Evidence-based preclinical medicine最新文献

The concepts of effect size and statistical power are often disregarded in basic neuroscience, and most articles in the field draw their conclusions solely based on the arbitrary significance thresholds of statistical inference tests. Moreover, studies are often underpowered, making conclusions from significance tests less reliable. With this in mind, we present the protocol of a systematic review to study the distribution of effect sizes and statistical power in the rodent fear conditioning literature, and to analyse how these factors influence the description and publication of results. To do this, we will conduct a search in PubMed for “fear conditioning” AND “mouse” OR “mice” OR “rat” OR “rats” and obtain all articles published online in 2013. Experiments will be included if they: (1) describe the effect(s) of a single intervention on fear conditioning acquisition or consolidation; (2) have a control group to which the experimental group is compared; (3) use freezing as a measure of conditioned fear and (4) have available data on mean freezing, standard deviation and sample size of each group and on the statistical significance of the comparison. We will use the extracted data to calculate the distribution of effect sizes in these experiments as well as the distribution of statistical power curves for detecting a range of differences at a threshold of α = 0.05. We will assess correlations between these variables and (1) the chances of a result being statistically significant, (2) the way the result is described in the article text, (3) measures to reduce risk of bias in the article and (4) the impact factor of the journal and the number of citations of the article. We will also perform analyses to see whether effect sizes vary systematically across species, gender, conditioning protocols or intervention types.

The increasing prevalence of Alzheimer's disease (AD) poses a considerable socio-economic challenge. Decades of experimental research have not led to the development of effective disease modifying interventions. A deeper understanding of in vivo research might provide insights to inform future in vivo research and clinical trial design. We therefore performed a systematic review and meta-analysis of interventions tested in transgenic mouse models of AD. We searched electronically for publications testing interventions in transgenic models of AD. We extracted data for outcome, study characteristics and reported study quality and calculated summary estimates of efficacy using random effects meta-analysis. We identified 427 publications describing 357 interventions in 55 transgenic models, involving 11,118 animals in 838 experiments. Of concern, reported study quality was relatively low; fewer than one in four publications reported the blinded assessment of outcome or random allocation to group and no study reported a sample size calculation. Additionally, there were few data for any individual intervention—only 16 interventions had outcomes described in 5 or more publications. Finally, “trim and fill” analyses suggested one in seven pathological and neurobehavioural experiments remain unpublished. Given these historical weaknesses in the in vivo modelling of AD in transgenic animals and the identified risks of bias, clinical trials that are based on claims of efficacy in animals should only proceed after a detailed critical appraisal of those animal data.

Targeted temperature management (TTM) of 32–34 °C has been the standard treatment for out-of-hospital cardiac arrest since clinical trials in 2002 showed benefits to survival and neurological outcome. Recently, this treatment has been challenged by another clinical trial showing no difference in outcome between TTM of 33 °C and 36 °C. This protocol describes the methodology for a meta-analysis detailing temperature-reducing interventions to treat global ischaemia in animal models. By combining relevant data sets in the literature, we will explore the experimental evidence for TTM. Our aims are to explain possible translational gaps and provide methodological considerations for future experimental research and clinical trials.

Aneurysmal subarachnoid haemorrhage (SAH) is a type of stroke causing up to 70% of patients to either die or be dependent on others at six months. Delayed cerebral ischaemia (DCI) is the most important cause of poor outcome after the initial injury. Oral nimodipine is the only pharmaceutical treatment with proven benefits and alternative therapies are needed. There are strong associations between DCI and cerebral vessel narrowing but interventions to treat DCI by improving vessel narrowing have been largely ineffective. Alpha-calcitonin gene-related peptide (αCGRP) is a potent microvascular vasodilator which may be effective in treating DCI by preventing cerebral vessel narrowing after SAH. This protocol outlines the methodology for a systematic review and meta-analysis investigating the effect of αCGRP on cerebral vessel narrowing and neurological outcomes after SAH from in vivo animal studies.

Despite many efforts by the research community, Alzheimer's disease (AD) is still an incurable neurodegenerative condition that affects an estimated 44 million individuals worldwide and this figure is expected to increase to 135 million by the year 2050. As the research community currently reflects on previous endeavours, it is essential that we maximize the use of existing knowledge to inform future trials in the field. This article describes the development of a systematically identified data set relating to over 300 interventions tested in over 10,000 animals. The data set includes cohort-level information for six structural outcomes and six behavioural assessments. We encourage others to use this dataset to inform the design of future animal experiments modelling AD and to promote effective translation to human health.

Cardiac-derived stem or progenitor cells (CSCs) have emerged as a possible therapeutic intervention for myocardial infarction, potentially ameliorating the devastating effects caused by inadequate blood flow to the heart. The first human clinical trials using these myocardial-derived cells have recently started, but scientific controversy exists regarding the efficacy and origin of some of these stem cells in preclinical animal models. Systematic review of the current literature on CSCs in ischaemic cardiomyopathy can provide useful additional information on the use of CSCs in preclinical trials. By combining all available data, we can adequately compare the different types of cells being used and possibly identify factors that influence cardiac stem cell therapy in general. This protocol provides a thorough description of the methodology that will be used in our systematic review and meta-analysis of all preclinical animal studies involving cardiac stem cell treatment for ischaemic cardiomyopathy.

Systematic reviews are an important method to support evidence-based decisions in healthcare (research). Although not yet as common as clinical systematic reviews, the number of systematic reviews of animal studies has been increasing steadily in recent years. An important method to promote high-quality systematic reviews is to pre-specify the review methodology in a protocol, before the conduct of the systematic review itself. In contrast to clinical systematic reviews, a standard protocol format for systematic reviews of animal studies is not yet available. Here, we present a protocol format tailored to the preparation, registration and publication of systematic reviews of animal intervention studies (i.e. systematic reviews of animal experiments studying the efficacy and/or safety of interventions intended for use in human patients). In analogy to the Cochrane review protocol, the format helps authors predefine the methodological approach of their systematic review, from research question to data synthesis. We recommend that authors prospectively complete and agree on the protocol, and register and/or publish it to allow feedback on the proposed methodology and to avoid the introduction of bias during the review process. Opportunities for obtaining feedback, and for registration and publication of review protocols are also discussed.