George Institute for Global Health, Sydney, NSW, Australia.
Crit Care Resusc. 2012 Mar;14(1):44-52.
The Crystalloid Versus Hydroxyethyl Starch Trial (CHEST) is a 7000-patient, multicentre, randomised controlled trial comparing the effects of 6% hydroxyethyl starch (130/0.4) to normal saline for fluid resuscitation in intensive care patients. The trial design is based on the Saline Versus Albumin Fluid Evaluation (SAFE) study and will be the largest fluid resuscitation trial conducted to date.
In accordance with two other trials conducted by the investigators, a predetermined statistical analysis plan (SAP) has been described and made public before completion of patient recruitment and data collection. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of study findings.
The SAP was designed by the chief investigators and statisticians and approved by the CHEST Management Committee. All authors were blind to treatment allocation and to the unblinded data produced during two interim analyses conducted by the Data Safety and Monitoring Board. The data shells were produced from a previously published protocol. Statistical analyses are described in broad detail. Specifically, information relevant to baseline characteristics and processes of care were defined, and statistically relevant descriptive elements described, with appropriate comparisons between groups. Trial outcomes were selected, categorised into primary, secondary and tertiary outcomes, and appropriate statistical comparisons between groups were planned and described.
A standard SAP for CHEST was developed. A trial profile outline and list of mock tables were produced. Descriptions of analyses of baseline characteristics, processes of care, measures of efficacy and outcomes were described. Six prespecified subgroups were defined and statistical comparisons between groups in these subgroups were described. In addition, analyses of tertiary outcomes, including health economic and functional outcome assessment, were described.
We have developed a predetermined SAP for CHEST. This plan accords with high-quality standards of internal validity to minimise analysis bias.
晶体液与羟乙基淀粉试验（CHEST）是一项纳入 7000 例患者的多中心、随机对照试验，旨在比较 6%羟乙基淀粉（130/0.4）与生理盐水在重症监护患者液体复苏中的作用。该试验设计基于生理盐水与白蛋白液评价（SAFE）研究，并将成为迄今为止进行的最大规模的液体复苏试验。
根据研究者开展的另外两项试验，在完成患者招募和数据收集之前，已经描述并公开了一份预先确定的统计分析计划（SAP）。为避免因了解研究结果而导致分析偏倚，本试验将严格按照 SAP 进行最终数据分析。
SAP 由首席研究者和统计学家设计，并由 CHEST 管理委员会批准。所有作者在两次由数据安全和监测委员会进行的期中分析中均对治疗分配和盲法数据不知情。数据汇总表是根据先前发表的方案生成的。统计分析有广泛详细的描述。具体而言，定义了与基线特征和治疗过程相关的信息，并对组间的统计相关描述性元素进行了描述，同时对试验结局进行了选择，将其分为主要结局、次要结局和次要结局，并对组间的适当统计比较进行了计划和描述。
制定了 CHEST 的标准 SAP。制作了试验概况大纲和模拟表格列表。描述了基线特征、治疗过程、疗效评估指标和结局的分析。定义了 6 个预设亚组，并对这些亚组中的组间统计比较进行了描述。此外，还描述了包括卫生经济学和功能结局评估在内的三级结局分析。
我们制定了 CHEST 的预先确定的 SAP。该计划符合内部有效性的高质量标准，可最大程度地减少分析偏倚。
