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介行为减肥计划，以帮助肥胖成年人实现具有临床意义的体重减轻8-10%的起始体重。然而，观察到反应异质性，一半的参与者无法实现这一目标。尽管存在这种异质性，但“一刀切”的做法是常态，这是一个主要缺点，因为实际上可以及早发现无反应。减肥干预科学的这一差距需要一种适应性干预方法，这种方法可以“在正确的时间为正确的人提供正确的治疗”。适应性干预措施通过医学支持的决策规则来个性化治疗，这些规则建议治疗应在何时以及如何随着时间的推移展开，以最大限度地提高疗效。序贯多重分配随机试验（SMART）是为了建立最佳适应性干预措施而明确开发的，它使用实验设计原则来制定这些决策规则。此应用程序是响应“PA-13-165：创新的研究方法：预防和管理慢性疾病的症状”，是我们所知道的第一个将这种创新的方法论方法应用于成人减肥。我们提出了一个SMART系统地评估治疗方法和时间的变化与无应答者进行干预。改变治疗策略的决定应该考虑到人们减肥的原因。自我监管的挑战已被确定为一个主要的遵守障碍。解决自我调节困难的两个有吸引力的选择是：1）通过膳食替代品（MR）增加行为治疗，减少自我调节的需要; 2）通过教授接受和承诺技能（ACT）来改变治疗方法，提高自我调节能力。此外，将评价干预无应答者的两个时间点：1）5周，基于新出现的体重减轻试验证据; 2）10周，基于现有阶梯式护理文献中使用的平均持续时间。将招募30 kg/m2 d BMI d 45 kg/m2的成人（n=500），并接受个体行为减肥治疗（BWL）。受试者将被随机分配至：1）第5周的治疗反应评估或2）第10周的治疗反应评估。在第5周和第10周被确定为无应答者的受试者将被重新随机分配至“补充膳食”或“转换为ACT”。被确定为应答者的参与者继续接受BWL治疗。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个月时进行。主要目的是评价MR增强治疗与转换为ACT治疗无应答者的获益。第二个目的是评估对无应答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，这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.