Table 1.

Select features of low-dosage challenge studies as compared with higher-dosage challenge studies, and the authors’ assessment of them as advantages (+ or ++), disadvantages (–) or neutral (0).

Feature		Authors’ assessment	Comments
Pragmatic considerations	Shorter time to start	++	/
	Likelihood to start	++	/
	Larger financial cost and additional logistics	–	Less acute, given high investment in COVID-19 vaccine research
Scientific considerations	Avoiding type II errors of ruling out efficacious vaccines	++	/
	Avoiding type I errors of not ruling out inefficacious vaccines	0/–	Can be avoided if study is followed by a field trial, or by testing in a branching model together with high-dosage challenges
	External validity	0/+	Higher when there is standardization across multiple sites
Ethical considerations	Reducing risk to individuals	++	Risk reduction due to reduced infection risk and (possibly) dose-severity relationship
	Reducing risk to cohort	0	Unclear whether risk to cohort is higher or lower than conventional challenge trial; commensurate cohort risks with field trial