Neonatal Medicine, University College London, Elizabeth Garrett Anderson Institute for Women's Health London, London, UK.
Department of Obstetrics and Gynecology, The Royal Women's Hospital, University of Melbourne, Melbourne, VIC, Australia.
Pediatr Res. 2019 Nov;86(5):567-572. doi: 10.1038/s41390-019-0526-1. Epub 2019 Aug 9.
There is significant uncertainty over the role of assessment of long-term neurodevelopmental outcome (LTO) in neonatal clinical trials. A multidisciplinary working group was established to identify key issues in this area and to make recommendations about optimal approaches to evaluate LTO in therapeutic trials in newborns, which can be developed by sponsors and investigators with other key stakeholders. A key consideration for neonatal trials is the potential for the investigational product to cause widespread effects and drives the need to assess outcome in multiple organs. Thus investigators must assess whether the product has an impact on the brain and the potential for it to cause potential effects on LTO. Critically, is assessment of LTO an important direct therapeutic target or a safety outcome? Such decisions and outcomes need to be specific to the product being studied and use published data, only considering expert opinion when prior evidence does not exist. In designing the trial, the balance of benefits, costs, and burdens of assessments to the researcher and families need to be considered. Families and parent advocates should be involved in design and execution of the study. A framework is presented for use by all key stakeholders to determine the need, nature, and duration of LTO assessments in regulatory trials involving newborn infants.
长期神经发育结局（LTO）评估在新生儿临床试验中的作用存在很大的不确定性。成立了一个多学科工作组，以确定该领域的关键问题，并就如何在新生儿治疗性试验中评估 LTO 提出最佳方法的建议，这些建议可以由赞助商和研究人员与其他主要利益相关者共同制定。新生儿试验的一个关键考虑因素是，研究产品可能会产生广泛的影响，因此需要评估多个器官的结果。因此，研究人员必须评估产品是否对大脑有影响，以及其是否有导致 LTO 潜在影响的可能性。关键是，LTO 评估是一个重要的直接治疗目标还是一个安全结局？这些决策和结果需要针对正在研究的产品具体确定，并使用已发表的数据，只有在没有先前证据的情况下才考虑专家意见。在设计试验时，需要考虑到评估对研究人员和家庭的益处、成本和负担之间的平衡。应让家庭和家长倡导者参与研究的设计和实施。为了确定涉及新生儿的监管试验中 LTO 评估的必要性、性质和持续时间，为所有主要利益相关者提供了一个框架。
