Table 4.

Exploratory versus therapeutic preclinical studies

Goal	Exploratory studies: mechanism/target-focused	Therapeutic studies: compound-focused
Study design	Efficacy data should be assessed through multiple outcome measures.	Efficacy results should be demonstrated in more than one model.
	Both exploratory and therapeutic studies should be randomized, placebo-controlled, and blinded, with a dose response.
	In vivo model considerations for both types of studies include pathogenic stage, age, length of treatment required, and exclusion criteria.
ADME	Studies should include initial physicochemical property considerations and terminal blood and brain tissue sampling for assurance of target exposure and possible pharmacokinetics verification.	Studies should include ADME profiling, full pharmacokinetics/pharmacodynamics analysis and distribution/exposure of parent compound and metabolites.
Toxicity	Defined toxicity assessment is not needed, but a simple drug tolerability assay should be included.	Toxicology should be assessed in the model being studied, with treatment conducted at levels reliably below adverse event doses.
Statistics plan	While statistical considerations need not be as stringent, prospective power analysis should take into account variability in the model itself and in outcome measure readouts.	Prospective study design should include sample size power analyses, statistical evaluation plan, primary and secondary outcome measures, blinding, and randomization.

ADME, absorption, distribution, metabolism, and excretion.