Rapp Paul E, Cellucci Christopher J, Keyser David O, Gilpin Adele M K, Darmon David M
Department of Military and Emergency Medicine, Uniformed Services University , Bethesda, MD , USA.
Front Neurol. 2013 Nov 19;4:177. doi: 10.3389/fneur.2013.00177.
The identification and longitudinal assessment of traumatic brain injury presents several challenges. Because these injuries can have subtle effects, efforts to find quantitative physiological measures that can be used to characterize traumatic brain injury are receiving increased attention. The results of this research must be considered with care. Six reasons for cautious assessment are outlined in this paper. None of the issues raised here are new. They are standard elements in the technical literature that describes the mathematical analysis of clinical data. The purpose of this paper is to draw attention to these issues because they need to be considered when clinicians evaluate the usefulness of this research. In some instances these points are demonstrated by simulation studies of diagnostic processes. We take as an additional objective the explicit presentation of the mathematical methods used to reach these conclusions. This material is in the appendices. The following points are made: (1) A statistically significant separation of a clinical population from a control population does not ensure a successful diagnostic procedure. (2) Adding more variables to a diagnostic discrimination can, in some instances, actually reduce classification accuracy. (3) A high sensitivity and specificity in a TBI versus control population classification does not ensure diagnostic successes when the method is applied in a more general neuropsychiatric population. (4) Evaluation of treatment effectiveness must recognize that high variability is a pronounced characteristic of an injured central nervous system and that results can be confounded by either disease progression or spontaneous recovery. A large pre-treatment versus post-treatment effect size does not, of itself, establish a successful treatment. (5) A procedure for discriminating between treatment responders and non-responders requires, minimally, a two phase investigation. This procedure must include a mechanism to discriminate between treatment responders, placebo responders, and spontaneous recovery. (6) A search for prodromes of neuropsychiatric disorders following traumatic brain injury can be implemented with these procedures.
创伤性脑损伤的识别和纵向评估存在若干挑战。由于这些损伤可能具有细微影响，寻找可用于表征创伤性脑损伤的定量生理指标的工作正受到越来越多的关注。必须谨慎考虑这项研究的结果。本文概述了六个需要谨慎评估的原因。这里提出的问题都不是新问题。它们是描述临床数据数学分析的技术文献中的标准要素。本文的目的是提请注意这些问题，因为临床医生在评估这项研究的实用性时需要考虑这些问题。在某些情况下，这些要点通过诊断过程的模拟研究得到了证明。我们的另一个目标是明确呈现用于得出这些结论的数学方法。这些内容在附录中。提出了以下几点：（1）临床人群与对照人群在统计学上有显著差异并不能确保诊断程序成功。（2）在诊断判别中添加更多变量，在某些情况下，实际上可能会降低分类准确性。（3）在创伤性脑损伤与对照人群分类中具有高敏感性和特异性，当该方法应用于更广泛的神经精神疾病人群时，并不能确保诊断成功。（4）治疗效果评估必须认识到高变异性是受伤中枢神经系统的一个显著特征，并且结果可能会因疾病进展或自发恢复而混淆。治疗前与治疗后的大效应量本身并不能确立成功的治疗。（5）区分治疗反应者和无反应者的程序至少需要两阶段调查。该程序必须包括一种区分治疗反应者、安慰剂反应者和自发恢复的机制。（6）可以通过这些程序来寻找创伤性脑损伤后神经精神疾病的前驱症状。
