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Since the early 1990s the number of systematic reviews (SR) of animal studies has steadily increased. There is, however, little guidance on when and how to conduct a meta-analysis of human-health-related animal studies. To gain insight about the methods that are currently used we created an overview of the key characteristics of published meta-analyses of animal studies, with a focus on the choice of effect size measures. An additional goal was to learn about the rationale behind the meta-analysis methods used by the review authors. We show that important details of the meta-analyses are not fully described, only a fraction of all human-health-related meta-analyses provided rationales for their decision to use specific effect size measures. In addition, our data may suggest that authors make post-hoc decisions to switch to another effect size measure during the course of their meta-analysis, and possibly search for significant effects. Based on analyses in this paper we recommend that review teams: 1) publish a review protocol before starting the conduct of a SR, prespecifying all methodological details (providing special attention to the planned meta-analysis including the effect size measure and the rational behind choosing a specific effect size, prespecifying subgroups and restricting the number of subgroup analyses), 2) always use the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist to report your SR of animal studies, and 3) use the random effects model (REM) in human-health-related meta-analysis of animal studies, unless the assumptions for using the fixed effect model (FEM) are all met.

The current report is the result of the recent EFSA‐EBTC initiative to advance the use of automation tools in systematic reviews. The working group members identified the need for data exchange standards to facilitate transferring data between SR automation tools without loss or changes in data as a first priority. Closely related objectives identified were the concurrent development of data guidance and data content standards, and a strategy for governance of the resulting data standards, including their maintenance and regular updates. These conversations led up to the organization of workshops to initiate the development of data standards, as described in the current report. The EFSA‐EBTC collaboration organized a four half‐day workshop for an extensive group of stakeholders actively involved in the development or use of SR automation tools. The main objectives were 1) to generate a common understanding of the needs and hurdles for data standards in SR automation, 2) to collate viewpoints from all relevant stakeholders on how such standards may be developed, and 3) to kick‐off the development process. Three preparatory workshops preceding the final workshop were organized to clarify the scope and objectives of the main workshop. This external scientific report contains the summary of the preparatory and main workshops, as well as the proposed strategy for the process of how these data standards could be developed. The recommended next steps for development focus on further refining the aims, analysis of the landscape, interoperability with existing standards, setting up the infrastructure (e.g., establishing a governance structure and working groups containing all essential stakeholders), and the process of actual data standard development, launching and monitoring adoption of the standards. [ABSTRACT FROM AUTHOR]

The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. We performed a systematic review and meta-analysis by searching Medline and Embase (until 28 March, 2023) for RUPP studies in murine. Primary outcomes included maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump length, fetal reabsorptions, or antiangiogenic factors. We aimed to identify influential factors by meta-regression analysis. We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD = 24.1 mmHg; [22.6; 25.7]; n = 148), proteinuria (SMD = 2.3; [0.9; 3.8]; n = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2]; n = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4]; n = 34), and lower fetal weight (MD = −0.4 g; [−0.47; −0.34]; n = 113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Because of underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) increases cardiovascular risk by cardiac remodeling and programming. This systematic review and meta-analysis across species examines the use of echocardiography in FGR offspring at different ages. PubMed and Embase.com were searched for animal and human studies reporting on echocardiographic parameters in placental insufficiency-induced FGR offspring. We included six animal and 49 human studies. Although unable to perform a meta-analysis of animal studies because of insufficient number of studies per individual outcome, all studies showed left ventricular dysfunction. Our meta-analyses of human studies revealed a reduced left ventricular mass, interventricular septum thickness, mitral annular peak velocity, and mitral lateral early diastolic velocity at neonatal age. No echocardiographic differences during childhood were observed, although the small age range and number of studies limited these analyses. Only two studies at adult age were performed. Meta-regression on other influential factors was not possible due to underreporting. The few studies on myocardial strain analysis showed small changes in global longitudinal strain in FGR offspring. The quality of the human studies was considered low and the risk of bias in animal studies was mostly unclear. Echocardiography may offer a noninvasive tool to detect early signs of cardiovascular predisposition following FGR. Clinical implementation yet faces multiple challenges including identification of the most optimal timing and the exact relation to long-term cardiovascular function in which echocardiography alone might be limited to reflect a child's vascular status. Future research should focus on myocardial strain analysis and the combination of other (non)imaging techniques for an improved risk estimation. [ABSTRACT FROM AUTHOR]

Objective: The Symposium on Animal Systematic Reviews held 24 May 2022, sought to bring organisations working on animal literature searching and systematic reviews together into the same virtual space for introductions and discussion. Background: Groups working on animal research synthesis are often siloed into preclinical, veterinary, and One Health settings. This symposium sought to define commonalities and differences in methodologies, resources, and philosophies and to discuss future needs. Methods: The 3-hour virtual symposium for veterinarians, researchers, and information specialists began with introductions by panelists from organisations involved in searching the literature for animal studies and conducting systematic reviews. This was followed by a panel discussion and question and answer period. Results: Panelists identified a need to ensure planning and accurate description of primary animal studies as a precursor to quality systematic reviews. They acknowledged and discussed differences in evidence synthesis expectations and tools based on the type of review, the types of studies available on the topic, and the focus on preclinical, veterinary, or One Health topics. Conclusion: The need to increase the speed and quality of evidence reviews, and to automate updates, requires investing in the development of both skilled teams and platforms. The symposium provided a chance to identify existing resources, define challenges, and note gaps unique to systematic reviews of animal studies. Application: This symposium acts as a baseline for ongoing discussions centred on improving the culture and pipeline for evidence syntheses of animal studies that inform decision-making. [ABSTRACT FROM AUTHOR]