Potter Beth K, Hutton Brian, Clifford Tammy J, Pallone Nicole, Smith Maureen, Stockler Sylvia, Chakraborty Pranesh, Barbeau Pauline, Garritty Chantelle M, Pugliese Michael, Rahman Alvi, Skidmore Becky, Tessier Laure, Tingley Kylie, Coyle Doug, Greenberg Cheryl R, Korngut Lawrence, MacKenzie Alex, Mitchell John J, Nicholls Stuart, Offringa Martin, Schulze Andreas, Taljaard Monica
School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Drive, Ottawa, ON, K1G 5Z3, Canada.
Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Trials. 2017 Dec 19;18(1):603. doi: 10.1186/s13063-017-2327-3.
Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. There are important evidence gaps related to the comparative effectiveness of therapies for IMD, which are in part due to challenges in conducting randomized controlled trials (RCTs) for rare diseases. Registry-based RCTs present a unique opportunity to address these challenges provided the registries implement standardized collection of outcomes that are important to patients and their caregivers and to clinical providers and healthcare systems. Currently there is no core outcome set (COS) for studies evaluating interventions for paediatric IMD. This protocol outlines a study that will establish COS for each of two relatively common IMD in children, phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.
This two-part study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Part 1 includes a rapid review and development of an evidence map to identify a comprehensive listing of outcomes reported in past studies of PKU and MCAD deficiency. The review follows established methods for knowledge synthesis, including a comprehensive search strategy, two stages of screening citations against inclusion/exclusion criteria by two reviewers working independently, and extraction of important data elements from eligible studies, including details of the outcomes collected and outcome measurement instruments. The review findings will inform part 2 of our study, a set of Delphi surveys to establish consensus on the highest priority outcomes for each condition. Healthcare providers, families of children with PKU or MCAD deficiency, and health system decision-makers will be invited to participate in two to three rounds of Delphi surveys. The design of the surveys will involve parents of children with IMD who are part of a family advisory forum.
This protocol is a crucial step in developing the capacity to launch RCTs with meaningful outcomes that address comparative effectiveness questions in the field of paediatric IMD. Such trials will contribute high-quality evidence to inform decision-making by patients and their family members, clinicians, and policy-makers.
遗传性代谢疾病（IMD）是一大类罕见的单基因疾病，通常在生命早期被诊断出来。关于IMD治疗的比较有效性，存在重要的证据空白，部分原因是开展罕见病随机对照试验（RCT）面临挑战。基于注册库的RCT提供了一个独特的机会来应对这些挑战，前提是注册库实施对患者及其照护者、临床提供者和医疗保健系统重要的标准化结局收集。目前，在评估儿科IMD干预措施的研究中，尚无核心结局集（COS）。本方案概述了一项研究，该研究将为儿童中两种相对常见的IMD——苯丙酮尿症（PKU）和中链酰基辅酶A脱氢酶（MCAD）缺乏症——分别建立COS。
这项分为两部分的研究已在有效性试验核心结局指标（COMET）倡议中注册。第1部分包括快速回顾和证据图谱的制定，以确定过去PKU和MCAD缺乏症研究中报告的结局的全面清单。该回顾遵循既定的知识综合方法，包括全面的检索策略、由两名独立工作的评审员根据纳入/排除标准对文献进行两轮筛选，以及从符合条件的研究中提取重要数据元素，包括所收集结局的详细信息和结局测量工具。回顾结果将为我们研究的第2部分提供信息，即一系列德尔菲调查，以就每种疾病的最高优先级结局达成共识。将邀请医疗保健提供者、PKU或MCAD缺乏症患儿的家庭以及卫生系统决策者参与两到三轮德尔菲调查。调查设计将涉及作为家庭咨询论坛一部分的IMD患儿家长。
本方案是发展开展具有有意义结局的RCT的能力的关键一步，这些结局将解决儿科IMD领域的比较有效性问题。此类试验将提供高质量证据，为患者及其家庭成员、临床医生和政策制定者的决策提供参考。
