Quality and validity of large animal experiments in stroke: A systematic review.
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ABSTRACT:
SUBMITTER: Kringe L
PROVIDER: S-EPMC7585919 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Translation from preclinical animal research to clinical bedside has proven to be difficult to impossible in many fields of research (e.g. acute stroke, ALS and HIV vaccination development) with oncology showing particularly low translation rates (5% vs. 20% for cardiovascular diseases). Several investigations on published preclinical animal research have revealed that apart from plain species differences, translational problems can arise from low study quality (e.g. study design) or non-representative experimental conditions (e.g. treatment schedule). This review assessed the published experimental circumstances and quality of anti-angiogenic cancer drug development in 232 in vivo studies. The quality of study design was often insufficient; at least the information published about the experiments was not satisfactory in most cases. There was no quality improvement over time, with the exception of conflict of interest statements. This increase presumably arose mainly because journal guidelines request such statements more often recently. Visual inspection of data and a cluster analysis confirmed a trend described in literature that low study quality tends to overestimate study outcome. It was also found that experimental outcome was more favorable when a potential drug was investigated as the main focus of a study, compared to drugs that were used as comparison interventions. We assume that this effect arises from the frequent neglect of blinding investigators towards treatment arms and refer to it as hypothesis bias. In conclusion, the reporting and presumably also the experimental performance of animal studies in drug development for oncology suffer from similar shortcomings as other fields of research (such as stroke or ALS). We consider it necessary to enforce experimental quality and reporting that corresponds to the level of clinical studies. It seems that only clear journal guidelines or guidelines from licensing authorities, where failure to fulfill prevents publication or experimental license, can help to improve this situation.
| S-EPMC4589433 | biostudies-literature
Project description:BackgroundThe development of atrioventricular bioprosthesis has witnessed an increasing drive toward clinical translation over the last few decades. A significant challenge in the clinical translation of an atrioventricular bioprosthesis from bench to bedside is the appropriate choice of a large animal model to test the safety and effectiveness of the device.MethodsWe conducted a systematic review of pre-clinical in vivo studies that would enable us to synthesize a recommended framework. PRISMA (Preferred Reporting Items for Systematic Reviews and MetaAnalyses) guidelines were followed to identify and extract relevant articles.ResultsSheep was the most common choice of animal, with nine out of the 12 included studies being conducted on sheep. There were acute and chronic studies based on our search criteria. An average of ~20 and 5 animals were used for chronic and acute studies. One out of three acute studies and eight out of nine chronic studies were on stented heart valve bioprosthesis. All analyses were conducted on the implantation of atrioventricular valves with trileaflet, except for one chronic study on unileaflet valves and one chronic and acute study on bileaflet valves.ConclusionUnderstanding the variance in past pre-clinical study designs may increase the appropriate utilization of large animal models. This synthesized evidence provides a pre-clinical in vivo studies framework for future research on an atrioventricular bioprosthesis.
| S-EPMC10201874 | biostudies-literature
Project description:BackgroundThe vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address.Methods and findingsWe searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria--most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation.ConclusionsBy identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice. Please see later in the article for the Editors' Summary.
| S-EPMC3720257 | biostudies-literature
Project description:ObjectiveTo examine concordance between treatment effects in animal experiments and clinical trials. Study design Systematic review.Data sourcesMedline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS.Study selectionAnimal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head injury, antifibrinolytics in haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic stroke, antenatal corticosteroids to prevent neonatal respiratory distress syndrome, and bisphosphonates to treat osteoporosis. Review methods Data were extracted on study design, allocation concealment, number of randomised animals, type of model, intervention, and outcome.ResultsCorticosteroids did not show any benefit in clinical trials of treatment for head injury but did show a benefit in animal models (pooled odds ratio for adverse functional outcome 0.58, 95% confidence interval 0.41 to 0.83). Antifibrinolytics reduced bleeding in clinical trials but the data were inconclusive in animal models. Thrombolysis improved outcome in patients with ischaemic stroke. In animal models, tissue plasminogen activator reduced infarct volume by 24% (95% confidence interval 20% to 28%) and improved neurobehavioural scores by 23% (17% to 29%). Tirilazad was associated with a worse outcome in patients with ischaemic stroke. In animal models, tirilazad reduced infarct volume by 29% (21% to 37%) and improved neurobehavioural scores by 48% (29% to 67%). Antenatal corticosteroids reduced respiratory distress and mortality in neonates whereas in animal models respiratory distress was reduced but the effect on mortality was inconclusive (odds ratio 4.2, 95% confidence interval 0.85 to 20.9). Bisphosphonates increased bone mineral density in patients with osteoporosis. In animal models the bisphosphonate alendronate increased bone mineral density compared with placebo by 11.0% (95% confidence interval 9.2% to 12.9%) in the combined results for the hip region. The corresponding treatment effect in the lumbar spine was 8.5% (5.8% to 11.2%) and in the combined results for the forearms (baboons only) was 1.7% (-1.4% to 4.7%).ConclusionsDiscordance between animal and human studies may be due to bias or to the failure of animal models to mimic clinical disease adequately.
| S-EPMC1781970 | biostudies-literature
Project description:Background: There is a steadily growing number of different reconstructive surgical procedures for hypospadias that were tested on animal models prior to their human application. However, the clinical translatability and reproducibility of the results encountered in preclinical urethral reconstruction experiments is considered poor, with significant factors contributing to the poor design and reporting of animal experiments. Our objective was to evaluate the quality of the design and reporting in published articles of urethral reconstructive preclinical studies. Methods: Both PubMed and EMBASE databases were searched for animal urethral repair experiments between January 2014 and September 2019. Internal quality (bias) was evaluated through several signaling questions arising from the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE), while the quality of reporting was assessed by the Animal Research: Reporting of In vivo Experiments (ARRIVE) guidelines by scoring of a 20-item checklist. Results: A total of 638 articles were initially screened after the literature search. Employing the inclusion and exclusion criteria, 30 studies were chosen for full-text screening and 21 studies were considered eligible for the quality assessment. The mean score of the checklist was 66%. The elements that accomplished the highest grades included the number of animals utilized, the number in each investigational and control group, and the delineation of investigational conclusions. The items that were least commonly stated comprised information about the experimental method, housing and husbandry, rationalization of the number of animals, and reporting of adverse events. No paper stated the sample size estimation. Conclusion: We found that several critical experiment design principles were poorly reported, which hinders a rigorous appraisal of the scientific quality and reproducibility of the experiments. A comprehensive implementation of the ARRIVE guidelines in animal studies exploring urethral repair is necessary to facilitate the effective translation of preclinical research findings into clinical therapies.
| S-EPMC8386350 | biostudies-literature
Project description: Not available
| S-EPMC1122396 | biostudies-literature
Project description:IntroductionDiscrete choice experiments (DCEs) have been used to measure patient and healthcare professionals preferences in a range of settings internationally. Using DCEs in primary care is valuable for determining how to improve rational shared decision making. The purpose of this systematic review is to assess the validity of the methods used for DCEs assessing the decision making of healthcare professionals in primary care.Main bodyA systematic search was conducted to identify articles with original data from a discrete choice experiment where the population was primary healthcare professionals. All publication dates from database inception to 29th February 2020 were included. A data extraction and validity assessment template based on guidelines was used. After screening, 34 studies met the eligibility criteria and were included in the systematic review. The sample sizes of the DCEs ranged from 10 to 3727. The published DCEs often provided insufficient detail about the process of determining the attributes and levels. The majority of the studies did not involve primary care healthcare professionals outside of the research team in attribute identification and selection. Less than 80% of the DCEs were piloted and few papers investigated internal or external validity.ConclusionsFor findings to translate into improvements in rational shared decision making in primary care DCEs need to be internally and externally valid and the findings need to be able to be communicated to stakeholders in a way that is understandable and relevant.
| S-EPMC7725112 | biostudies-literature
Project description:ObjectiveTo conduct a systematic review of studies reporting on the validity of International Classification of Diseases (ICD) codes for identifying stroke in administrative data.MethodsMEDLINE and EMBASE were searched (inception to February 2015) for studies: (a) Using administrative data to identify stroke; or (b) Evaluating the validity of stroke codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), or Kappa scores) for stroke, or data sufficient for their calculation. Additional articles were located by hand search (up to February 2015) of original papers. Studies solely evaluating codes for transient ischaemic attack were excluded. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool.ResultsSeventy-seven studies published from 1976-2015 were included. The sensitivity of ICD-9 430-438/ICD-10 I60-I69 for any cerebrovascular disease was ? 82% in most [? 50%] studies, and specificity and NPV were both ? 95%. The PPV of these codes for any cerebrovascular disease was ? 81% in most studies, while the PPV specifically for acute stroke was ? 68%. In at least 50% of studies, PPVs were ? 93% for subarachnoid haemorrhage (ICD-9 430/ICD-10 I60), 89% for intracerebral haemorrhage (ICD-9 431/ICD-10 I61), and 82% for ischaemic stroke (ICD-9 434/ICD-10 I63 or ICD-9 434&436). For in-hospital deaths, sensitivity was 55%. For cerebrovascular disease or acute stroke as a cause-of-death on death certificates, sensitivity was ? 71% in most studies while PPV was ? 87%.ConclusionsWhile most cases of prevalent cerebrovascular disease can be detected using 430-438/I60-I69 collectively, acute stroke must be defined using more specific codes. Most in-hospital deaths and death certificates with stroke as a cause-of-death correspond to true stroke deaths. Linking vital statistics and hospitalization data may improve the ascertainment of fatal stroke.
| S-EPMC4546158 | biostudies-literature
Project description:Objective: Exercise is reported to be beneficial for breast cancer. However, the results seem inconsistent. We conducted this systematic review and meta-analysis of animal experimental studies to fully understand the effect of exercise on breast cancer in animal model. Methods: We searched databases from inception to April 2022 and manually searched related references to retrieve eligible studies. We screened eligible studies and extracted related data. We assessed the risk of bias and reporting quality using the SYstematic Review Centre for Laboratory animal Experimentation Risk of Bias tool and the Animal Research: Reporting of In Vivo Experiments guidelines 2.0, respectively. We summarized the study characteristics and findings of included studies and conducted meta-analysis with RevMan software. Subgroup analysis and sensitivity analysis were also performed. Results: We identified 537 potential literatures and included 47 articles for analysis. According to the results of risk of bias assessment, only selective outcome reporting was in low risk of bias. Items of sequence generation, random outcome assessment, and incomplete outcome data were rated as high risk of bias. Most of other items were rated unclear risk of bias. In reporting quality assessment, all included articles reported grouping method and experimental procedures. However, no study provided information of the study protocol registration. Meta-analysis showed that, compared with sedentary lifestyle, exercise reduced more tumor weight (MD = −0.76, 95%CI −0.88 to −0.63, p = 0.85, I2 = 0%) and tumor number per animal (MD = −0.61, 95%CI −0.91 to −0.31, p = 0.34, I2 = 8%). Exercise decreased more tumor incidence than sedentary lifestyle both in motorized wheel/high-intensity (OR = 0.22, 95%CI 0.11 to 0.46, p = 0.09, I2 = 41%) and free wheel/low-intensity treadmill running (OR = 0.45, 95%CI 0.14 to 1.44, p = 0.04, I2 = 60%). Sensitivity analysis showed that the results were robust. Conclusion: Exercise could reduce tumor weight, number of tumors per animal, and incidence of tumor in breast cancer model of mice and rats. However, the risk of bias items and reporting guidelines in preclinical studies should be concerned. Future research should consider standards of conducting and reporting preclinical studies and choose suitable exercise protocol for higher quality evidence of exercise for breast cancer.
| S-EPMC9208379 | biostudies-literature
Project description:BackgroundOptimal outcomes after large-vessel occlusion (LVO) stroke are highly dependent on prompt diagnosis, effective communication, and treatment, making LVO an attractive avenue for the application of artificial intelligence (AI), specifically machine learning (ML). Our objective is to conduct a systematic review to describe existing AI applications for LVO strokes, delineate its effectiveness, and identify areas for future AI applications in stroke treatment and prognostication.MethodsA systematic review was conducted by searching the PubMed, Embase, and Scopus databases. After deduplication, studies were screened by title and abstract. Full-text studies were screened for final inclusion based on prespecified inclusion and exclusion criteria. Relevant data were extracted from each study.ResultsOf 11,512 resultant articles, 40 were included. Of 30 studies with reported ML algorithms, the most commonly used ML algorithms were convolutional neural networks in 10 (33.3%), support vector machines in 10 (33.0%), and random forests in 9 (30.0%). Studies examining triage favored direct transport to a stroke center and predicted improved outcomes. ML techniques proved vastly accurate in identifying LVO on computed tomography. Applications of AI to patient selection for thrombectomy are lacking, although some studies determine individual patient eligibility for endovascular treatment with high accuracy. ML algorithms have reasonable accuracy in predicting clinical and angiographic outcomes and associated factors.ConclusionsAI has shown promise in the diagnosis and triage of patients with acute stroke. However, the role of AI in the management and prognostication remains limited and warrants further research to help in decision support.
| S-EPMC9172262 | biostudies-literature