London, ON, Canada.
Calgary, AB, Canada.
Aliment Pharmacol Ther. 2021 May;53(10):1108-1117. doi: 10.1111/apt.16328. Epub 2021 Mar 18.
Pouchitis is a condition with large unmet medical needs and no approved therapies. Lack of validated instruments to measure disease activity and treatment response is a major barrier to drug development.
To conduct a modified RAND/University of California Los Angeles appropriateness process to produce a standardised assessment of pouchitis disease activity in clinical trials.
A list of 164 items generated upon a systematic review and expert opinion were rated based on a 9-point scale (appropriate, uncertain and inappropriate), by a panel including 16 gastroenterologists, surgeons and histopathologists.
Items rated as appropriate to evaluate in pouchitis clinical trials were: (a) clinical: stool frequency and faecal urgency; (b) endoscopic: primary assessment in the pouch body according to the percentage of affected area (<50%, 50%-75% and >75%), evaluation of the presence of ulcers/erosions according to size (erosions <5 mm, ulcers ≥5 mm to 2 cm and large ulcers >2 cm) and ulcerated area (<10%, 10%-30% and >30%); (c) histologic: two biopsies from each segment, from the ulcer's edge when present, or endoscopically normal areas, assessment of lamina propria chronic inflammation, epithelial and lamina propria neutrophils, epithelial damage, erosions and ulcers; and (d) clinical trial inclusion/outcome criteria: minimum histologic disease activity for inclusion, a primary endpoint based on stool frequency and assessment of clinical, endoscopic and histologic response and remission. The overall majority of items surveyed (100/164) were rated 'uncertain'.
We conducted a RAND/UCLA appropriateness process to help inform measurement of pouchitis disease activity within clinical trials and foster the development of novel therapies.
pouchitis 是一种存在大量未满足医疗需求且尚无获批疗法的疾病。缺乏用于衡量疾病活动度和治疗反应的经过验证的工具，是药物研发的主要障碍。
通过改良的 RAND/加州大学洛杉矶分校适宜性程序，制定 pouchitis 疾病活动度的标准化评估标准，以用于临床试验。
通过系统回顾和专家意见生成了 164 项条目清单，由包括 16 名胃肠病学家、外科医生和组织病理学家在内的专家组，对这些条目按照 9 分制（适宜、不确定和不适宜）进行评分。
评估 pouchitis 临床试验中适宜评估的条目为：（a）临床：粪便频率和粪便急迫感；（b）内镜：根据受影响面积的百分比（<50%、50%-75%和>75%）评估 pouch 体的初步情况，根据大小评估溃疡/糜烂的存在情况（糜烂<5mm、溃疡≥5mm 至 2cm 和大溃疡>2cm）和溃疡面积（<10%、10%-30%和>30%）；（c）组织学：每段取两块活检，当存在溃疡时取自溃疡边缘，或取自内镜正常部位，评估固有层慢性炎症、上皮和固有层中性粒细胞、上皮损伤、糜烂和溃疡；（d）临床试验纳入/结局标准：纳入的最低组织学疾病活动度，基于粪便频率的主要终点，以及临床、内镜和组织学反应和缓解的评估。调查的绝大多数条目（100/164）被评为“不确定”。
我们进行了 RAND/UCLA 适宜性程序，以帮助告知临床试验中 pouchitis 疾病活动度的测量，并促进新型疗法的开发。
