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Abstract：
BACKGROUND: We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases.
METHODS: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize clinical assessments, generate and refine disease activity and damage measures, and monitor the study. Patients were initiated on one of three standardized methotrexate-based treatment regimens (consensus treatment plans, CTPs) and monitored for 1 year. An optional bio-banking sub-study was included.
RESULTS: The target enrollment of 50 patients was achieved over 26 months at 10 sites, with patients enrolled into all CTPs. Enrolled patients were typical for jLS. Study eligibility criteria were found to perform well, capturing patients thought appropriate for treatment studies. Minor modifications to the eligibility criteria, primarily to facilitate recruitment for future studies, were discussed with consensus agreement reached on them by the jLS group. There were marked differences in site preferences for specific CTPs, with half the sites treating all their patients with the same CTP. Most patients (88%) completed the study, and 68% participated in the bio-banking substudy.
CONCLUSIONS: We demonstrate the feasibility of our approach for conducting comparative effectiveness research in a rare pediatric disease. Multi-center collaboration by dedicated investigators who met regularly was a key factor in the success of this project. Other factors that facilitate these studies include having a sufficient number of investigators to enroll in each regimen, and streamlining study approval and management.
METHODS: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize clinical assessments, generate and refine disease activity and damage measures, and monitor the study. Patients were initiated on one of three standardized methotrexate-based treatment regimens (consensus treatment plans, CTPs) and monitored for 1 year. An optional bio-banking sub-study was included.
RESULTS: The target enrollment of 50 patients was achieved over 26 months at 10 sites, with patients enrolled into all CTPs. Enrolled patients were typical for jLS. Study eligibility criteria were found to perform well, capturing patients thought appropriate for treatment studies. Minor modifications to the eligibility criteria, primarily to facilitate recruitment for future studies, were discussed with consensus agreement reached on them by the jLS group. There were marked differences in site preferences for specific CTPs, with half the sites treating all their patients with the same CTP. Most patients (88%) completed the study, and 68% participated in the bio-banking substudy.
CONCLUSIONS: We demonstrate the feasibility of our approach for conducting comparative effectiveness research in a rare pediatric disease. Multi-center collaboration by dedicated investigators who met regularly was a key factor in the success of this project. Other factors that facilitate these studies include having a sufficient number of investigators to enroll in each regimen, and streamlining study approval and management.
摘要：
背景：我们设计并启动了针对青少年局限性硬皮病（jLS）的试点比较有效性研究，关于最佳治疗的证据有限。我们评估了我们使用的过程，关于具体方案和确定实施罕见儿科疾病研究的策略的一般任务。
方法：这是一个前瞻性的，多中心,50名开始治疗的JLS患者的观察性队列研究，由儿童关节炎和风湿病研究联盟（CARRA）的jLS小组于2012年至2015年设计和实施。举行了一系列虚拟和物理会议来设计研究，标准化临床评估，生成和完善疾病活动和损害措施，并监控研究。患者开始接受三种基于甲氨蝶呤的标准化治疗方案之一（共识治疗计划，CTP）并监测1年。包括一项可选的生物银行子研究。
结果：在10个地点的26个月内实现了50名患者的目标招募，纳入所有CTP的患者。登记的患者是典型的jLS。研究合格标准表现良好，捕获认为适合治疗研究的患者。对资格标准进行了较小的修改，主要是为了促进未来学习的招聘，进行了讨论，并由JLS小组达成了共识。特定CTP的网站偏好存在明显差异，一半的地点用相同的CTP治疗所有患者。大多数患者（88%）完成了研究，68%的人参与了生物银行子研究。
结论：我们证明了我们的方法在一种罕见的儿科疾病中进行有效性比较研究的可行性。定期开会的专职调查人员的多中心合作是该项目的成功的关键因素。促进这些研究的其他因素包括有足够数量的研究者参加每个方案，简化研究审批和管理。
方法：这是一个前瞻性的，多中心,50名开始治疗的JLS患者的观察性队列研究，由儿童关节炎和风湿病研究联盟（CARRA）的jLS小组于2012年至2015年设计和实施。举行了一系列虚拟和物理会议来设计研究，标准化临床评估，生成和完善疾病活动和损害措施，并监控研究。患者开始接受三种基于甲氨蝶呤的标准化治疗方案之一（共识治疗计划，CTP）并监测1年。包括一项可选的生物银行子研究。
结果：在10个地点的26个月内实现了50名患者的目标招募，纳入所有CTP的患者。登记的患者是典型的jLS。研究合格标准表现良好，捕获认为适合治疗研究的患者。对资格标准进行了较小的修改，主要是为了促进未来学习的招聘，进行了讨论，并由JLS小组达成了共识。特定CTP的网站偏好存在明显差异，一半的地点用相同的CTP治疗所有患者。大多数患者（88%）完成了研究，68%的人参与了生物银行子研究。
结论：我们证明了我们的方法在一种罕见的儿科疾病中进行有效性比较研究的可行性。定期开会的专职调查人员的多中心合作是该项目的成功的关键因素。促进这些研究的其他因素包括有足够数量的研究者参加每个方案，简化研究审批和管理。
