评估脊柱治疗生物标志物试验的设计与原理：一项序贯多重分配随机试验

The design and rationale of the Biomarkers for Evaluating Spine Treatments trial: a sequential multiple assignment randomized trial.

作者信息

Mauck Matthew C, Barth Kelly S, Bell Kevin M, Brooks Amber K, Chadwick Andrea L, Gunn Cameron A, Hurley Robert W, Ivanova Anastasia, Piva Sara R, Schneider Michael J, Bailey Jeannie F, Bagaason Sarah, Batorsky Anna, Borckardt Jeffrey J, Bowden Anton E, Carey Timothy S, Castellanos Joel, Chen Lucy, Chidgey Brooke, Dalton Diane, Dufour Jonathan S, Fields Aaron J, Fritz Julie M, Goolsby Rachel West, Greco Carol M, Harris Richard E, Harte Steven, Hassett Afton L, Hoffmeyer Anna, Jones Berkeley Sara, Kaplan Chelsea, Kidwell Kelley M, Knapik Gregory G, Kosorok Michael R, Kurillo Gregorij, Lobo Remy, Lotz Jeffrey C, Mackey Sean, Mageswaran Prasath, Majumdar Sharmila, Mao Jianren, Marras William S, McCumber Micah, McLean Samuel A, Mehling Wolf, Mitchell Ulrike H, Napadow Vitaly J, O'Neill Conor, Patel Kushang V, Peltier Scott, Psioda Matthew, Rowland Bryce, Rundell Sean D, Schrepf Andrew, Sperger John, Vo Nam, Wallace Mark S, Wasan Ajay D, Weaver Tristan E, Weber Kenneth A, Williams David A, Wilson Leslie, Zeidan Fadel, Zhao Beibo, Anstrom Kevin J, Clauw Daniel J, Sowa Gwendolyn A

机构信息

Department of Anesthesiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, United States.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, United States.

出版信息

Pain Med. 2025 Sep 1;26(9):538-553. doi: 10.1093/pm/pnaf032.

DOI:10.1093/pm/pnaf032

PMID:40205455

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12405758/

Abstract

OBJECTIVE

Chronic low back pain (cLBP) is a common condition that impacts quality of life and function. There are many evidence-based treatments to address cLBP; however, treatment effects are modest, perhaps in part due to individual variation in treatment response. The Biomarkers for Evaluating Spine Treatments (BEST) trial was designed as the collaborative centerpiece of the Back Pain Consortium (BACPAC) research program. This consortium was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) as part of the Helping to End Addiction Long-term (HEAL) Initiative.

DESIGN

The BEST trial was a sequential multiple assignment randomized trial (SMART) designed with the primary goal of identifying in whom different treatments show optimal response. The primary focus of the study was to use patient features, including biomarkers and phenotypic measures, to identify subsets of persons with cLBP who respond best to specific common treatments.

METHODS

Four interventions were chosen for the trial: Enhanced Self-Care, Acceptance and Commitment Therapy, Duloxetine, and Evidence-Based Exercise and Manual Therapy. Following a run-in period and baseline assessment, participants were randomized to 1 of the 4 treatments for the first 12-week intervention period. Participants were reassessed and based on their self-reported response to initial treatment, continued that initial treatment, were augmented with an additional randomly assigned treatment, or were switched to a new treatment.

CONCLUSION

This trial was designed to deliver rich phenotypic data that will both potentially aid in the discovery of phenotypic characteristics that predict treatment response and provide a greater mechanistic understanding of cLBP.

CLINICAL TRIAL REGISTRATION NUMBER

The Biomarkers for Evaluating Spine Treatments (BEST) trial is registered on ClinicalTrials.gov (Registration number: NCT05396014; https://clinicaltrials.gov/study/NCT05396014).

摘要

目的

慢性下腰痛（cLBP）是一种影响生活质量和功能的常见病症。有许多基于证据的治疗方法可用于治疗cLBP；然而，治疗效果一般，这可能部分归因于个体对治疗反应的差异。评估脊柱治疗的生物标志物（BEST）试验被设计为背痛联盟（BACPAC）研究项目的协作核心。该联盟由美国国立关节炎、肌肉骨骼和皮肤病研究所（NIAMS）赞助，是帮助终结长期成瘾（HEAL）倡议的一部分。

设计

BEST试验是一项序贯多重分配随机试验（SMART），其主要目标是确定不同治疗方法对哪些人显示出最佳反应。该研究的主要重点是利用患者特征，包括生物标志物和表型测量，来识别对特定常见治疗反应最佳的cLBP患者亚组。

方法

试验选择了四种干预措施：强化自我护理、接受与承诺疗法、度洛西汀以及基于证据的运动和手法治疗。在经过导入期和基线评估后，参与者在第一个12周的干预期被随机分配到四种治疗方法中的一种。对参与者进行重新评估，并根据他们对初始治疗的自我报告反应，继续接受初始治疗，增加一种额外随机分配的治疗方法，或者改用新的治疗方法。