Jones Mark A, Graves Todd, Middleton Bianca, Totterdell James, Snelling Thomas L, Marsh Julie A
Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids InstituteUniversity of Western Australia, Perth, 6009, WA, Australia.
Berry Consultants, 3345 Bee Caves Rd Suite 201, Austin, 78746, TX, USA.
Trials. 2020 Aug 26;21(1):741. doi: 10.1186/s13063-020-04602-w.
The purpose of this double-blind, randomised, placebo-controlled, adaptive design trial with frequent interim analyses is to determine if Australian Indigenous children, who receive an additional (third) dose of human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to < 12 months, would improve protection against clinically significant all-cause gastroenteritis.
Up to 1000 Australian Aboriginal and Torres Strait Islander (hereafter Indigenous) infants aged 6 to < 12 months will be recruited from all regions of the Northern Territory.
The intervention is the addition of a third scheduled dose of human monovalent rotavirus vaccine.
CO-PRIMARY AND SECONDARY OUTCOME MEASURES: ORVAC has two co-primary outcomes: (1) anti-rotavirus IgA seroconversion, defined as serum anti-rotavirus IgA ≥ 20 U/ml 28 to 55 days post Rotarix/placebo, and (2) time from randomisation to medical attendance for which the primary reason for presentation is acute gastroenteritis or acute diarrhoea illness before age 36 months. Secondary outcomes include (1) change in anti-rotavirus IgA log titre, (2) time from randomisation to hospitalisation with primary admission code presumed or confirmed acute diarrhoea illness before age 36 months, (3) time from randomisation to hospitalisation for which the admission is rotavirus confirmed diarrhoea illness before age 36 months and (4) time from randomisation to rotavirus infection (not necessarily requiring hospitalisation) meeting the jurisdictional definition before age 36 months.
A detailed, prospective statistical analysis plan is presented for this Bayesian adaptive design. The plan was written by the trial statistician and details the study design, pre-specified adaptative elements, decision thresholds, statistical methods and the simulations used to evaluate the operating characteristics of the trial. As at August 2020, four interim analyses have been run, but no stopping rules have been triggered. Application of this SAP will minimise bias and supports transparent and reproducible research.
Clinicaltrials.gov NCT02941107. Registered on 21 October 2016 ORIGINAL PROTOCOL FOR THE STUDY: https://doi.org/10.1136/bmjopen-2019-032549.
本双盲、随机、安慰剂对照、采用频繁中期分析的适应性设计试验旨在确定，对于6至未满12个月的澳大利亚原住民儿童，额外接种一剂（第三剂）人轮状病毒疫苗（Rotarix，葛兰素史克公司生产）是否能增强对具有临床意义的全因性肠胃炎的防护作用。
将从北领地所有地区招募多达1000名6至未满12个月的澳大利亚原住民和托雷斯海峡岛民（以下简称原住民）婴儿。
干预措施为额外接种一剂预定的单价人轮状病毒疫苗。
ORVAC有两个共同主要结局指标：（1）抗轮状病毒IgA血清阳转，定义为接种Rotarix/安慰剂后28至55天血清抗轮状病毒IgA≥20 U/ml；（2）从随机分组至因急性肠胃炎或急性腹泻疾病而就医的时间，该疾病为36个月龄前就医的主要原因。次要结局指标包括：（1）抗轮状病毒IgA对数滴度的变化；（2）从随机分组至因疑似或确诊为急性腹泻疾病而住院的时间，该疾病为36个月龄前住院的主要原因；（3）从随机分组至因确诊为轮状病毒腹泻疾病而住院的时间，该疾病为36个月龄前住院的主要原因；（4）从随机分组至符合辖区定义的轮状病毒感染（不一定需要住院）的时间，该感染发生在36个月龄前。
针对此贝叶斯适应性设计给出了一份详细的前瞻性统计分析计划。该计划由试验统计学家撰写，详细说明了研究设计、预先指定的适应性要素、决策阈值、统计方法以及用于评估试验操作特征的模拟。截至2020年8月，已进行了四次中期分析，但未触发任何停止规则。应用此统计分析计划将使偏差最小化，并支持透明且可重复的研究。
Clinicaltrials.gov NCT02941107。于2016年10月21日注册。研究原始方案：https://doi.org/10.1136/bmjopen-2019-032549。
