Fecal Incontinence Treatment Study (FIT Study)

摘要 这是响应PAR-15-067的U01的初始申请。此计划公告源于一项 2013年举办了NIDDK研讨会，以确定促进大便失禁(FI)研究的途径。 与会者确定了知识方面的差距和取得进展的最佳方法，并确定了 生物反馈(BIO)、坐骨神经刺激(SNS)和肛周注射扩张剂(INJ) 太空治疗得到了对照试验的支持，但没有明确的迹象表明哪种治疗最有效， 最安全，最便宜。结果衡量标准是可变的，纳入标准也不同。这个 建议使用相同的范式来比较所有三种方法。目的：(1)比较三种处理方法的效果。 有效性、安全性和成本的基础，以及次要结果衡量标准。(2)确定生理、临床、 以及心理社会预测者，预测谁会对每种治疗做出反应。(3)允许对药物无反应的患者 随机分配治疗，在3个月时选择第二个治疗。(4)比较待遇 组合以查看哪个显示得最好(不受控制)。(5)评估强化医疗的效果 管理(MM)的有效性、安全性和成本(不受控制)。(6)比较BIO的成本-效果， SNS，以及两年中FI的INJ。方法：选择适合所有治疗的567例患者 包括每周2次固体或液体FI。治疗应答者是FI减少75%的人 频率初步评估是在随机治疗开始后3个月。如果病人是 应答者，他们将继续接受24个月的研究，但如果他们没有回应，他们将被提供 可供选择的治疗方法和后续治疗。次要结果包括响应率下降50% FI、大便可控性、Bristol大便严重程度量表、FI生活质量和有效严重程度量表(FI 严重程度量表、圣马可FI严重程度量表)。心理结果包括Promis焦虑-7， 抑郁-8和自我效能感量表。成本效益分析将以质量调整寿命为基础 好多年了。主持人将包括(1)生理评估(肛门超声、肛门直肠动力和磁力 诱发电位)；(2)对治疗的先验信念(可信度/预期问卷)、生活质量 (一般和特定于FI)、性别和FI类型(被动、冲动)。4个临床现场首席调查员(PI)是 Adil Bharucha(梅奥诊所)、Satih Rao(格鲁吉亚奥古斯塔大学)、Ann Lowry(结肠和直肠 明尼阿波利斯的外科手术)和威廉·怀特黑德(北卡罗来纳州教堂山)--都是高级PI。数据的PI 协调中心(DCC)是玛丽·甘茨，也是一位经验丰富的PI。这是一项与 NIDDK和Frank Hamilton将参与项目管理。一个成功的结果将指导 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.