Improved Patient Reported Outcomes (iPRO) -Sleep Diary: A Tool to Improve Sleep Assessment in Clinical Trials

摘要 失眠是一种非常普遍的疾病，严重降低了数百万人的生活质量和健康。 患者根据诊断定义，失眠是一种以自我报告的主观标准为特征的疾病， 针对失眠症的治疗开发人员通常根据患者报告评估其治疗效果 睡眠日记的形式。这种评估方法的一个关键缺陷是， 由于患者不能感知到无意识睡眠的过渡和从无意识睡眠的过渡 以及与偏见、情绪和其他背景因素相关的可变性来源。为了克服这一限制，许多 临床试验将临床验证的可穿戴设备作为替代评估纳入其试验中， 结合睡眠日记数据进行解释。可穿戴设备也是评估睡眠的不完美工具 因为它们同样受到非疾病、非治疗相关因素的限制，包括不完善的操作， 不完善的算法和滥用。此外，在临床和非临床人群中进行的许多研究 研究表明，睡眠日记和可穿戴设备产生的睡眠之间存在显着差异， 度量标准提出了一个问题，即哪种评估方法是有效的。如果没有一种方法来调和分歧 在睡眠日记和可穿戴设备之间，临床试验的当前实践是依赖于睡眠日记数据， 这是次优的并且可能导致试验中的钝化或不显著的效果。改善的病人 报告结果（iPRO）-睡眠日记是一种旨在通过以下方式改善睡眠评估的方法和系统： 结合睡眠日记和可穿戴设备数据，同时保持睡眠评估的主观性。的 所提出的解决方案是向患者提供他们的可穿戴设备导出的睡眠数据， 完成睡眠日记。患者报告的睡眠日记测量仍然是关注的结局， 不过，病人可自由决定在评估时是否采纳客观数据。这 该方法受到信号处理理论的启发，其中来自两个不相关的传感器的测量结果 结合误差源（睡眠日记和可穿戴设备），以改善对基础睡眠的测量。 信号了向患者提供他们的客观数据，然后使用他们的睡眠日记反应的方法（在 与平均值相反）用于保持患者自主性并利用自我报告数据的益处。 初步数据表明，iPRO-Sleep Diary非线性地提高了睡眠指标的测量精度 并且减少了设备和睡眠日记数据之间的差异。这一平台技术有望得到改善 在临床试验中评估睡眠，并能够更有效地开发有效的治疗方法。

Abstract Insomnia is a highly prevalent condition that significantly degrades the quality of life and health of millions of patients. By diagnostic definition, insomnia is a disease characterized by self-reported subjective criteria, thus therapeutic developers targeting insomnia typically evaluate their treatment’s efficacy based on patient reported outcomes in the form of sleep diaries. A critical flaw with this assessment approach is that self-perception of sleep is inherently noisy due to the inability of patients to perceive the transition to and from unconscious sleep and sources of variability related to bias, mood, and other contextual factors. To overcome this limitation, many clinical trials incorporate clinically validated wearable devices into their trials as surrogate assessments which are interpreted in conjunction with sleep diary data. Wearable devices are also imperfect tools to assess sleep because they are similarly limited by non-disease, non-treatment related factors including imperfect operation, imperfect algorithms, and misuse. Furthermore, numerous studies in clinical and non-clinical populations have demonstrated that there are significant discrepancies between sleep diaries and wearable device derived sleep metrics raising the question as to which assessment approach is valid. Without a method to reconcile differences between sleep diaries and wearable devices the current practice for clinical trials is to rely on sleep diary data which is suboptimal and may contribute to blunted or nonsignificant effects in trials. The improved patient reported outcome (iPRO) – Sleep Diary is a method and system designed to improve sleep assessment by combining sleep diary and wearable device data while maintaining the subjectivity of sleep assessment. The proposed solution is to provide patients their wearable device-derived sleep data contemporaneously with the completion of the sleep diary. The patient reported sleep diary measurement is still the outcome of interest, however patients have the freedom to incorporate or disregard their objective data in their assessment. This approach is inspired by signal processing theory where measurements from two sensors with uncorrelated sources of error (sleep diary and wearable device) are combined to improve the measurement of the underlying signal. The approach of providing patients their objective data and then using their sleep diary response (in contrast to averaging) is used to preserve patient autonomy and leverage the benefits of self-reported data. Preliminary data suggest the iPRO-Sleep Diary non-linearly improves measurement precision of sleep metrics and reduces discrepancy between device and sleep diary data. This platform technology is expected to improve the assessment of sleep in clinical trials and enable more efficient development of effective therapeutics.