title: Combining randomized and non-randomized evidence in clinical research: a review of methods and applications.
abstract: Researchers may have multiple motivations for combining disparate pieces of evidence in a meta-analysis, such as generalizing experimental results or increasing the power to detect an effect that a single study is not able to detect. However, while in meta-analysis, the main question may be simple, the structure of evidence available to answer it may be complex. As a consequence, combining disparate pieces of evidence becomes a challenge. In this review, we cover statistical methods that have been used for the evidence-synthesis of different study types with the same outcome and similar interventions. For the methodological review, a literature retrieval in the area of generalized evidence-synthesis was performed, and publications were identified, assessed, grouped and classified. Furthermore real applications of these methods in medicine were identified and described. For these approaches, 39 real clinical applications could be identified. A new classification of methods is provided, which takes into account: the inferential approach, the bias modeling, the hierarchical structure, and the use of graphical modeling. We conclude with a discussion of pros and cons of our approach and give some practical advice.
authors.affiliation: Coordination Center for Clinical Trials, University of Duesseldorf, Germany.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Verde
authors.affiliation: Coordination Center for Clinical Trials, University of Duesseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ohmann
mesh_terms: D001499:Bayes Theorem; D015982:Bias; D056808:Biostatistics / Q000379:methods*; D019317:Evidence-Based Medicine / Q000706:statistics & numerical data; D006801:Humans; D016013:Likelihood Functions; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012044:Regression Analysis
keywords: bias modeling; cross‐design synthesis; generalized evidence synthesis; hierarchical Bayesian models; network meta‐analysis; observational studies; randomized control trials