Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example

Table 4 Hemagglutination-inhibition antibody response at 21 days following vaccination (ATP cohort subset for immunogenicity)

			Influenza A (H1N1) A/New Caledonia/20/99 (H1N1) IVR-116		Influenza A (H3N2) A/New York/55/2004 (H3N2) X-157		Influenza B B/Jiangsu/10/2003 virus
	CHMP acceptance criteria**	CBER acceptance criteria***	TIV N = 632	Placebo N = 315	TIV N = 632	Placebo N = 315	TIV N = 632	Placebo N = 315
Geometric Mean Titer (GMT)	No Standard	No Standard	730.5 [648.1–823.3]	11.6 [10.2–13.3]	131.7 [119.9–144.6]	13.5 [11.9–15.3]	191.1 [175.7–207.9]	17.9 [15.7–20.3]
% Sero-conversion rate *	% > 40%	LL of 95% CI > 40%	89.2 [86.6–91.5]	0.0 [0.0–1.2]	77.2 [73.7–80.4]	0.3 [0.0–1.8]	82.9 [79.7–85.8]	0.0 [0.0–1.2]
% Sero-protection (titer ≥ 40)	% > 70%	LL of 95% CI > 70%	97.8 [96.31–98.78]	21.9 [17.46–26.88]	88.1 [85.35–90.55]	22.5 [18.04–27.56]	95.9 [94.03–97.30]	30.2 [25.14–35.56]

* Seroconversion rate for Hemagglutination-inhibition antibody response is defined as the percentage of vaccinees who have a prevaccination titer < 1:10 and a post-vaccination titer ≥ 1:40, or who have a prevaccination titer ≥ 1:10 and at least a fourfold increase in post-vaccination titer

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