Geriatric Psychiatry, Columbia University Irving Medical Center, New York, New York, USA
Biostatistics, Columbia University Medical Center, New York, New York, USA.
J Neurol Neurosurg Psychiatry. 2023 Dec 14;95(1):2-7. doi: 10.1136/jnnp-2023-331941.
Per cent slowing of decline is frequently used as a metric of outcome in Alzheimer's disease (AD) clinical trials, but it may be misleading. Our objective was to determine whether per cent slowing of decline or Cohen's d is the more valid and informative measure of efficacy.
Outcome measures of interest were per cent slowing of decline; Cohen's d effect size and number-needed-to-treat (NNT). Data from a graphic were used to model the inter-relationships among Cohen's d, placebo decline in raw score units and per cent slowing of decline with active treatment. NNTs were computed based on different magnitudes of d. Last, we tabulated recent AD anti-amyloid clinical trials that reported per cent slowing and for which we computed their respective d's and NNTs.
We demonstrated that d and per cent slowing were potentially independent. While per cent slowing of decline was dependent on placebo decline and did not include variance in its computation, d was dependent on both group mean difference and pooled SD. We next showed that d was a critical determinant of NNT, such that NNT was uniformly smaller when d was larger. In recent AD associated trials including those focused on anti-amyloid biologics, d's were below 0.23 and thus considered small, while per cent slowing was in the 22-29% range and NNTs ranged from 14 to 18.
Standardised effect size is a more meaningful outcome than per cent slowing of decline because it determines group overlap, which can directly influence NNT computations, and yield information on the likelihood of minimum clinically important differences. In AD, greater use of effect sizes, NNTs, rather than relative per cent slowing, will improve the ability to interpret clinical trial results and evaluate the clinical meaningfulness of statistically significant results.
在阿尔茨海默病（AD）临床试验中，衰退的百分比减缓经常被用作结果的衡量标准，但它可能具有误导性。我们的目的是确定衰退的百分比减缓或 Cohen's d 哪个是更有效和信息量更大的疗效衡量标准。
感兴趣的结果测量指标包括衰退的百分比减缓；Cohen's d 效应大小和需要治疗的人数（NNT）。使用图形中的数据来模拟 Cohen's d、安慰剂在原始分数单位中的下降以及与活性治疗相关的衰退百分比减缓之间的相互关系。NNT 是基于不同大小的 d 计算的。最后，我们列出了最近报告衰退百分比减缓的 AD 抗淀粉样蛋白临床试验，并计算了它们各自的 d 值和 NNT 值。
我们证明了 d 和衰退的百分比减缓可能是独立的。虽然衰退的百分比减缓取决于安慰剂的下降，并且在其计算中不包括方差，但 d 取决于组平均差异和合并 SD。我们接下来表明，d 是 NNT 的关键决定因素，因此当 d 较大时，NNT 会均匀减小。在最近的 AD 相关临床试验中，包括那些专注于抗淀粉样蛋白生物制剂的试验，d 值低于 0.23，因此被认为是较小的，而衰退的百分比减缓在 22-29%的范围内，NNT 值范围从 14 到 18。
标准化效应大小是比衰退的百分比减缓更有意义的结果，因为它确定了组重叠，这可以直接影响 NNT 的计算，并提供关于最小临床重要差异的可能性的信息。在 AD 中，更多地使用效应大小、NNT，而不是相对衰退的百分比减缓，将提高解释临床试验结果和评估统计学显著结果的临床意义的能力。
