Concerns Regarding the Standard Deviation of Individual Responses for Assessing Treatment Response Heterogeneity.

IF 3.3 3区 医学 Q1 PHYSIOLOGY
Aaron R Caldwell, David B Allison, Andrew W Brown, Gary L Gadbury, Thirupathi Reddy Mokalla, R Drew Sayer, Andrew D Vigotsky
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引用次数: 0

Abstract

The estimation of treatment response heterogeneity (TRH) is increasingly important as medicine moves toward personalized approaches. While various statistical methods have been proposed to quantify TRH in parallel-group trials, the standard deviation of individual responses (SDIR) has gained prominence within physiological research. This method is intended to quantify individual response variation by comparing standard deviations of change scores between intervention and control groups. We acknowledge that SDIR represents an improvement over many other flawed approaches that often involve responder counting. However, SDIR has critical limitations: 1) it cannot overcome the fundamental problem of causal inference because the correlation between potential outcomes remains unidentifiable, 2) it is incorrectly predicated on the assumption that TRH is present only when treatment group variance exceeds control group variance, and 3) it is statistically inefficient. We present an alternative framework, which involves assessing heteroskedasticity and estimating the bounds for the standard deviation of treatment effects (SDD). The presence of heteroskedasticity between treatment groups is a sufficient but not necessary condition for the presence of TRH. Further, SDD makes fewer assumptions than SDIR and, therefore, paints a more complete picture of potential TRH. Using data from a published exercise physiology study, we demonstrate how SDD can better characterize uncertainty in TRH estimation. We recommend researchers probe TRH by assessing heteroskedasticity, providing bounds for SDD, and estimating outcome distributions and probabilities while carefully crafting the theoretical rationale for the presence of TRH.

对评估治疗反应异质性的个体反应标准偏差的关注。
随着医学向个性化方向发展,治疗反应异质性(TRH)的评估变得越来越重要。虽然在平行组试验中提出了各种统计方法来量化TRH,但个体反应的标准偏差(SDIR)在生理学研究中得到了突出的地位。该方法旨在通过比较干预组和对照组之间变化评分的标准差来量化个体反应差异。我们承认SDIR代表了许多其他有缺陷的方法的改进,这些方法通常涉及应答者计数。然而,SDIR有严重的局限性:1)它不能克服因果推理的根本问题,因为潜在结果之间的相关性仍然无法确定;2)它错误地预测了TRH只有在治疗组方差超过对照组方差时才存在的假设;3)它在统计上效率低下。我们提出了另一种框架,包括评估异方差性和估计治疗效果标准偏差(SDD)的界限。治疗组间异方差的存在是TRH存在的充分条件,但不是必要条件。此外,SDD比SDIR做出的假设更少,因此可以描绘出更完整的潜在TRH图景。利用一项已发表的运动生理学研究的数据,我们证明了SDD如何更好地表征TRH估计中的不确定性。我们建议研究人员通过评估异方差、提供SDD的界限、估计结果分布和概率来探索TRH,同时仔细制定TRH存在的理论依据。
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来源期刊
CiteScore
6.00
自引率
9.10%
发文量
296
审稿时长
2-4 weeks
期刊介绍: The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.
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