Evaluating Options for Non-Responders: A SMART Approach to Enhancing Weight Loss

描述（由申请人提供）：美国预防服务工作组建议转诊到行为减肥计划，以帮助肥胖成年人实现有临床意义的体重减轻8-10%的起始体重。然而，有一半的参与者无法达到这一目标，观察到反应异质性。尽管存在这种异质性，但“一刀切”的方法是标准的，这是一个主要的缺点，因为实际上可以在早期检测到无响应。减肥干预科学的这一空白要求一种适应性干预方法，可以提供“在正确的时间为正确的人提供正确的治疗”。适应性干预通过经验支持的决策规则来个性化治疗，建议何时以及如何随着时间的推移展开治疗，以最大限度地提高效果。序贯多任务随机试验（SMART），明确地建立最优的适应性干预，使用实验设计原则来制定这些决策规则。该应用程序响应“PA-13-165：创新研究方法：慢性疾病症状的预防和管理”，是我们所知道的第一个将这种创新的方法方法应用于成人减肥。我们提出了一个SMART来系统地评估治疗方法和无反应干预的时间变化。改变治疗策略的决定应该考虑到人们努力减肥的原因。自我调节的挑战已被确定为主要的依从性障碍。解决自我调节困难的两个有吸引力的选择是：1)增加代餐（MR）的行为治疗，减少自我调节的需要；2)通过教授提高自我调节能力的接受和承诺技能（ACT）来转换治疗方法。此外，将评估干预无应答者的两个时间点：1)5周，基于新出现的减肥试验证据；2) 10周，基于现有阶梯护理文献中使用的平均持续时间。招募体重指数为30 kg/m2和45 kg/m2的成年人（n=500），接受个体行为减肥治疗（BWL）。参与者将被随机分配到：1)治疗反应评估在5周或2)治疗反应评估在10周。在第5周和第10周被确定为无反应的参与者将被重新随机分配到：“增加代餐”或“切换到ACT”。被确定为应答者的参与者继续进行BWL。所有参与者接受6个月的干预；研究评估在基线、6个月和18个月进行。主要目的是评估强化MR治疗与对无反应者改用ACT治疗的益处。第二个目的是评估对无反应者进行干预的最佳时间。这些SMART结果将导致经验支持的个性化适应性干预的构建，该干预将优化肥胖成年人的减肥结果和相关的健康益处。

DESCRIPTION (provided by applicant): The US Preventive Services Task Force recommends referral to behavioral weight loss programs to help obese adults achieve a clinically meaningful weight loss of 8-10% of starting body weight. However, response heterogeneity is observed with half of participants unable to achieve this goal. Despite this heterogeneity, a "one size fits all" approach is the norm, a major drawback because non-response can in fact be detected early. This gap in weight loss intervention science calls for an adaptive intervention approach that could provide the "right treatment at the right time for the right person". Adaptive interventions individualize treatment through empirically-supported decision rules advising when and how treatments should unfold over time to maximize effectiveness. Sequential Multiple Assignment Randomized Trials (SMART), developed explicitly to build optimal adaptive interventions, use experimental design principles to develop these decision rules. This application is responsive to "PA-13-165: Innovative Research Methods: Prevention and Management of Symptoms in Chronic Illness" and is the first we are aware of to apply this innovative methodological approach to adult weight loss. We propose a SMART to systematically evaluate therapeutic approach and timing variations for intervening with non-responders. Decisions about altering therapeutic strategy should take into consideration the reasons people struggle with weight loss. Self-regulation challenges have been identified as a major adherence barrier. Two attractive options to address self-regulation difficulties are: 1) augmenting behavioral treatment with Meal Replacements (MR) which decreases the need for self-regulation; and 2) switching therapeutic approaches by teaching acceptance and commitment skills (ACT) which boost capacity for self-regulation. Additionally, two time points for intervening with non-responders will be evaluated: 1) 5 weeks, based on emerging weight loss trial evidence; and 2) 10 weeks, based on average duration used in the extant stepped care literature. Adults (n=500) with 30 kg/m2 d BMI d 45 kg/m2 will be recruited and will receive individual behavioral weight loss treatment (BWL). Participants will be randomized to either: 1) treatment response assessment at 5 weeks or 2) treatment response assessment at 10 weeks. Participants identified as non-responders at Week 5 and Week 10 will be re-randomized to either: "Augment with Meal Replacements" or "Switch to ACT". Participants identified as responders continue with BWL. All participants receive 6 months of intervention; research assessments take place at baseline, 6- and 18-months. The primary aim is to evaluate the benefit of augmenting treatment with MR's versus switching to ACT for non-responders. The secondary aim is to evaluate the optimal time to intervene with non-responders. These SMART results will lead to the empirically supported construction of an individualized adaptive intervention that will optimize weight loss outcomes and associated health benefits for obese adults.