PDF(Pubmed)
Abstract：
BACKGROUND: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.
OBJECTIVE: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.
METHODS: Representatives from various disciplines including urologists, oncologists, pathologists, statisticians, basic and translational scientists, and the patient advocacy community participated. The workshop format included invited lectures, panel discussions, and opportunity for audience discussion and comment.
RESULTS: In a pre-workshop survey, 92% of urologists surveyed considered the development of alternatives to BCG as a high drug development priority for BCG-naïve high-risk patients. Key topics discussed included definitions of disease states; trial design for BCG-naïve NMIBC, BCG-unresponsive carcinoma in situ, and BCG-unresponsive papillary carcinoma; strengths and limitations of single-arm trial designs; assessing patient-reported outcomes; and considerations for assessing avoidance of cystectomy as an efficacy measure.
CONCLUSIONS: The workshop discussed several important opportunities for trial design refinement in NMIBC. FDA encourages sponsors to meet with the appropriate review division to discuss trial design proposals for NMIBC early in drug development.
OBJECTIVE: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.
METHODS: Representatives from various disciplines including urologists, oncologists, pathologists, statisticians, basic and translational scientists, and the patient advocacy community participated. The workshop format included invited lectures, panel discussions, and opportunity for audience discussion and comment.
RESULTS: In a pre-workshop survey, 92% of urologists surveyed considered the development of alternatives to BCG as a high drug development priority for BCG-naïve high-risk patients. Key topics discussed included definitions of disease states; trial design for BCG-naïve NMIBC, BCG-unresponsive carcinoma in situ, and BCG-unresponsive papillary carcinoma; strengths and limitations of single-arm trial designs; assessing patient-reported outcomes; and considerations for assessing avoidance of cystectomy as an efficacy measure.
CONCLUSIONS: The workshop discussed several important opportunities for trial design refinement in NMIBC. FDA encourages sponsors to meet with the appropriate review division to discuss trial design proposals for NMIBC early in drug development.
摘要：
背景：尽管最近开发了非肌肉浸润性膀胱癌（NMIBC）的药物，很少有疗法被美国食品和药物管理局（FDA）批准，并且仍然存在未满足的临床需求。卡介苗（BCG）供应问题强调了为NMIBC开发安全有效药物的重要性。
目的：在2021年11月18日至19日，FDA举办了一个公共虚拟研讨会，讨论NMIBC的研究需求和潜在的试验设计，以便未来开发有效疗法。
方法：来自包括泌尿科医师在内的各个学科的代表，肿瘤学家,病理学家,统计学家,基础和翻译科学家，患者倡导社区参与。研讨会形式包括邀请讲座，小组讨论,以及观众讨论和评论的机会。
结果：在研讨会前的调查中，接受调查的92％的泌尿科医生认为，卡介苗替代品的开发是卡介苗的高风险患者的高药物开发优先事项。讨论的关键主题包括疾病状态的定义；卡介苗NMIBC的试验设计，卡介苗原位癌无反应，和BCG无反应的乳头状癌;单臂试验设计的优势和局限性;评估患者报告的结局;以及评估避免膀胱切除术作为疗效指标的考虑因素。
结论：研讨会讨论了在NMIBC中改进试验设计的几个重要机会。FDA鼓励赞助商在药物开发早期与适当的审查部门会面，讨论NMIBC的试验设计方案。
目的：在2021年11月18日至19日，FDA举办了一个公共虚拟研讨会，讨论NMIBC的研究需求和潜在的试验设计，以便未来开发有效疗法。
方法：来自包括泌尿科医师在内的各个学科的代表，肿瘤学家,病理学家,统计学家,基础和翻译科学家，患者倡导社区参与。研讨会形式包括邀请讲座，小组讨论,以及观众讨论和评论的机会。
结果：在研讨会前的调查中，接受调查的92％的泌尿科医生认为，卡介苗替代品的开发是卡介苗的高风险患者的高药物开发优先事项。讨论的关键主题包括疾病状态的定义；卡介苗NMIBC的试验设计，卡介苗原位癌无反应，和BCG无反应的乳头状癌;单臂试验设计的优势和局限性;评估患者报告的结局;以及评估避免膀胱切除术作为疗效指标的考虑因素。
结论：研讨会讨论了在NMIBC中改进试验设计的几个重要机会。FDA鼓励赞助商在药物开发早期与适当的审查部门会面，讨论NMIBC的试验设计方案。
