scholarly journals Systematic Reviews and Meta-Analysis of Preclinical Studies: Why Perform Them and How to Appraise Them Critically

2014 ◽  
Vol 34 (5) ◽  
pp. 737-742 ◽  
Author(s):  
Emily S Sena ◽  
Gillian L Currie ◽  
Sarah K McCann ◽  
Malcolm R Macleod ◽  
David W Howells

The use of systematic review and meta-analysis of preclinical studies has become more common, including those of studies describing the modeling of cerebrovascular diseases. Empirical evidence suggests that too many preclinical experiments lack methodological rigor, and this leads to inflated treatment effects. The aim of this review is to describe the concepts of systematic review and meta-analysis and consider how these tools may be used to provide empirical evidence to spur the field to improve the rigor of the conduct and reporting of preclinical research akin to their use in improving the conduct and reporting of randomized controlled trials in clinical research. As with other research domains, systematic reviews are subject to bias. Therefore, we have also suggested guidance for their conduct, reporting, and critical appraisal.

2015 ◽  
Vol 10 (2) ◽  
pp. 150
Author(s):  
Joanne L. Jordan

A Review of: Westphal, A., Kriston, L., Hölzel, L.P., Härter, M., & von Wolff, A. (2014). Efficiency and contribution of strategies for finding randomized controlled trials: a case study from a systematic review on therapeutic interventions of chronic depression. Journal of Public Health Research, 3(2), 177. doi: 10.4081/jphr.2014.177 Abstract Objective – To evaluate the efficiency and contribution of additional searching strategies for finding randomized controlled trials (RCTs) in a systematic review. Design – A methodological case study. Setting – Biomedical literature. Methods – A sensitive search (defined as “the ratio of the number of relevant reports identified to the total number of relevant reports in existence”) was conducted of electronic databases, Cochrane CENTRAL database, MEDLINE, EMBASE, PsycInfo, CINAHL, BIOSIS, and Web of Science databases (Science and Social Science Citation Indexes). The following additional searching strategies were conducted: hand-searching contents of relevant journals (Archives of General Psychiatry, Journal of Consulting and Clinical Psychology, and Journal of Affective Disorders), citation tracking (forwards tracking using Social Science and Science Citation Index and backwards tracking by looking through reference lists of included studies), screening reference lists of relevant systematic reviews, searching clinical trials registers (ClinicalTrials.gov and ICTRP registers), and contacting first authors of included studies to find any similar unpublished studies. The number of articles identified by each of these methods was recorded and screened for inclusion in the systematic review. The authors calculated what they labelled as the ‘efficiency’ of each searching strategy (the number of included studies identified by the search method as a proportion of the full text articles screened) and the ‘contribution’ of the search strategies (the ratio of included studies identified by that method to the final number of included studies in the systematic review). The methodological quality of each included study was assessed using the Cochrane Risk of Bias Tool, which is a critical appraisal checklist used to judge the study’s value in the systematic review. The meta-analysis in the systematic review was conducted with and without the studies identified by the additional searching strategies to assess their impact on the review’s findings. Main Results – In total 50 studies were identified, 42 from electronic database searches and 8 from additional search strategies. As illustrated by the results in Table 1, the most useful additional search strategy was screening reference lists of relevant systematic reviews. Journal hand-searching and contacting authors also contributed to the review. Of the eight studies identified by the additional search strategies none were judged to have a low risk of bias (four had high risk of bias and four were unclear). Of the 42 included studies from electronic searches only 11 were judged to have a low risk of bias, whereas 9 studies had a high risk of bias and 22 were unclear. Excluding the eight studies retrieved from additional search strategies in the systematic review meta-analysis did not influence the results on the effectiveness of the different interventions for chronic depression. These studies were found to be indexed correctly on the electronic databases, but were not identified in the initial search. Conclusion – Additional search strategies, especially screening reference lists of systematic reviews and hand-searching relevant journals, retrieved a substantial number of relevant studies for a systematic review of interventions for treating chronic depression. However, results of the review’s meta-analysis did not differ when these additional studies (rated as either high or unclear risk of bias) were not included and search methods were time consuming. It might be reasonable to rely on electronic searching strategies when resources for conducting a systematic review are limited or when doing a “rapid review.” The benefits and limitations of additional search strategies should be considered particularly when resources or time for conducting a systematic review are limited. If the electronic database search is sensitive and includes the Cochrane CENTRAL database additional search strategies may not be necessary, but these findings should be tested in other research areas.


2020 ◽  
Author(s):  
Ting Wan Tan ◽  
Han Ling Tan ◽  
Chih Ming Chang

BACKGROUND Urinary tract infection (UTI) is one of common illness in newborn and infants. An accurate urine sample to diagnosis of UTI is crucial to ensure appropriate treatment to avoid delayed and false-treatment. However, data to assess the effectiveness and safety of non-invasive stimulation technique of collecting urine in newborn and infants are yet to be critically evaluated. OBJECTIVE This protocol aimed to conduct a systematic review and meta-analysis to evaluate the evidences related to the effectiveness and safety of non-invasive stimulation technique of collecting urine in newborn and infants. METHODS This protocol follows guideline according to Preferred Reporting Items for Systematic reviews and Meta-Analysis Protocol and registered on the International Prospective Register of Systematic Reviews. Seven databases will be searched from their inception to March 2020: PubMed, EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and cumulative index to nursing and allied health literature database. RESULTS This Systemic review will include randomized controlled clinical trials (RCTs) including quasi-randomized controlled trials (quasi-RCTs), observational studies (prospective cohort or retrospective cohort studies). We will perform data extraction, study selection, assessment with risk of bias and data analysis. Primary outcomes measure success in obtaining a urine sample. Secondary outcome measures included gender, age group, weight analysis, contamination rate and adverse effects. Study methodological appraisal of the studies will be assessed by the Cochrane Risk of Bias Tools. For sufficient data are available, a meta-analysis will be conducted. I2 statistics will be used to assess heterogeneity and identify potential sources. CONCLUSIONS This systematic review wills no requirement for ethical approval, without human beings involvement. This systematic review will be published electronically in a peer-reviewed journal, and will give healthcare practitioners good practical guide and information for the evidences related to the effectiveness of non-invasive stimulation techniques to collect urine in newborn and infants, aims to improve clinical outcomes.


2019 ◽  
Vol 3 (1) ◽  
pp. e000043 ◽  
Author(s):  
A B Ramos-Hryb ◽  
Z Bahor ◽  
S McCann ◽  
E Sena ◽  
M R MacLeod ◽  
...  

ObjectiveForced swimming test (FST) in rodents is a widely used behavioural test for screening antidepressants in preclinical research. Translational value of preclinical studies may be improved by appraisal of the quality of experimental design and risk of biases, which remains to be addressed for FST. The present protocol of a systematic review with meta-analysis aims to investigate the quality of preclinical studies employing FST to identify risks of bias in future publications. In addition, this protocol will help to determine the effect sizes (ES) for primary and secondary outcomes according to several aspects of the FST study design.Search strategy, Screening annotation, Data managementPublications reporting studies testing different classes of antidepressants in FST will be collected from Medline, SCOPUS and Web of Science databases. A broad list of inclusion criteria will be applied excluding those studies whereby FST is used as a stressor or studies reporting data from co-treatments. For assessing the quality of the included publications, the quality checklist adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by using the χ2statistic with n−1 degrees of freedom. Subgroup meta-analysis (meta-regression, and if necessary, stratified regression) will be performed when possible according to characteristics of study design and study quality to assess their impact on efficacy of the treatments. In addition, funnel plotting, Egger regression, and ‘trim and fill’ will be used to assess the risk of publication bias. Results of this protocol will help to create rational methodological guidelines for application of FST in rodents and improve the quality and translational value of preclinical research on antidepressant discovery.ReportingA preliminary version of the present protocol has been preregistered with Systematic Review Facility (http://syrf.org.uk/). A preprint version of the current protocol has been registered with Open Science Framework (https://osf.io/9kxm4/). Results will be communicated in scientific meetings and peer-reviewed journals. We plan to conduct an anonymous and online survey within the scientific community to ask researchers about their perception of risk of bias and their experience with the publication of negative results.


2017 ◽  
Vol 41 (5) ◽  
pp. 317-326 ◽  
Author(s):  
Neeti Mittal ◽  
Manoj Goyal ◽  
Parteek K Mittal

Systematic reviews and meta-analysis seek to answer a pre-framed research question to lead to a valid answer through a systematic, explicit and reproducible method of locating; identifying, including and appraising appropriate trials. The results are synthesized considering the methodological rigor of included trials. While the meta-analysis quantitatively pools the results from individual included studies, the systematic review summarizes the findings as qualitative conclusions. These reviews are crux of evidence based dentistry for various stake-holders, i.e., clinicians, researchers and policy-makers. Although the meticulous methodology of systematic review and meta-analysis minimizes the elements of bias, yet the validity and reliability of their findings should be explored prior to translating their conclusions to practice. The goal of this paper is to familiarize readers with rationale, conduct and appraisal of systematic review and meta-analysis. Further, guidance is provided on tracing potential elements of bias in the review to enable readers to judge the quality of evidence generated from the review.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sun Jo Kim ◽  
Cheol Woon Jung ◽  
Nguyen Hoang Anh ◽  
Suk Won Kim ◽  
Seongoh Park ◽  
...  

Background: Oat and its compounds have been found to have anti-inflammatory effects. Through this systematic review and meta-analysis, we aimed to determine an evidence-based link between oat consumption and inflammatory markers.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. By the end of April 2021, we included randomized controlled trials (RCTs) that investigated the anti-inflammatory effect of oat and oat-related products through screening PubMed, Embase, Web of Science, ClinicalTrial.gov, and CENTRAL. Meta-analysis was conducted with a random-effect model on the standardized mean difference (SMD) of the change scores of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Subgroup analyses were conducted to stratify confounding variables. The risk of bias was evaluated using the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to report the quality of evidence. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021245844).Results: Systematic screening of five databases yielded 4,119 studies, of which 23 RCTs were finally selected. For the four systemic inflammatory markers analyzed, no significant alterations were found after oat consumption. However, oat intake was found to significantly decrease CRP levels in subjects with one or more health complications (SMD: −0.18; 95% CI: −0.36, 0.00; P = 0.05; I2 = 10%). Furthermore, IL-6 levels were significantly decreased in subjects with dyslipidemia (SMD = −0.34; 95% CI: −0.59, −0.10; P = 0.006; I2 = 0%). These beneficial effects might be attributed to the effects of avenanthramide and β-glucan.Conclusions: Overall evidence supporting the alleviation of inflammatory response by oat intake was poor, calling for future studies including a larger sample size to confirm the findings.


2018 ◽  
Author(s):  
Joao Ricardo Nickenig Vissoci

BackgroundHarmful alcohol use leads to a large burden of disease and disability which disportionately impacts LMICs. The World Health Organization and the Lancet have issued calls for this burden to be addressed, but issues remain, primarily due to gaps in information. While a variety of interventions have been shown to be effective at reducing alcohol use in HICs, their efficacy in LMICs have yet to be assessed. This systematic review describes the current published literature on alcohol interventions in LMICs and conducts a meta analysis of clinical trials evaluating interventions to reduce alcohol use and harms in LMICs.MethodsIn accordance with PRISMA guidelines we searched the electronic databases Pubmed, EMBASE, Scopus,Web of Science, Cochrane, and Psych Info. Articles were eligible if they evaluated an intervention targeting alcohol-related harm in LMICs. After a reference and citation analysis, we conducted a quality assessment per PRISMA protocol. A meta-analysis was performed on the 39 randomized controlled trials that evaluated an alcohol-related outcome.ResultsOf the 3,801 articles from the literature search, 87 articles from 25 LMICs fit the eligibility and inclusion criteria. Of these studies, 39 randomized controlled trials were included in the meta-analysis. Nine of these studies focused specifically on medication, while the others focused on brief motivational intervention, brain stimulation, AUDIT-based brief interventions, WHO ASSIST-based interventions, group based education, basic screening and interventions, brief psychological or counseling, dyadic relapse prevention, group counseling, CBT, motivational + PTSD based interview, and health promotion/awareness. Conclusion Issues in determining feasible options specific to LMICs arise from unstandardized interventions, unequal geographic distribution of intervention implementation, and uncertain effectiveness over time. Current research shows that brain stimulation, psychotherapy, and brief motivational interviews have the potential to be effective in LMIC settings, but further feasibility testing and efforts to standardize results are necessary to accurately assess their effectiveness.


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