Table 3.

Comparison of phase 0/microdosing with traditional phase I approaches

	Phase 0/Microdosing (eIND)	Traditional Phase I (IND)
Therapeutic intent	None	Possible
Study of systemic tolerability	None	Yes
Proof of Mechanism	Possible (e.g., PET receptor binding and displacement)	Possible
Preclinical Package	Limited, variable; depends on extent of exposure to the test article and experimental goals	Full requirements
in vitro models	Full requirement	Full requirements
toxicology	Limited, variable	Full requirements
genotoxicology	None or limited	Full requirements
GMP	Flexible, depending on available preclinical information and route of administration (e.g., sterility ensured for IV route)	Full requirements
Regulatory Review	30‐day	30‐day
Usual Duration of Program	4‐12 months	12‐24 months
Cost of Program	$ 0.5‐0.75 M	$ 1.5‐2.5 M
Studies
size (typical)	4‐10 participants	6‐30 participants
duration (per participant)	1‐14 days*	6‐60 days*
number of study sites	Single	Single/Multiple
maximal dose	<MTD	MTD
exposure	Limited (see Table 1)	Multiple doses allowed
population	Healthy volunteers or patientsVulnerable populations	Usually health volunteers (unless toxicity risk is high, e.g., in oncology trials)

*on average, could be longer with longer half‐life drugs; MTD, maximum tolerated dose.