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Updated: Mar 12, 2026

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Step-by-step guide and checklists for selecting and conducting an evidence synthesis study using a framework for
1Center for Integrated Biostatistics and Epidemiology, Department of Biomedical Informatics, Biostatistics and Medical Epidemiology, University of Missouri School of Medicine, Columbia, MO, United States of America.
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Findings from multiple studies are used to develop informed decisions for future research and clinical practices. Evidence synthesis methods, in general, are recommended for synthesizing findings from multiple studies. Among all evidence synthesis methods, a high-quality systematic review is required for answering a specific, focused research question from an abundance of literature. Although the choice of a systematic review among all other evidence syntheses depends on the formulated question related to estimation or hypothesis, and the availability of high-quality original studies, evidence syntheses not adhering to systematic review guidelines are also referred to as systematic reviews in the literature. Moreover, planning, designing, analyzing, and reporting a systematic review and meta-analysis requires multiple steps that are not included in the standard checklist documents, such as preferred reporting items for systematic review and meta-analysis (PRISMA) or meta-analysis of observational studies in epidemiology (MOOSE). It is also unclear to investigators how to properly select a type of evidence synthesis method and the steps involved in conducting a meta-analysis. Although multiple documents are available for selecting appropriate evidence synthesis methods, writing a protocol for a systematic review and meta-analysis, and conducting meta-analyses, there is no single report that consolidates all of these in a comprehensive framework. Given emerging challenges in the quality of published systematic reviews, this report aims to facilitate a framework for approaches and methods in evidence synthesis (FRAMES) to readers in (a) understanding types of evidence synthesis methods with specific focus to a systematic reviews and meta-analyses, (b) explaining the objectives of meta-analysis study, (c) describing the steps and resources in conducting a systematic review and meta-analysis, and (d) exemplifying the challenges and their potential solutions in a meta-analysis study. This report provides evidence-based biostatistics checklists for conducting a systematic review and meta-analysis, and writing steps for a systematic review study. I believe the adoption of this guidance document in research and training for the conduct and writing of an evidence synthesis study can have a far-reaching impact on producing high-quality evidence for research and clinical practices.
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