. When differences in PROs between groups are statistically significant, decision-makers must be able to interpret the magnitude of effect. This is challenging when, as is often the case, clinical trial investigators use different measurement instruments for the same construct within and between individual randomized trials. For such cases, in addition to pooling results as a standardized mean difference, we recommend that systematic review authors use other methods to present results such as relative (relative risk, odds ratio) or absolute (risk difference) dichotomized treatment effects, complemented by presentation in either: natural units (e.g. overall depression reduced by 2.4 points when measured on a 50-point Hamilton Rating Scale for Depression); minimal important difference units (e.g. where 1.0 unit represents the smallest difference in depression that patients, on average, perceive as important the depression score was 0.38 (95% CI 0.30 to 0.47) units less than the control group); or a ratio of means (e.g. where the mean in the treatment group is divided by the mean in the control group, the ratio of means is 1.27, representing a 27% relative reduction in the mean depression score).