. 2012 Nov 9;11:372. doi: 10.1186/1475-2875-11-372

Table 1.

Considerations of different field trial design options for second-generation malaria vaccines

Field efficacy trial options	2^ndgeneration vs placebo	2^ndgeneration vs 1^stgeneration	1^st/2^ndgeneration vs 1^stgeneration	1^st/2^ndgeneration vs 1^stgeneration vs placebo
Estimate of efficacy	Absolute efficacy estimated.	Relative efficacy estimated.	Relative efficacy estimated.	Absolute and relative efficacy estimated.
Type of assessment	Superiority to no treatment.	Non-inferiority to 1^st generation or superiority to 1^st generation.	Superiority to 1^st generation.	Superiority to 1^st generation and to no treatment.
Limitations and Considerations	May be considered unethical to randomize to placebo, if 1^st generation vaccine is available and recommended.	Large sample sizes may be needed. Non-inferiority design would not show progress towards the 80% effective goal in the label, but could make alternative vaccines available.	Large sample sizes may be needed. 1^st and 2^nd generation vaccines could be given together or as prime-boost strategy.	Very large sample sizes may be needed (may not be feasible). May be considered unethical to randomize to placebo, if 1st generation vaccine is available and recommended. This design would not demonstrate efficacy of the 2^nd generation vaccine independent of the 1^st generation vaccine.
	Efficacy relative to 1st generation vaccine would not be known	Efficacy relative to no treatment would not be known.	Efficacy relative to no treatment would not be known.