Graduate School of Health, University of Technology Sydney, Building 20, 100 Broadway, Chippendale, Sydney, NSW, 2008, Australia.
Sydney School of Public Health, The University of Sydney, Edward Ford Building, A27 Fisher Rd, Sydney, NSW, 2006, Australia.
Trials. 2021 Jul 22;22(1):480. doi: 10.1186/s13063-021-05439-7.
Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for 'what to measure' in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention.
The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomes for research and practice.
In accordance with guidance from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative, this study will consist of five steps: (i) a systematic review of quantitative studies, using narrative synthesis to identify previously reported outcomes, their definitions, and methods of measurement; (ii) a systematic review of qualitative studies using content analysis to identify excerpts related to patient experience and perspectives that can be interpreted as outcomes; (iii) semi-structured focus groups and interviews with patients who have undertaken reproductive genetic carrier screening to identify outcomes of importance to them; (iv) Delphi survey of key stakeholders, including patients, clinicians, and researchers, to refine and prioritise the list of outcomes generated from the previous steps; and (v) a virtual consensus meeting with a purposive sample of key stakeholders to finalise the core outcome set for reporting.
This protocol outlines the core outcome set development process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions. COMET CORE OUTCOME SET REGISTRATION: http://www.comet-initiative.org/Studies/Details/1381 .
生殖遗传携带者筛查是一种可供计划怀孕或在怀孕早期进行的基因检测，旨在了解生育患有严重遗传疾病孩子的风险。对于这种干预措施，“要测量什么”的问题缺乏共识，导致研究结果和测量方法的选择存在异质性。这种结果的异质性对这些研究的质量和可比性产生了影响，并导致文献中缺乏关于该筛查的有力研究证据，无法为政策和决策提供信息。随着生殖遗传携带者筛查在普通人群中的普及，及时研究该干预措施的结果是非常重要的。
核心结局集的制定是一种解决研究中结果异质性问题的既定方法。我们旨在制定生殖遗传携带者筛查的核心结局集，以明确和规范研究和实践的结果。
根据 COMET（有效性试验核心结局测量）倡议的指导，本研究将包括五个步骤：（i）对定量研究进行系统综述，使用叙述性综合方法来确定已报告的结局、它们的定义和测量方法；（ii）对定性研究进行系统综述，使用内容分析方法来确定可解释为结局的与患者体验和观点相关的摘录；（iii）对接受过生殖遗传携带者筛查的患者进行半结构式焦点小组和访谈，以确定对他们重要的结局；（iv）对关键利益相关者（包括患者、临床医生和研究人员）进行德尔菲调查，以完善和优先考虑前几个步骤中生成的结局列表；（v）与关键利益相关者的目的样本进行虚拟共识会议，以最终确定报告的核心结局集。
本方案概述了核心结局集的开发过程及其在基因检测中的新颖应用。该核心结局集将支持生殖携带者筛查研究中结果报告的标准化，并为评价遗传检测和遗传咨询作为健康干预措施的遗传检测文献的发展做出贡献。COMET 核心结局集注册：http://www.comet-initiative.org/Studies/Details/1381。
