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Researchers are increasingly turning to machine learning (ML) algorithms to investigate causal heterogeneity in randomized experiments. Despite their promise, ML algorithms may fail to accurately ascertain heterogeneous treatment effects…

Methodology · Statistics 2024-04-23 Kosuke Imai , Michael Lingzhi Li

Evidence syntheses and meta-analyses are used to inform clinical practice guidelines and health economic evaluations. However, heterogeneity of treatment effects poses a significant challenge. Conventional meta-analysis addresses…

Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…

Methodology · Statistics 2022-10-21 Liwen Wu , Qing Li , Mengya Liu , Jianchang Lin

Random-effects models are central to meta-analysis, yet the between-study variance is often underestimated when the number of studies is small. In such settings, confidence intervals become unduly narrow and fail to attain the nominal…

Methodology · Statistics 2025-11-18 Keisuke Hanada , Tomoyuki Sugimoto

Random effects meta-analysis is widely used for synthesizing studies under the assumption that underlying effects come from a normal distribution. However, under certain conditions the use of alternative distributions might be more…

[See paper for full abstract] Meta-analysis is a crucial tool for answering scientific questions. It is usually conducted on a relatively small amount of ``trusted'' data -- ideally from randomized, controlled trials -- which allow causal…

Machine Learning · Statistics 2024-07-15 Shiva Kaul , Geoffrey J. Gordon

The era of big data is coming, and evidence-based medicine is attracting increasing attention to improve decision making in medical practice via integrating evidence from well designed and conducted clinical research. Meta-analysis is a…

Methodology · Statistics 2016-10-05 Dehui Luo , Xiang Wan , Jiming Liu , Tiejun Tong

Identifying subgroups, which respond differently to a treatment, both in terms of efficacy and safety, is an important part of drug development. A well-known challenge in exploratory subgroup analyses is the small sample size in the…

Computation · Statistics 2016-06-28 Marius Thomas , Björn Bornkamp

The commonly used two-way fixed effects estimator is biased under correlated heterogeneity and can lead to misleading inference. The mean group estimator proposed by Pesaran and Smith (1995) is robust to correlated heterogeneity but…

Econometrics · Economics 2026-04-01 M. Hashem Pesaran , Liying Yang

Multivariate meta-analysis can be adapted to a wide range of situations for multiple outcomes and multiple treatment groups when combining studies together. The within-study correlation between effect sizes is often assumed known in…

Methodology · Statistics 2020-03-12 Xiaohuan Xue

Commonly, clinical trials report effects not only for the full study population but also for patient subgroups. Meta-analyses of subgroup-specific effects and treatment-by-subgroup interactions may be inconsistent, especially when trials…

Methodology · Statistics 2025-12-23 Renato Panaro , Christian Röver , Tim Friede

When direct measurement of a clinically relevant primary endpoint in a clinical trial is infeasible, a surrogate endpoint may be used instead to infer treatment effects. Trial-level surrogates predict the average treatment effect on the…

Methodology · Statistics 2026-05-06 Arthur Hughes , Rodolphe Thiébaut , Layla Parast , Boris P. Hejblum

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…

Methodology · Statistics 2018-09-11 Tim Friede , Christian Röver , Simon Wandel , Beat Neuenschwander

Randomization tests are a popular method for testing causal effects in clinical trials with finite-sample validity. In the presence of heterogeneous treatment effects, it is often of interest to select a subgroup that benefits from the…

Methodology · Statistics 2025-04-29 Zijun Gao

When there is interference, a subject's outcome depends on the treatment of others and treatment effects may take on several different forms. This situation arises often, particularly in vaccine evaluation. In settings where interference is…

Statistics Theory · Mathematics 2020-01-10 Erin E Gabriel

We study a panel data model with general heterogeneous effects where slopes are allowed to vary across both individuals and over time. The key dimension reduction assumption we employ is that the heterogeneous slopes can be expressed as…

Statistics Theory · Mathematics 2019-09-05 Victor Chernozhukov , Christian Hansen , Yuan Liao , Yinchu Zhu

According to Davey et al. (2011) with a total of 22,453 meta-analyses from the January 2008 Issue of the Cochrane Database of Systematic Reviews, the median number of studies included in each meta-analysis is only three. In other words,…

Methodology · Statistics 2020-02-12 Enxuan Lin , Tiejun Tong , Yong Chen , Yuedong Wang

Meta-analysis is an important statistical technique for synthesizing the results of multiple studies regarding the same or closely related research question. So-called meta-regression extends meta-analysis models by accounting for…

Methodology · Statistics 2023-02-22 Thilo Welz , Eric S. Knop , Tim Friede , Markus Pauly

BACKGROUND: Random-effects meta-analysis within a hierarchical normal modeling framework is commonly implemented in a wide range of evidence synthesis applications. More general problems may even be tackled when considering meta-regression…

Computation · Statistics 2022-12-27 Christian Röver , Tim Friede

With the evolution of single-cell RNA sequencing techniques into a standard approach in genomics, it has become possible to conduct cohort-level causal inferences based on single-cell-level measurements. However, the individual gene…

Methodology · Statistics 2025-04-23 Jin-Hong Du , Zhenghao Zeng , Edward H. Kennedy , Larry Wasserman , Kathryn Roeder