Hui David, Zhukovsky Donna S, Bruera Eduardo
Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
J Pain Symptom Manage. 2015 Mar;49(3):625-31. doi: 10.1016/j.jpainsymman.2014.11.294. Epub 2014 Dec 30.
The difference in patient-reported outcomes between study arms can often be difficult to ascertain in randomized controlled trials (RCTs) using a parallel design because of wide interindividual variations in baseline characteristics and how patients interpret the outcome measures. Furthermore, the minimal clinically significant difference is often not available for many outcomes, and even when available, not individualized for each patient. Crossover RCTs are designed for intraindividual comparisons, which can address these issues by asking patients to directly compare the interventions with regard to effectiveness, adverse effects, and ease of use and to provide an overall choice.
We discuss the key design elements for crossover trials, their advantages and disadvantages relative to parallel designs, and their utility in palliative care research using a number of case examples.
This is a narrative review.
Crossover studies randomize patients to a sequence of treatments. In addition to facilitating intraindividual comparisons, they often require a smaller sample size for the same statistical power compared with parallel designs and are thus less costly. However, crossover studies are only feasible when the condition being studied is relatively stable and the intervention has a short-term effect. Crossover studies with inadequate washout periods may be difficult to interpret. The risk of attrition also may increase because of prolonged study duration.
By facilitating intraindividual comparisons and eliciting patient preferences, crossover studies can provide unique information on the superior intervention. Crossover designs should be considered for selected palliative care studies.
在采用平行设计的随机对照试验（RCT）中，由于基线特征存在广泛的个体差异以及患者对结局指标的解读方式不同，往往难以确定研究组间患者报告的结局差异。此外，许多结局指标通常没有最小临床显著差异，即便有，也未针对每个患者进行个体化设定。交叉RCT旨在进行个体内比较，通过要求患者直接比较干预措施在有效性、不良反应和易用性方面的情况并做出总体选择，从而解决这些问题。
我们使用多个案例讨论交叉试验的关键设计要素、相对于平行设计的优缺点及其在姑息治疗研究中的效用。
这是一篇叙述性综述。
交叉研究将患者随机分配到一系列治疗中。除了便于个体内比较外，与平行设计相比，在相同统计效能的情况下，交叉研究通常所需样本量较小，因此成本较低。然而，交叉研究仅在研究的疾病状况相对稳定且干预措施具有短期效果时才可行。洗脱期不足的交叉研究可能难以解读。由于研究持续时间延长，失访风险也可能增加。
通过便于个体内比较并引出患者偏好，交叉研究可以提供关于更优干预措施的独特信息。对于选定的姑息治疗研究，应考虑采用交叉设计。
