N-of-1 Trials Using mHealth in Chronic Pain

慢性肌肉骨骼疼痛（MSP）是一个巨大的问题，影响超过1亿美国人（许多来自弱势群体），成本高达1600亿美元。目前的药物治疗策略传达了利益和风险的混合。在通常的实践中，临床医生往往不情愿地求助于阿片类镇痛药， 当其他药物似乎无效或禁忌时。找到一个有效的方案往往是一个试验和错误的问题。这种方法可能有效，但会产生偏见。一种在短期内看起来有效（或无效）的治疗方法可能只是因为患者基础状况的随机波动而显得如此。为了发现真正的效果，从而优化个体治疗，需要更科学的方法。N-of-1试验是在单个患者中进行的随机对照交叉试验。通过多次在两种治疗之间来回交叉患者，临床医生可以比普通实践中更精确地确定对该个体患者更有效的方法。通过产生个体治疗效果，n-of-1试验对"循证试验和错误"提出了挑战，"循证试验和错误"是治疗慢性症状性疾病的主导临床范式。N-of-1试验是一种直观吸引人且明显成功的方法，但未能获得太多牵引力，主要原因是缺乏基础设施。移动的设备可以改变这一点。该提案将移动的技术与个性化医疗保健结合起来，以解决确定什么对个体患者有效的临床问题。我们的目标是为患者及其临床医生提供识别个体治疗效果的工具，并从患者结局和医疗保健系统成本方面评估这种方法。该应用程序的具体目标是：1）开发和完善一个移动的Web应用程序（"Trialist"），以进行n-of 1项慢性肌肉骨骼疼痛脆弱患者试验; 2）在随机对照试验（RCT）中评估参与移动的n-of-1试验（与usul护理相比）对临床结局、参与性决策、满意度、依从性和医疗保健成本的影响。在Open www.example.com已经开发的软件架构的基础上，研究团队将在项目的前18个月内开发、完善和测试Trialist软件。然后，296例慢性肌肉骨骼疼痛患者将被随机分配使用Trialist进行n-1试验或常规治疗。主要假设是，与分配到常规护理的患者相比，分配到Trialist的患者将经历更好的长期结局（特别是6个月时的疼痛干扰）。实现这些目标将为更广泛地采用mHealth n-of-1试验治疗慢性疼痛奠定基础，并促进mHealth n-of-1试验在设计慢性医疗保健管理中的使用。

DESCRIPTION (provided by applicant): Chronic musculoskeletal pain (MSP) is an enormous problem, affecting more than 100 million Americans (many from disadvantaged groups) and costing upwards of $160 billion. Current pharmaco-therapeutic strategies convey a mix of benefits and hazards. In usual practice, clinicians resort to opioid analgesics, often reluctantly, when other drugs are seemingly ineffective or contraindicated. Finding an effective regimen is frequently a matter of trial and error. This approach may work but is subject to bias. A treatment that appears effective (or ineffective) over the short term may only seem so because of random fluctuation in the patient's underlying condition. To discover the true effect and thus optimize individual treatment, a more scientific approach is needed. N-of-1 trials are randomized controlled crossover trials conducted in a single patient. By crossing a patient back and forth between two treatments several times, clinicians can identify the more effective approach for that individual patient with greater precision than can be achieved in ordinary practice. By generating individual treatment effects, n-of-1 trials pose a challenge to "evidence-based trial and error," the reigning clinical paradigm for treatment of chronic, symptomatic conditions. N-of-1 trials are an intuitively appealing and demonstrably successful approach but have failed to gain much traction, largely due to lack of infrastructure. Mobile devices can change that. This proposal weds mobile technology with personalized health care to address the clinical problem of determining what works for an individual patient. Our goal is to provide tools for identifying individual treatment effects to patients and their clinicians, and to evaluate this approach in terms of patient outcomes and costs to the health care system. The specific aims of this application are: 1) to develop and refine a mobile web application ("the Trialist") to conduct n-of 1 trials among vulnerable patients with chronic musculoskeletal pain; and 2) to assess in a randomized controlled trial (RCT) the effects of participating in a mobile n-of-1 trial (versus usul care) on clinical outcomes; participatory decision making; satisfaction; adherence; and health care costs. Building on software architecture already developed by Open mHealth.org, the research team will develop, refine, and test the Trialist software over the first 18 months of the project. Then 296 patients with chronic musculoskeletal pain will be randomized to using Trialist to conduct an n-of-1 trial or to usual care. The main hypothesis is that patients assigned to the Trialist will experience better long term outcomes (particularly pain interference at 6 months) compared with those assigned to usual care. Achieving these aims will set the stage for broader uptake of mHealth n-of-1 trials in chronic pain and facilitate use of mHealth n-of-1 trials in designing chronic health care management.