Study logistics that can impact medical countermeasure efficacy testing in mouse models of radiation injury

Figures & data

Table 1. Important confounders to consider when planning murine radiation studies.

Confounder	Potential Impact	Mitigation Strategy
Study variables
Exposure model	High	Review literature to select appropriate model for study and Identify optimum radiation exposure dosing for the model
Timing of irradiation	High	Irradiate animal cohorts at the same time of day and within a 3–4 hour window
Statistics	Moderate	Minimize bias with blinded studies, ensure animal numbers in each study arm are sufficient to provide statistical power
Animal variables
Age at time of irradiation	High	Use animals consistently within a narrow age range (1–2 weeks) and be aware that younger and older animals may have different radiation sensitivity
Sex	High	Conduct studies in both male and female animals and compare data
Strain	Moderate	Select strain appropriate for study design (e.g. prone to develop endpoint of interest), establish radiation dose response curves for selected exposure model
Seasonality	Low	Transport conditions at different times of year may impact study outcomes so plan studies with this information in mind
Vendor	Moderate	When possible, order animals from one breeding room at one vendor site
Husbandry variables
Diet and nutritional access	Moderate	Investigate chow ingredients and possible impact of known dietary mitigators; be aware of dental injuries and assist animals unable to access standard chow
Housing (single vs. group)	Moderate	Group animals in cages when possible; combine animals from different treatment arms in the same cage to avoid bias
Animal handling	Moderate	Minimize handling of irradiated animals; consider weighing less frequently
Use of anesthesia	Moderate	Minimize anesthesia use, irradiate within a jig so not needed during exposure
Route of administration	Moderate	Minimize number of injections; rotate injection volumes and sites; Limit gavage use post-irradiation
Medical management
Water (e.g. acidified)	Moderate	Determine facility water source and report in publications
Antibiotics use	Moderate	Understand potential mitigation of radiation lethality with selected antibiotic(s)
Euthanasia criteria	High	Establish prior to study; Individuals assessing animal status Should be independent
Radiation variables
Source	Low	Ensure same irradiator/radiation type is used throughout a study. Be aware of irradiators used in other studies when attempting comparisons
Exposure geometry	Medium	Consider directionality and orientation of animals relative to radiation source; Report exposure geometries in publications
Dose rate	Medium	Maintain a consistent dose rate across studies; avoid very high or very low dose rates for MCM efficacy studies to enable comparison with other research
Shielding	High	Measure exposures in shielded areas with dosimetry; Report details of shielding in publications
Radiation dosimetry	High	Consider pre-/in-run-/post-exposure dosimetry as appropriate, to ensure correct dosing; report methods in publications