| Rationale |
Provide a clinically relevant rationale for the study that addresses clinical need, target patient population, relevance of animal model to human syndrome, treatment choice, target mechanism (if known) Justify the selection of materials and methods (eg, species, strain, sex, age, animal model, treatment choice) and discuss their relevance to the human condition
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| Experimental design |
Provide statement of adherence to ethical and animal-care guidelines Use blinded, randomised, placebo-controlled, dose–response design Use balanced randomisation of covariants across experimental groups Use adequate sample size pre-specified on the basis of statistical power calculations Undertake appropriate statistical analysis, with pre-specified primary and secondary endpoints and significance levels adjusted for multiple testing Address study aspects that will be important for translation to future human clinical trials (eg, which specific population does the study address, what outcome measure does it affect, what will be the timepoint of intervention, and at what dose?)
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| Treatment delivery |
Specify the source, purity, stability, and manufacturing reproducibility of the selected chemicals or biologicals (viruses, cell lines, and so on) Specify criteria for dose selection and do dose–response studies to inform on therapeutic window. If possible, address the relevance to human dosing Justify the route and protocol of treatment delivery and dosing, based on clinical relevance, pharmacokinetics, and anticipated time of action of the treatment on its hypothesised target within the studied strain Provide evidence for target relevance and engagement, if possible
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| Outcome assessment |
Select clinically relevant and reliably quantifiable outcome measures that are appropriate for the symptom, disease target, and target population and allow rigorous objective comparisons Describe the readouts (eg, seizure events) with sufficient detail to allow replication Include methods that assess target relevance and engagement, if possible Include methods to assess the tolerability of a treatment in animals, and its side-effects or off-target effects Optimise use of video-EEG to best meet the study goals, animal model characteristics, and type of seizures studied
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| Data collection, analysis, and reporting |
Provide accurate description of animal characteristics (species, strains, genetic background, sex, age, and housing and breeding conditions), materials and methods for treatment preparation and administration, animal handling, and outcome assessment, to allow replication Select sample sizes on the basis of power analyses that consider the number of covariates, variability in outcomes and expected data losses (ie, animal mortality, technical issues) Describe experimental methods in sufficient detail to permit replication Specify the pre-set inclusion and exclusion criteria, blinding procedures, and criteria for outliers or to stop the study Describe and justify the analytical and statistical methods used, based on methods and goals Report interim analyses, replicates per group, and statistics used per experiment Minimise bias with masked data collection and analysis, reporting of positive, negative, or missing data
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| Interpretation |
Discuss clinical relevance and implications of findings Discuss results in the following contexts: the reported effect size and power of the study; the evidence for target relevance and engagement; and the evidence for target validation in the human epilepsy syndrome Discuss evidence for reproducibility, robustness, limitations, or alternative interpretations of study
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| Publication issues |
Report conflicts of interest of investigators Provide equal opportunity for the publication of positive and negative studies, and studies that aim to reproduce the findings in the same or a different model of seizures or epilepsy Provide a forum to report the results of preclinical studies that could not be completed, to allow their inclusion in meta-analyses
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