Neyt Mattias, Christiaens Annick, Aloi Marina, de Ridder Lissy, Croft Nicholas M, Koletzko Sibylle, Levine Arie, Turner Dan, Russell Richard K, Ruemmele Frank M, Veereman Gigi
Medical Evaluation and Technology Assessment (ME-TA), Merendree, Belgium.
Pediatric Gastroenterology and Nutrition, University Hospital Brussels, Brussels, Belgium.
JMIR Form Res. 2021 Jan 25;5(1):e13888. doi: 10.2196/13888.
The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years).
The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished.
The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD's National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected.
A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children's school attendance and parents' productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument.
The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children's and parents' QoL (EuroQol 5-Dimension questionnaires), children's school attendance, and parents' productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial.
ClinicalTrials.gov NCT02852694; https://clinicaltrials.gov/ct2/show/NCT02852694.
开展REDUCE - RISK试验旨在比较在儿科人群（6 - 17岁）中，每周皮下注射甲氨蝶呤与每日口服硫唑嘌呤或6 - 巯基嘌呤用于低风险克罗恩病（CD）的疗效，以及皮下注射阿达木单抗（ADA）用于高风险CD的疗效。
本研究的目的是进行系统评价，为研究方案提供参考，以便在试验结束时收集必要信息，以改进基于证据的经济评估。
查阅了循证医学中心（CRD）卫生技术评估（HTA）数据库、HTA机构网站、CRD的国民健康服务经济评估数据库、MEDLINE（OVID）和Embase数据库，以检索相关经济评估（的综述）。若研究纳入了使用ADA（修美乐）治疗的患有炎症性肠病（CD和溃疡性结肠炎[UC]）的儿科或成人人群，则该研究符合条件。对对照物无限制。仅选择以获得的生命年数或获得的质量调整生命年数表示结果的经济评估。
共识别出12项主要研究。由于缺乏支持性试验，这些研究均未纳入儿科人群。我们系统评价中识别出的经济评估表明，ADA是纳入此类试验的合适干预措施。从卫生经济学角度来看，对这种干预措施与标准治疗进行增量分析很重要，而不是立即与另一种（昂贵的）生物治疗进行比较。经济评估目前缺乏关于儿童上学出勤率和父母生产力影响的信息，且基础试验均未使用通用效用工具测量生活质量（QoL）。
对ADA治疗CD患者的经济文献进行综述支持在儿科患者中开展生物制剂试验，包括根据疾病严重程度进行区分。进行经济文献综述使我们能够从经济角度决定应在研究方案中添加哪些变量。儿童和父母的QoL测量（欧洲五维健康量表问卷）、儿童上学出勤率和父母生产力（工作生产力和活动障碍问卷 - CD - 综合版）已添加到研究方案中。这将为计算REDUCE - RISK试验中评估的干预措施成本效益提供支持。
ClinicalTrials.gov NCT02852694；https://clinicaltrials.gov/ct2/show/NCT02852694
