Public Health Sciences, Centre for Population Health Sciences, University of Edinburgh Medical School, Edinburgh, UK.
Clin Trials. 2010 Feb;7(1):44-57. doi: 10.1177/1740774509356580.
Clinical trials in traumatic brain injury have a disappointing track record, with a long history of 'negative' Phase III trials. One contributor to this lack of success is almost certainly the low efficiency of the conventional approach to the analysis, which discards information by dichotomizing an ordinal outcome scale.
Our goal was to evaluate the potential efficiency gains, which can be achieved by using techniques, which extract additional information from ordinal outcome data - the proportional odds model and the sliding dichotomy. In addition, we evaluated the additional efficiency gains, which can be achieved through covariate adjustment.
The study was based on simulations, which were built around a database of patient-level data extracted from eight Phase III trials and three observational studies in traumatic brain injury. Two different putative treatment effects were explored, one which followed the proportional odds model, and the other which assumed that the effect of the intervention was to reduce the risk of death without changing the distribution of outcomes within survivors. The results are expressed as efficiency gains, reported as the percentage reduction in sample size that can be used with the ordinal analyses without loss of statistical power relative to the conventional binary analysis.
The simulation results show substantial efficiency gains. Use of the sliding dichotomy allows sample sizes to be reduced by up to 40% without loss of statistical power. The proportional odds model gives modest additional gains over and above the gains achieved by use of the sliding dichotomy.
As with any simulation study, it is difficult to know how far the findings may be extrapolated beyond the actual situations that were modeled.
Both ordinal techniques offer substantial efficiency gains relative to the conventional binary analysis. The choice between the two techniques involves subtle value judgments. In the situations examined, the proportional odds model gave efficiency gains over and above the sliding dichotomy, but arguably, the sliding dichotomy is more intuitive and clinically appealing.
颅脑创伤的临床试验一直表现不佳，长期以来 III 期临床试验的结果均为“阴性”。导致这种结果的原因之一，很可能是常规分析方法效率低下，将有序结果量表二值化，从而丢弃了信息。
我们的目的是评估从有序结局数据中提取额外信息的技术（比例优势模型和滑动二分法）带来的潜在效率增益。此外，我们还评估了通过协变量调整可以获得的额外效率增益。
该研究基于模拟，模拟围绕从颅脑创伤的八项 III 期试验和三项观察性研究中提取的患者水平数据数据库构建。我们探讨了两种不同的假定治疗效果，一种符合比例优势模型，另一种假设干预的效果是降低死亡风险，而不改变幸存者的结局分布。结果以效率增益表示，以百分比形式报告，即与常规二值分析相比，在不降低统计效力的情况下，有序分析可减少的样本量。
模拟结果显示出显著的效率增益。使用滑动二分法可将样本量减少高达 40%，而不会损失统计效力。比例优势模型在使用滑动二分法获得的增益之外，还提供了适度的额外增益。
与任何模拟研究一样，很难知道研究结果在多大程度上可以外推到实际建模情况之外。
与传统的二值分析相比，两种有序技术都提供了显著的效率增益。在这两种技术之间的选择涉及微妙的价值判断。在所检查的情况下，比例优势模型在滑动二分法之外提供了效率增益，但可以说，滑动二分法更直观且更符合临床需求。
