A cluster-randomised, non-inferiority trial of the impact of a two-dose compared to three-dose schedule of pneumococcal conjugate vaccination in rural Gambia: the PVS trial.
A cluster-randomised, non-inferiority trial of the impact of a two-dose compared to three-dose schedule of pneumococcal conjugate vaccination in rural Gambia: the PVS trial.
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DOI：
10.1186/s13063-021-05964-5
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发表时间：
2022-01-24
期刊：
影响因子：
2.5
通讯作者：
Greenwood B
中科院分区：
文献类型：
--
作者：
Mackenzie GA;Osei I;Salaudeen R;Hossain I;Young B;Secka O;D'Alessandro U;Palmu AA;Jokinen J;Hinds J;Flasche S;Mulholland K;Nguyen C;Greenwood B
肺炎球菌结合疫苗（PCV）可有效预防肺炎球菌疾病，但PCV的成本阻碍了肺炎球菌疫苗接种的全球影响。在中等收入和低收入国家，如冈比亚，减少剂量方案试验的相关性和可行性最大，在那里，PCV已被引入，疾病控制良好，但疫苗型肺炎球菌的传播仍然存在。我们正在进行一项大型的随机分组、非劣效性、田间试验，研究PCV的替代剂量减少方案与标准方案PVS试验相比。PVS是一项前瞻性、随机分组、非劣效性、真实世界田间试验，旨在比较计划在6周龄时给予1剂PCV，在9月龄时给予加强剂量的替代方案（即替代“1 + 1”方案）与计划在6、10和14周龄时给予3剂主要剂量的标准方案（即标准“3 + 0”方案）。干预措施将持续4年。主要终点是试验第4年2周至59个月临床肺炎儿童中鼻咽疫苗型肺炎球菌携带的人群水平患病率。受试者和现场工作人员不对组分配设盲，而实验室终点的测量将设盲。按照1：1的比例，将68个地理人口组随机分配到每一个时间表，所有常住婴儿都有资格登记。所有5岁以下的住院儿童都在11个卫生设施进行持续监测，以确定临床安全终点;侵袭性肺炎球菌疾病、放射性肺炎、临床肺炎和住院治疗。次要终点包括第2年和第4年鼻咽疫苗型肺炎球菌携带的人群水平患病率，以及第4年6-12周龄未免疫婴儿的疫苗型携带患病率。该试验包括数学建模，卫生经济学和卫生系统研究的组成部分。分析将考虑到按群组进行的测量的潜在非独立性，比较两个时间表对人口水平的影响和个人水平的解释。非劣效性界值由替代方案与标准方案相比的“可接受效应损失”确定。次要终点将提供大量证据支持主要终点的解释。PVS将评估从标准3+ 0方案过渡到替代1 + 1方案在肺炎球菌高传播环境中的效果。PVS的结果将为全球决策提供关于使用减少剂量PCV计划的信息。国际标准随机对照试验编号15056916。于2018年11月15日注册。在线版本包含补充材料，可通过10.1186/s13063-021-05964-5获得。
Pneumococcal conjugate vaccines (PCV) effectively prevent pneumococcal disease but the global impact of pneumococcal vaccination is hampered by the cost of PCV. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where PCV has been introduced with good disease control but where transmission of vaccine-type pneumococci persists. We are conducting a large cluster-randomised, non-inferiority, field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial. PVS is a prospective, cluster-randomised, non-inferiority, real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative ‘1 + 1’ schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. the standard ‘3 + 0’ schedule). The intervention will be delivered for 4 years. The primary endpoint is the population-level prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2 weeks to 59 months with clinical pneumonia in year 4 of the trial. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoint will be masked. Sixty-eight geographic population clusters have been randomly allocated, in a 1:1 ratio, to each schedule and all resident infants are eligible for enrolment. All resident children less than 5 years of age are under continuous surveillance for clinical safety endpoints measured at 11 health facilities; invasive pneumococcal disease, radiological pneumonia, clinical pneumonia, and hospitalisations. Secondary endpoints include the population-level prevalence of nasopharyngeal vaccine-type pneumococcal carriage in years 2 and 4 and vaccine-type carriage prevalence in unimmunised infants aged 6–12 weeks in year 4. The trial includes components of mathematical modelling, health economics, and health systems research. Analysis will account for potential non-independence of measurements by cluster, comparing the population-level impact of the two schedules with interpretation at the individual level. The non-inferiority margin is informed by the ‘acceptable loss of effect’ of the alternative compared to the standard schedule. The secondary endpoints will provide substantial evidence to support the interpretation of the primary endpoint. PVS will evaluate the effect of transition from a standard 3+ 0 schedule to an alternative 1 + 1 schedule in a setting of high pneumococcal transmission. The results of PVS will inform global decision-making concerning the use of reduced-dose PCV schedules. International Standard Randomised Controlled Trial Number 15056916. Registered on 15 November 2018. The online version contains supplementary material available at 10.1186/s13063-021-05964-5.
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影响因子：
4.2
作者：
Althouse BM;Hammitt LL;Grant L;Wagner BG;Reid R;Larzelere-Hinton F;Weatherholtz R;Klugman KP;Rodgers GL;O'Brien KL;Hu H
通讯作者：
Hu H
影响因子：
3.7
作者：
de Waroux, O. le Polain;Cohuet, S.;Edmunds, W. J.
通讯作者：
Edmunds, W. J.
影响因子：
168.9
作者：
Cutts, FT;Zaman, SMA;Adegbola, RA
通讯作者：
Adegbola, RA
影响因子：
56.3
作者：
Mackenzie, Grant A.;Hill, Philip C.;Corrah, Tumani
通讯作者：
Corrah, Tumani
影响因子：
168.9
作者：
Hammitt, Laura L.;Etyang, Anthony O.;Scott, J. Anthony G.
通讯作者：
Scott, J. Anthony G.