Bevan Andrew, Saragoussi Delphine, Sayegh Laura, Ringo Moira, Kearney Fiona
Peri- and Post-Approval Studies, Evidera, London, United Kingdom.
Peri- and Post-Approval Studies, Evidera, London, United Kingdom,
Public Health Genomics. 2021;24(3-4):75-88. doi: 10.1159/000514208. Epub 2021 Mar 23.
Natural history (NH) studies, using observational methods, are common in rare and orphan diseases (80% of which have a genetic component). There is profound interest in identifying genetic mutations driving these diseases in these studies to support the formulation of targeted precision medicines. The global regulatory classification of NH studies with novel molecular biomarker collection has not been clearly delineated, presenting researchers with the challenge of determining how these studies are classified and regulated across multiple geographies.
The aim of this investigation was to conduct a review of regulations related to NH studies and genetic testing to elucidate regulatory pathways to inform clinical researchers in the field.
Regulatory provisions for NH studies and genetic testing were obtained from Pharmaceutical Product Development (PPD)'s propriety regulatory intelligence database and by surveying the company's country-specific regulatory experts. A literature search was conducted in the Google Scholar search engine and PubMed for supplementary information.
Nineteen countries were evaluated; 37% classified NH studies with biomarker collection as noninterventional and 26% required regulatory approval (increasing to 47% when molecular biomarker testing was introduced). No regulatory provisions for genetic testing could be identified in 32% of countries, and 58% did not have binding requirements for genetic counseling.
Lack of harmonization of regulations governing NH studies with molecular biomarker collection contributes to the operational complexity of conducting multinational studies in orphan and rare diseases. A set of harmonized international guidelines for these studies would improve efficiency, and this may be on the horizon with the recent adaption of International Conference on Harmonisation (ICH) guideline E18.
利用观察性方法进行的自然史（NH）研究在罕见病和孤儿病中很常见（其中80%具有遗传成分）。在这些研究中，人们对识别导致这些疾病的基因突变有着浓厚兴趣，以支持靶向精准药物的研发。对于收集新型分子生物标志物的NH研究，全球监管分类尚未明确界定，这给研究人员带来了挑战，即要确定这些研究在多个地区如何分类和监管。
本调查的目的是对与NH研究和基因检测相关的法规进行综述，以阐明监管途径，为该领域的临床研究人员提供信息。
NH研究和基因检测的监管规定来自制药产品开发（PPD）的专有监管情报数据库，并通过调查该公司特定国家的监管专家获得。在谷歌学术搜索引擎和PubMed上进行文献检索以获取补充信息。
对19个国家进行了评估；37%将收集生物标志物的NH研究归类为非干预性研究，26%要求获得监管批准（引入分子生物标志物检测时增至47%）。32%的国家未发现基因检测的监管规定，58%的国家对遗传咨询没有约束性要求。
关于收集分子生物标志物的NH研究的法规缺乏协调性，这增加了在孤儿病和罕见病中开展多国研究的操作复杂性。一套统一的国际准则将提高这些研究的效率，随着国际协调会议（ICH）指南E18的最新修订，这一目标可能即将实现。
