Table 2.

Scenarios encountered in the design of Phase 1 preventive HIV vaccine clinical trials, and corresponding decisions regarding the inclusion of placebo recipients.

Decision	Scenarios
Placebo recipients are highly advantageous to include	• If a fair assessment of subjective safety/tolerability endpoints is required, and there are insufficient data on safety/tolerability of the same vaccine candidate in a similar study population.
	OR
	• If measurements of study endpoints may be influenced by infectious exposures after study entry.
Placebo recipients may not be included	• If there are sufficient data on safety/tolerability of the same vaccine candidate in a similar study population,
	AND
	• If baseline specimens are feasible and appropriate to serve as controls for immunogenicity assessments.
Placebo recipients are helpful, but not essential to include	• If some study endpoints are measured by assays or tools that will benefit from further validation based on more placebo recipient samples,
	OR
	• If the characterization of non-vaccine-induced immunological measurements in placebo recipients will aid the interpretation of those measurements in vaccine recipients.