Melbourne School of Health Sciences, University of Melbourne, Heidelberg, Australia.
Melbourne Medical School, University of Melbourne, Parkville, Australia.
Ann Phys Rehabil Med. 2022 Jan;65(1):101487. doi: 10.1016/j.rehab.2021.101487. Epub 2021 Nov 23.
To enable development of effective interventions, there is a need to complete systematic early-phase dose articulation research. This scoping review aimed to synthesize dose articulation research of behavioral motor interventions for stroke recovery.
MEDLINE and EMBASE were systematically searched for dose articulation studies. Preclinical experiments and adult clinical trials were classified based on the discovery pipeline and analyzed to determine which dose dimensions were articulated (time, scheduling or intensity) and how they were investigated (unidimensional vs multidimensional approach). Reporting of dose, safety and efficacy outcomes were summarized. The intervention description, risk of bias, and quality was appraised.
We included 41 studies: 3 of preclinical dose preparation (93 rodents), 2 Phase I dose ranging (21 participants), 9 Phase IIA dose screening (198 participants), and 27 Phase IIB dose finding (1879 participants). All studies adopted a unidimensional approach. Time was the most frequent dimension investigated (53%), followed by intensity (29%), and scheduling (18%). Overall, 95% studies reported an efficacy outcome; however, only 65% reported dose and 45% reported safety. Across studies, 61% were at high risk of bias, and the average percentage reporting of intervention description and quality was 61% and 67%, respectively.
This review highlights a need to undertake more high-quality, early-phase studies that systematically articulate intervention doses from a multidimensional perspective in the field of behavioral motor stroke recovery. To address this gap, we need to invest in adapting early phase trial designs, especially Phase I, to support multidimensional dose articulation.
为了开发有效的干预措施，需要完成系统的早期剂量制定研究。本范围综述旨在综合行为运动干预中风康复的剂量制定研究。
系统地检索了 MEDLINE 和 EMBASE 中的剂量制定研究。根据发现管道对临床前实验和成人临床试验进行分类，并进行分析，以确定哪些剂量维度得到了阐述（时间、安排或强度）以及如何进行研究（单维方法与多维方法）。总结了剂量、安全性和疗效结果的报告。评估了干预描述、偏倚风险和质量。
我们纳入了 41 项研究：3 项临床前剂量准备（93 只啮齿动物），2 项 1 期剂量范围研究（21 名参与者），9 项 2A 期剂量筛选研究（198 名参与者），和 27 项 2B 期剂量发现研究（1879 名参与者）。所有研究均采用单维方法。时间是最常研究的维度（53%），其次是强度（29%）和安排（18%）。总体而言，95%的研究报告了疗效结果；然而，只有 65%的研究报告了剂量，45%的研究报告了安全性。在研究中，61%的研究存在高偏倚风险，分别有 61%和 67%的研究报告了干预描述和质量。
本综述强调需要开展更多高质量的早期阶段研究，从行为运动中风康复领域的多维角度系统地阐述干预剂量。为了解决这一差距，我们需要投资于早期阶段试验设计的调整，特别是 1 期试验设计，以支持多维剂量制定。
