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
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
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DOI：
10.1186/1471-2334-9-2
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发表时间：
2009-01-17
影响因子：
3.7
通讯作者：
Devaster, Jeanne-Marie
中科院分区：
文献类型：
--
作者：
Beran, Jiri;Wertzova, Veronika;Devaster, Jeanne-Marie
背景资料：我们的目的是确定一种三价灭活裂解病毒流感疫苗（TIV）对培养确认的流感A和/或B在成人的有效性18至64岁的年龄在2005/2006赛季在CzechRepublic.Methods：6203例受试者随机接受TIV（N = 4137）或安慰剂（N = 2066）。样本量是基于假设的发病率为4%，这提供了90%的把握度来拒绝疫苗效力（VE）>= 45%的假设。通过主动（每两周一次电话联系）和被动（自我报告）监测发现流感样疾病病例（定义为发烧（口腔温度>= 37.8摄氏度）加上咳嗽和/或喉咙痛），并从受试者中收集鼻和喉咙拭子进行病毒培养。结果：TIV耐受性良好，并诱导良好的免疫反应。与整个欧洲一样，2005/2006年流感季节在研究地区异常温和，在研究队列中仅发现46例培养确诊病例（10例甲型流感和36例B型流感）。此外，在B分离株中，35株被鉴定为B/香港330/2001样（B/维多利亚/2/87谱系），与疫苗B毒株（B/Yamagata/16/88谱系）在抗原性上不相关。在疫苗组的攻击率（0.7%）是没有统计学意义上的攻击率在安慰剂组（0.9%）的差异。结论：由于在本研究中的流感季节的非典型性质，我们无法评估TIV的疗效。这一经验说明了在单一季节进行前瞻性流感疫苗有效性试验的挑战，因为流感发作率和流行毒株或B病毒谱系匹配的漂移可能难以提前估计。
Background: Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.Methods: 6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was >= 45%. Cases of influenza like illness (defined as fever (oraltemperature >= 37.8 degrees C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.Results: TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).Conclusion: Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.