Table 1.
Aspect of study | Preferred study design and reporting practices |
---|---|
Experimental design | Describe the species, strains, and genetic background, if known, for both experimental groups and controls |
Justification of selected animal models or experimental setting | |
Statement of adherence to ethical and animal care guidelines | |
Justification for route of treatment delivery/dosing | |
Report the timing of treatment delivery in regards to time of the day and endpoint assessment | |
Justification of the timing of treatment based on expected PK-PDs or anticipated time of action of the treatment in the studied strain | |
Use consistent housing, breeding and handling conditions across groups | |
Randomized, placebo/vehicle-controlled, blinded design | |
State criteria for dose selection; dose-response studies may inform on therapeutic window | |
Age, sex, stage of the disease, length of treatment and observation for outcomes, and other covariants that may affect outcomes (handling, litter effect etc) to be randomly distributed across groups | |
Apply uniform handling procedures across groups | |
Inclusion of methods to assess target relevance and target engagement | |
Select outcomes that are appropriate for the symptom/disease target or target population | |
Select measurable and quantifiable endpoints that allow rigorous objective comparisons | |
The purity, stability, manufacturing reproducibility of selected biologicals (viruses, cell lines, etc) should be described | |
Data collection and analysis | Describe the power analyses that set the sample size requirements |
Pre-define and report the inclusion and exclusion criteria and criteria for outliers | |
Pre-define and report rules for sampling data or stopping data collection | |
Describe causes and extent of lost data | |
Report interim analyses | |
Report number of replicates per group and statistics for each experiment; clarify if replicates are biological or technical and from how many experiments or animals they are derived from | |
Report the reproducibility of results across the experiments in the study and the distribution of values (scattergrams), if possible | |
Description and justification of the selected statistical methods | |
Minimizing bias | Data collection and analyses to be done blinded to group allocation |
Description of blinding methods and randomization of groups; report issues that hinder blinding | |
Strategies for randomization and/or stratification to be described | |
Inclusions and exclusions to be applied blindly to group allocation | |
Report missing data | |
Report both positive and negative data | |
Report conflicts of interests | |
Reporting of results | Experimental methods need to be described in sufficient detail to permit replication |
Describe housing, breeding and handling conditions: light/dark cycle, number of animals per cage, time of day of the experiment, type and sequence of experimental procedures per rat or group | |
Information on materials, tests, and assays used should be included to support their validation for their specificity and appropriateness for the studied population and study aims | |
Describe vehicle composition and any properties that might influence the demonstrated efficacy and tolerability of the AET | |
Report number of replicates per group and statistics for each experiment | |
Interpretation | Discuss clinical relevance of findings: target population, clinical applicability of treatment protocol (therapeutic window, tolerability of recommended doses, prior positive or adverse clinical experience with similar treatments) |
Discuss evidence for target relevance and target engagement | |
Discuss evidence for reproducibility, robustness or limitations of current study | |
Discuss effect size in regards to potential clinical impact | |
Discuss evidence in favor or against replication/validation of results | |
Discuss alternative interpretations of the findings | |
Discuss available concurring or discordant studies from the literature |
These recommendations are discussed extensively in several recent publications (Galanopoulou, Buckmaster, Staley, Moshe, Perucca, Engel, Loscher, Noebels, Pitkanen, Stables, White, O'Brien and Simonato 2012, Hooijmans, et al. 2010, Kahle and Bix 2012, Kilkenny, et al. 2010, Landis, Amara, Asadullah, Austin, Blumenstein, Bradley, Crystal, Darnell, Ferrante, Fillit, Finkelstein, Fisher, Gendelman, Golub, Goudreau, Gross, Gubitz, Hesterlee, Howells, Huguenard, Kelner, Koroshetz, Krainc, Lazic, Levine, Macleod, McCall, Moxley, Narasimhan, Noble, Perrin, Porter, Steward, Unger, Utz and Silberberg 2012, Ludolph, et al. 2010, Nature Neuroscience 2013, Rigor in Science Working Group 2011, Shineman, et al. 2011)