Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically.
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ABSTRACT:
SUBMITTER: Sena ES
PROVIDER: S-EPMC4013765 | biostudies-other | 2014 May
REPOSITORIES: biostudies-other
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Project description:BackgroundResults of new studies should be interpreted in the context of what is already known to compare results and build the state of the science. This systematic review and meta-analysis aimed to identify and synthesise results from meta-research studies examining if original studies within health use systematic reviews to place their results in the context of earlier, similar studies.MethodsWe searched MEDLINE (OVID), EMBASE (OVID), and the Cochrane Methodology Register for meta-research studies reporting the use of systematic reviews to place results of original clinical studies in the context of existing studies. The primary outcome was the percentage of original studies included in the meta-research studies using systematic reviews or meta-analyses placing new results in the context of existing studies. Two reviewers independently performed screening and data extraction. Data were synthesised using narrative synthesis and a random-effects meta-analysis was performed to estimate the mean proportion of original studies placing their results in the context of earlier studies. The protocol was registered in Open Science Framework.ResultsWe included 15 meta-research studies, representing 1724 original studies. The mean percentage of original studies within these meta-research studies placing their results in the context of existing studies was 30.7% (95% CI [23.8%, 37.6%], I2=87.4%). Only one of the meta-research studies integrated results in a meta-analysis, while four integrated their results within a systematic review; the remaining cited or referred to a systematic review. The results of this systematic review are characterised by a high degree of heterogeneity and should be interpreted cautiously.ConclusionOur systematic review demonstrates a low rate of and great variability in using systematic reviews to place new results in the context of existing studies. On average, one third of the original studies contextualised their results. Improvement is still needed in researchers' use of prior research systematically and transparently-also known as the use of an evidence-based research approach, to contribute to the accumulation of new evidence on which future studies should be based.Systematic review registrationOpen Science registration number https://osf.io/8gkzu/.
| S-EPMC9446778 | biostudies-literature
Project description:Evidence-based decision making is a hallmark of effective veterinary clinical practice. Scoping reviews, systematic reviews, and meta-analyses all are methods intended to provide transparent and replicable ways of summarizing a body of research to address an important clinical or public health issue. As these methods increasingly are being used by researchers and read by practitioners, it is important to understand the distinction between these techniques and to understand what research questions they can, and cannot, address. This review provides an overview of scoping reviews, systematic reviews, and meta-analysis, including a discussion of the method and uses. A sample dataset and coding to conduct a simple meta-analysis in the statistical program R also are provided. Scoping reviews are a descriptive approach, designed to chart the literature around a particular topic. The approach involves an extensive literature search, following by a structured mapping, or charting, of the literature. The results of scoping reviews can help to inform future research by identifying gaps in the existing literature and also can be used to identify areas where there may be a sufficient depth of literature to warrant a systematic review. Systematic reviews are intended to address a specific question by identifying and summarizing all of the available research that has addressed the review question. Questions types that can be addressed by a systematic review include prevalence/incidence questions, and questions related to etiology, intervention efficacy, and diagnostic test accuracy. The systematic review process follows structured steps with multiple reviewers working in parallel to reduce the potential for bias. An extensive literature search is undertaken and, for each relevant study identified by the search, a formal extraction of data, including the effect size, and assessment of the risk of bias is performed. The results from multiple studies can be combined using meta-analysis. Meta-analysis provides a summary effect size, and allows heterogeneity of effect among studies to be quantified and explored. These evidence synthesis approaches can provide scientific input to evidence-based clinical decision-making for veterinarians and regulatory bodies, and also can be useful for identifying gaps in the literature to enhance the efficiency of future research in a topic area.
| S-EPMC6997489 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-02-03 | E-GEOD-20186 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-02-03 | GSE20186 | GEO
Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD). The substantia nigra samples from 8 PD subjects were obtained from the Human Brain and Spinal Fluid Resource Center, VAMC, Los Angeles, CA, the Mind Unit Brain Bank at the University of Rochester, Rochester, NY, and from Dr. E. Masliah at UCSD, San Diego, CA, and 9 control subjects were obtained from the University of Rochester Alzheimer's Disease Center brain bank. The RNA was extracted using Trizol reagent (Invitrogen), DNAse treated with Qiagen DNAse, and analyzed on a bioanalyzer. The complementary RNA was fragmented and hybridized to Affymetrix human U133A arrays. The total 17 Affymetrix .CEL files were normalized to "all probe sets" in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.
2011-01-20 | E-GEOD-20163 | biostudies-arrayexpress
Project description:Analysis of substantia nigra from postmortem brains of 4 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Fresh frozen tissue blocks from cerebellar hemispheres of PD patients and controls were provided by the Queens Square Brain Bank for Neurological Disorders (London, UK). Total RNA was isolated from about 500 mg fresh frozen postmortem tissue from each subject by using Trizol reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's protocol and further purified using the RNeasy mini kit (Qiagen, Hilden, Germany). Quality of the extracted total RNA was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies, Boblingen, Germany). Cerebellar mRNA with the following criteria: two distinct visible peaks for 18 s and 20 s RNA with lack of multiple small peaks indicating major degradation in Agilent Bioanalyzer fluorograms and GAPDH 3′/5′ ratios smaller 5.0 and percentage present calls greater 40% for the parameter assessed by chip hybridization were hybridized on Affymetrix human U133A GeneChip Array. Sample labeling, hybridization to arrays and image scanning (Affymetrix® GeneChip® Scanner 2500, Agilent technologies, Boblingen, Germany) were performed using standard Affymetrix® protocol (Affymetrix® Expression Analysis Technical Manual) as described previously (Bonin et al, Brain Res. Mol. Brain Res. 126, 2004). The Affymetrix .CEL files were normalized to “all probe sets” in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.
2011-01-20 | E-GEOD-20314 | biostudies-arrayexpress
Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Substantia nigra samples from 6 PD and 5 control subjects were obtained. At autopsy, brain hemispheres were frozen in liquid nitrogen and stored at -80C in the Kathleen Price Bryan Brain Bank in the Alzheimer's Disease Research Center at Duke University. Using the RNAgents kit (Promega, Madison, Wis), RNA was extracted from SN and adjacent midbrain tissues. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Twenty micrograms of biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133A microarrays. The Affymetrix .CEL files were normalized to "all probe sets" in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.
2011-01-20 | E-GEOD-20164 | biostudies-arrayexpress
Project description:In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common-along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE's] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015-2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews.
| S-EPMC8128274 | biostudies-literature
Project description:The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also a moral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic reviews. In particular, we illustrate how these reviews can help improve the methodological quality of animal experiments, make the choice of an animal model and the translation of animal data to the clinic more evidence-based, and implement the 3Rs. Moreover, we discuss which measures are being taken and which need to be taken in the future to ensure that systematic reviews will actually contribute to optimizing experimental design and thereby to meeting a necessary condition for making the use of animals in these experiments justified.
| S-EPMC4276599 | biostudies-literature
Project description:Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta-analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC-derived conditioned media (MSC-CM). Lung alveolarization was the primary outcome. We used random effects models for data analysis and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened 990 citations; 25 met inclusion criteria. All used hyperoxia-exposed neonatal rodents to model BPD. MSCs significantly improved alveolarization (Standardized mean difference of -1.330, 95% confidence interval [CI -1.724, -0.94, I2 69%]), irrespective of timing of treatment, source, dose, or route of administration. MSCs also significantly ameliorated pulmonary hypertension, lung inflammation, fibrosis, angiogenesis, and apoptosis. Similarly, MSC-CM significantly improved alveolarization, angiogenesis, and pulmonary artery remodeling. MSCs, tested exclusively in hyperoxic rodent models of BPD, show significant therapeutic benefit. Unclear risk of bias and incomplete reporting in the primary studies highlights nonadherence to reporting standards. Overall, safety and efficacy in other species/large animal models may provide useful information for guiding the design of clinical trials. Stem Cells Translational Medicine 2017;6:2079-2093.
| S-EPMC5702524 | biostudies-literature