Fecal Incontinence Treatment Study (FIT Study)

摘要 这是针对PAR-15-067的U 01初始申请。这一计划的宣布源于一个 2013年举办了NIDDK研讨会，以确定促进大便失禁（FI）研究的途径。 与会者确定了知识差距和取得进展的最佳方法， 生物反馈（BIO）、骶神经刺激（SNS）和肛周填充剂注射（INJ） 空间作为对照试验支持的治疗方法，但没有明确的迹象表明哪一种是最有效的， 最安全，最便宜。结果的测量是可变的，入选标准也不同。的 建议使用相同的范例比较所有3个。目的：（1）比较所有3种治疗方法， 疗效、安全性和成本的基础，以及次要结局指标。(2)识别生理的，临床的， 以及对每种治疗有反应的社会心理学预测因素。(3)允许对治疗无反应的患者 随机分配的治疗，以在3个月时选择第二次治疗。(4)比较治疗 看哪种组合看起来最好（不受控制）。(5)评估加强医疗服务的效果 有效性、安全性和成本管理（MM）（非受控）。(6)比较BIO的成本效益， 两年来，为FI提供SNS和INJ。方法：选择适合各种治疗方法的567例患者 包括每周>2次固体或液体FI。治疗应答者是指FI减少>75%的人 频率.主要评估是随机化治疗开始后3个月。如果患者 响应者，他们将继续研究24个月，但如果他们没有回应，他们将被提供 替代治疗和后续。次要结局包括缓解率， FI、BMI、布里斯托粪便严重程度量表、FI生活质量和经验证的严重程度量表（FI）的变化 严重程度量表，St. Mark’s FI严重程度量表）。心理结果包括PROMIS焦虑-7， 抑郁-8和自我效能量表。成本效益分析将基于质量调整寿命 年主持人将包括（1）生理评估（肛门超声，肛门直肠运动，和磁 诱发电位）;（2）治疗的先验信念（可信度/期望问卷），生活质量 （一般和FI特异性）、性别和FI类型（被动、冲动）。4名临床试验机构主要研究者（PI）为 Adil Bharucha（马约诊所）、Satish Rao（格鲁吉亚奥古斯塔大学）、Ann Lowry（结肠和直肠 明尼阿波利斯外科）和威廉怀特黑德（查佩尔山，北卡罗来纳州）-所有高级PI。数据的PI 协调中心（DCC）是玛丽·帕兹，也是一名经验丰富的PI。这是一个合作协议， NIDDK和弗兰克汉密尔顿将参与项目管理。一个成功的结果将引导 治疗算法和报销政策。

ABSTRACT This is an initial application for a U01 in response to PAR-15-067. This program announcement grew out of an NIDDK Workshop held in 2013 to identify pathways for promoting research on fecal incontinence (FI). Conference attendees identified gaps in knowledge and the best approaches to progress, and all identified Biofeedback (BIO), Sacral Neural Stimulation (SNS), and Injections of bulking agents (INJ) in the perianal space as treatments supported by controlled trials, but with no clear indication of which is most effective, safest, and least costly. Outcome measures have been variable, and inclusion criteria have also differed. The recommendation was to compare all 3 using the same paradigm. Aims: (1) Compare all 3 treatments on the basis of efficacy, safety, and cost, as well as secondary outcome measures. (2) Identify physiological, clinical, and psychosocial predictors of who will respond to each treatment. (3) Allow patients who do not respond to the randomly assigned treatment to select a second treatment at 3 months. (4) Compare treatment combinations to see which appears best (uncontrolled). (5) Assess the effects of enhanced Medical Management (MM) on efficacy, safety, and cost (uncontrolled). (6) Compare the cost-effectiveness of BIO, SNS, and INJ for FI throughout the two years. Methods: Select 567 patients appropriate to all treatments including >2 per week solid or liquid FI. A treatment responder is someone with >75% reduction in FI frequency. Primary assessment is 3 months after the beginning of randomized treatment. If patients are responders, they will continue to be studied for 24 months, but if they fail to respond they will be offered alternative treatment and followed. Secondary outcomes include the rate of responding with a 50% decrease in FI, continence, changes on the Bristol Stool Severity scale, FI Quality of Life, and validated severity scales (FI Severity Scale, St. Mark’s FI Severity Scale). Psychological outcomes include the PROMIS Anxiety-7, Depression-8, and Self-Efficacy scales. Costs effectiveness analysis will be based on Quality Adjusted Life Years. Moderators will include (1) physiological assessments (anal ultrasound, anorectal motility, and magnetic evoked potentials); (2) a priori beliefs in treatments (Credibility/Expectancy Questionnaire), quality of life (general and FI specific), sex, and type of FI (passive, urge). The 4 clinical site principal investigators (PIs) are Adil Bharucha (Mayo Clinic), Satish Rao (University of Augusta in Georgia), Ann Lowry (Colon and Rectal Surgery in Minneapolis), and William Whitehead (Chapel Hill, NC) – all senior PIs. The PI of the data coordinating center (DCC) is Marie Gantz, also an experienced PI. This is a collaborative agreement with NIDDK, and Frank Hamilton will participate in program management. A successful outcome will guide treatment algorithms and reimbursement policies.