Meta-Analyses of Animal Studies: An Introduction of a Valuable Instrument to Further Improve Healthcare

Hooijmans, Carlijn R.; IntHout, Joanna; Ritskes‐Hoitinga, Merel; Rovers, Maroeska M.

doi:10.1093/ilar/ilu042

Cited by 149 publications

(138 citation statements)

References 31 publications

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“…To account for anticipated heterogeneity, we pooled effect sizes using random-effects meta-analysis, which considers the within-study and between-study variability and weights each study accordingly. Heterogeneity was quantified using I2 and T2 statistics 29 , 31 . Studies with missing data on any of the pre-defined experimental variables were excluded from the meta-analysis.…”

Section: Methodsmentioning

confidence: 99%

Remote ischaemic conditioning reduces infarct size in animalin vivomodels of ischaemia-reperfusion injury: a systematic review and meta-analysis

et al. 2016

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AimsThe potential of remote ischaemic conditioning (RIC) to ameliorate myocardial ischaemia-reperfusion injury (IRI) remains controversial. We aimed to analyse the pre-clinical evidence base to ascertain the overall effect and variability of RIC in animal in vivo models of myocardial IRI. Furthermore, we aimed to investigate the impact of different study protocols on the protective utility of RIC in animal models and identify gaps in our understanding of this promising therapeutic strategy.Methods and resultsOur primary outcome measure was the difference in mean infarct size between RIC and control groups in in vivo models of myocardial IRI. A systematic review returned 31 reports, from which we made 22 controlled comparisons of remote ischaemic preconditioning (RIPreC) and 21 of remote ischaemic perconditioning and postconditioning (RIPerC/RIPostC) in a pooled random-effects meta-analysis. In total, our analysis includes data from 280 control animals and 373 animals subject to RIC. Overall, RIPreC reduced infarct size as a percentage of area at risk by 22.8% (95% CI 18.8–26.9%), when compared with untreated controls (P < 0.001). Similarly, RIPerC/RIPostC reduced infarct size by 22.2% (95% CI 17.1–25.3%; P < 0.001). Interestingly, we observed significant heterogeneity in effect size (T2 = 92.9% and I2 = 99.4%; P < 0.001) that could not be explained by any of the experimental variables analysed by meta-regression. However, few reports have systematically characterized RIC protocols, and few of the included in vivo studies satisfactorily met study quality requirements, particularly with respect to blinding and randomization.ConclusionsRIC significantly reduces infarct size in in vivo models of myocardial IRI. Heterogeneity between studies could not be explained by the experimental variables tested, but studies are limited in number and lack consistency in quality and study design. There is therefore a clear need for more well-performed in vivo studies with particular emphasis on detailed characterization of RIC protocols and investigating the potential impact of gender. Finally, more studies investigating the potential benefit of RIC in larger species are required before translation to humans.

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Section: Methodsmentioning

confidence: 99%

Remote ischaemic conditioning reduces infarct size in animalin vivomodels of ischaemia-reperfusion injury: a systematic review and meta-analysis

et al. 2016

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“…25 It has been evident that UC is more common in Asia and the United States than CD, but recent epidemiological studies have shown that the incidence of CD is rising up. 45 Thus, this study was intended to provide a systematic review and a metaanalysis of published original research articles that have assessed the effects of ALA and its derivative 'AL-1' on the IBD symptoms. 28 A number of argumentative F I G U R E 1 Chemical structures of A, alpha lipoic acid; B, andrographolide acid; and C, andrographolide-lipoic acid-1 factors, such as dysregulation of immune cascades and imbalanced cytokine networks, environment, genetics, and manipulation of normal flora are mostly suspected as IBD etiology.…”

Section: Introductionmentioning

confidence: 99%

Effects of alpha lipoic acid and its derivative “andrographolid‐lipoic acid‐1” on ulcerative colitis: A systematic review with meta‐analysis of animal studies

Moeinian

Abdolghaffari

Nikfar

et al. 2018

J of Cellular Biochemistry

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We aimed to review and meta‐analyze the inflammatory and oxidative factors following alpha lipoic acid (ALA) and its derivative “andrographolid‐lipoic acid‐1” (AL‐1) in ulcerative colitis (UC). ALA plays an important role in scavenging intracellular radicals and inflammatory elements. AL‐1 is found in herbal medicines with potent anti‐inflammatory properties. Data were collected from the Google Scholar, PubMed, Scopus, Evidence‐based medicine/clinical trials, and Cochrane library database until 2017, which finally resulted in 22 animal studies (70 rats and 162 mice). The beneficial effects of ALA or AL‐1 on the most important parameters of UC were reviewed; also, studies were considered separately in mice and rats. Administration of ALA and AL‐1 significantly reduced the tumor necrosis factor‐α level compared with the controls, while data were not noteworthy in the meta‐analysis (mean differences = −18.57 [95% CI = −42.65 to 5.51], P = 0.13). In spite of insignificant decrease in meta‐analysis outcomes (differences = 6.92 [95% CI = −39.33 to 53.16], P = 0.77), a significant reduction in myeloperoxidase activity was shown following ALA or AL‐1 treatment compared with the controls. Despite significant differences in each study, we had to exclude some studies to homogenize data for meta‐analyzing as they showed insignificant results. Interleukin 6, cyclooxygenase‐2, glutathione, malondialdehyde, superoxide dismutase, histopathological score, macroscopic and microscopic scores, disease activity index, body weight change, and colon length were also reviewed. Most studies have emphasized on significant positive effects of ALA and AL‐1. Comprehensive clinical trials are obligatory to determine the precious position of ALA or AL‐1 in the management of UC.

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“…Possibly, lessons can be learned from the experiences made when adapting and applying meta-analyses to pre-clinical animal studies (Vesterinen et al 2014, Hooijmans et al 2014b). Meta-analysis of human epidemiological studies has been applied to assess neurobehavioral effects of metal or organic solvent exposure in an occupational setting (e.g., Goodman et al 2002; Meyer-Baron 2005).…”

Section: Preamblementioning

confidence: 99%

A primer on systematic reviews in toxicology

Hoffmann

Vries²,

Stephens

et al. 2017

Arch Toxicol

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Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored. To provide the toxicology community with a starting point for conducting or understanding systematic reviews, we herein summarized available guidance documents from various fields of application. We have elaborated on the systematic review process by breaking it down into ten steps, starting with planning the project, framing the question, and writing and publishing the protocol, and concluding with interpretation and reporting. In addition, we have identified the specific methodological challenges of toxicological questions and have summarized how these can be addressed. Ultimately, this primer is intended to stimulate scientific discussions of the identified issues to fuel the development of toxicology-specific methodology and to encourage the application of systematic review methodology to toxicological issues.

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Meta-Analyses of Animal Studies: An Introduction of a Valuable Instrument to Further Improve Healthcare

Cited by 149 publications

References 31 publications

Remote ischaemic conditioning reduces infarct size in animalin vivomodels of ischaemia-reperfusion injury: a systematic review and meta-analysis

Remote ischaemic conditioning reduces infarct size in animalin vivomodels of ischaemia-reperfusion injury: a systematic review and meta-analysis

Effects of alpha lipoic acid and its derivative “andrographolid‐lipoic acid‐1” on ulcerative colitis: A systematic review with meta‐analysis of animal studies

A primer on systematic reviews in toxicology

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