Case-mix heterogeneity across studies complicates meta-analyses. As a result of this, treatments that are equally effective on patient subgroups may appear to have different effectiveness on patient populations with different case mix. It is therefore important that meta-analyses be explicit for what patient population they describe the treatment effect. To achieve this, we develop a new approach for meta-analysis of randomized clinical trials, which use individual patient data (IPD) from all trials to infer the treatment effect for the patient population in a given trial, based on direct standardization using either outcome regression (OCR) or inverse probability weighting (IPW). Accompanying random-effect meta-analysis models are developed. The new approach enables disentangling heterogeneity due to case mix from that due to beyond case-mix reasons.
Model-based recursive partitioning (MOB) can be used to identify subgroups with differing treatment effects. The detection rate of treatment-by-covariate interactions and the accuracy of identified subgroups using MOB depend strongly on the sample size. Using data from multiple randomized controlled clinical trials can overcome the problem of too small samples. However, naively pooling data from multiple trials may result in the identification of spurious subgroups as differences in study design, subject selection and other sources of between-trial heterogeneity are ignored. In order to accoun…
Recent work has made important contributions in the development of causally-interpretable meta-analysis. These methods transport treatment effects estimated in a collection of randomized trials to a target population of interest. Ideally, estimates targeted toward a specific population are more interpretable and relevant to policy-makers and clinicians. However, between-study heterogeneity not arising from differences in the distribution of treatment effect modifiers can raise difficulties in synthesizing estimates across trials. The existence of such heterogeneity, including variations in tre…
Meta-analyses in orphan diseases and small populations generally face particular problems including small numbers of studies, small study sizes, and heterogeneity of results. However, the heterogeneity is difficult to estimate if only very few studies are included. Motivated by a systematic review in immunosuppression following liver transplantation in children we investigate the properties of a range of commonly used frequentist and Bayesian procedures in extensive simulation studies. Furthermore, the consequences for interval estimation of the common treatment effect in random effects meta-a…
This paper studies treatment effect models in which individuals are classified into unobserved groups based on heterogeneous treatment rules. Using a finite mixture approach, we propose a marginal treatment effect (MTE) framework in which the treatment choice and outcome equations can be heterogeneous across groups. Under the availability of instrumental variables specific to each group, we show that the MTE for each group can be separately identified. Based on our identification result, we propose a two-step semiparametric procedure for estimating the group-wise MTE. We illustrate the usefuln…
Meta-analysis combines pertinent information from existing studies to provide an overall estimate of population parameters/effect sizes, as well as to quantify and explain the differences between studies. However, testing the between-study heterogeneity is one of the most troublesome topics in meta-analysis research. Additionally, no methods have been proposed to test whether the size of the heterogeneity is larger than a specific level. The existing methods, such as the Q test and likelihood ratio (LR) tests, are criticized for their failure to control the Type I error rate and/or failure to …
Objective: We investigated the associations between risk of bias judgments from Cochrane reviews for sequence generation, allocation concealment and blinding and between-trial heterogeneity. Study Design and Setting: Bayesian hierarchical models were fitted to binary data from 117 meta-analyses, to estimate the ratio λ by which heterogeneity changes for trials at high/unclear risk of bias, compared to trials at low risk of bias. We estimated the proportion of between-trial heterogeneity in each meta-analysis that could be explained by the bias associated with specific design characteristics. R…
Successful modeling of degradation performance data is essential for accurate reliability assessment and failure predictions of highly reliable product units. The degradation performance measurements over time are highly heterogeneous. Such heterogeneity can be partially attributed to external factors, such as accelerated/environmental conditions, and can also be attributed to internal factors, such as material microstructure characteristics of product units. The latent heterogeneity due to the unobserved/unknown factors shared within each product unit may also exists and need to be considered…
Detection heterogeneity is inherent to ecological data, arising from factors such as varied terrain or weather conditions, inconsistent sampling effort, or heterogeneity of individuals themselves. Incorporating additional covariates into a statistical model is one approach for addressing heterogeneity, but is no guarantee that any set of measurable covariates will adequately address the heterogeneity, and the presence of unmodelled heterogeneity has been shown to produce biases in the resulting inferences. Other approaches for addressing heterogeneity include the use of random effects, or fini…
Covariate Informed Identification of Heterogeneity and Outliers in Longitudinal Data
University of Louisville（路易斯维尔大学）；Case Western Reserve University（凯斯西储大学）；Mass General Brigham, Harvard Medical School（麻省总医院布里格姆医院，哈佛医学院）；University of Missouri（密苏里大学）
The funnel plot is a graphical visualisation of summary data estimates from a meta-analysis, and is a useful tool for detecting departures from the standard modelling assumptions. Although perhaps not widely appreciated, a simple extension of the funnel plot can help to facilitate an intuitive interpretation of the mathematics underlying a meta-analysis at a more fundamental level, by equating it to determining the centre of mass of a physical system. We used this analogy, with some success, to explain the concepts of weighing evidence and of biased evidence to a young audience at the Cambridg…
Genetic association analyses often involve data from multiple potentially-heterogeneous subgroups. The expected amount of heterogeneity can vary from modest (e.g., a typical meta-analysis) to large (e.g., a strong gene--environment interaction). However, existing statistical tools are limited in their ability to address such heterogeneity. Indeed, most genetic association meta-analyses use a "fixed effects" analysis, which assumes no heterogeneity. Here we develop and apply Bayesian association methods to address this problem. These methods are easy to apply (in the simplest case, requiring on…
Longitudinal data tracking repeated measurements on individuals are highly valued for research because they offer controls for unmeasured individual heterogeneity that might otherwise bias results. Random effects or mixed models approaches, which treat individual heterogeneity as part of the model error term and use generalized least squares to estimate model parameters, are often criticized because correlation between unobserved individual effects and other model variables can lead to biased and inconsistent parameter estimates. Starting with an examination of the relationship between random …
Rich meta-epidemiological data sets have been collected to explore associations between intervention effect estimates and study-level characteristics. Welton et al. proposed models for the analysis of meta-epidemiological data, but these models are restrictive because they force heterogeneity among studies with a particular characteristic to be at least as large as that among studies without the characteristic. In this paper we present alternative models that are invariant to the labels defining the two categories of studies. To exemplify the methods, we use a collection of meta-analyses in wh…
