MICA: Meeting global need to improve newborn care through real-world-health-data-facilitated, digital-technology-supported randomised clinical trials

目的和目标：我们的目标是减少进行随机对照试验（RCT）的成本、负担和时间，以改善对生病和早产儿的护理，并开发满足他们需求的药物、诊断和设备。随机对照试验是检验治疗方法最可靠、最公平的方法，因为每个病人都有平等的机会接受最好的治疗方法。数据收集是随机对照试验的主要成本，因此我们将使用已在我们建立的高质量存储库英国国家新生儿研究数据库（NNRD）中可用的记录数据作为临床护理的一部分。我们还将使用数字技术和创新的研究设计。NNRD-RCT的想法很简单，但安全传输数据、开发和实施稳健、透明的操作程序、确保对流程的信任以及大规模交付解决方案的技术过程很复杂，这也是我们的主要目标。需求：新生儿护理是一个巨大的国家和全球需求的领域。新生儿健康决定人生轨迹；例如，早产或体重过重或过轻的婴儿在成年后患糖尿病或高血压等慢性疾病的风险高达8倍，这将使健康预期寿命减少多达15-20年。虽然改善他们的健康有终身的好处，但新生儿在获得生物医学创新方面处于不利地位，因为在进行涉及他们的随机对照试验方面存在实际或想象的困难。迄今为止，只有一种专门针对新生儿疾病开发的药物，而且90%以上用于治疗婴儿的药物在安全性、剂量和有效性方面的数据不足，因为它们只在老年患者中进行了评估。这很危险，因为药物在婴儿身上的作用方式通常与其他年龄组非常不同。另一个困难是，可靠地解决医疗保健的不确定性往往需要大量婴儿的参与；例如，为了确定一种治疗方法是否能将严重的早产儿视网膜病变（儿童失明的主要原因）减少25%，将需要进行一项涉及约14,000名婴儿的研究，这将是昂贵的、困难的，并且需要很长时间。因此，许多RCT，虽然需要，但从来没有做过，或太小或质量差。其结果是，即使在常规护理方面也存在许多不确定性，例如早产儿的最佳营养类型，以及减少感染风险的最佳方法。我们将做什么：我们将创建标准操作流程，将数据从NNRD传输到RCT主文件、电子表格和数字工具，例如用于自动提醒和员工培训。我们将获得利益相关者的观点，以建立对NNRD-RCT的理解和信任，并为商业RCT发展多媒体通信和透明、管理良好的流程。我们将让利益相关者参与开发两个范例NNRD-RCT（以解决临床护理中长期存在的优先级不确定性，并评估新生儿药物）。我们还将开发统计和设计解决方案，最大限度地提高nrd - rct的效率。产出将包括帮助临床研究人员的资源，以及对行业研究人员的指导。需要建立合作伙伴关系的原因：需要建立合作伙伴关系，以汇集符合监管标准的可扩展技术解决方案方面的专业知识，开发NNRD-RCT设计方案，确保利益相关者的参与和参与，并创建有影响力的沟通。我们的合作伙伴是Bliss（国家患病和早产婴儿慈善机构）、Health Data Research UK（国家健康数据科学研究所）、Neonatal Society（临床研究协会）、Strategic Intelligence Alliance for Healthcare（支持NHS和行业的中小企业）、OpenClinica（临床试验云技术提供商）和UK Medicines and Healthcare products Regulatory Agency。开发的资源、技术诀窍和知识将提供给世界各地的所有临床试验单位和研究人员。

AIMS AND OBJECTIVES: We aim to reduce the cost, burden, and time to conduct randomised controlled trials (RCT) to improve the care of sick and preterm babies and develop medicines, diagnostics and devices that meet their needs. RCT are the most reliable and fair way to test treatments because every patient has an equal chance of receiving the best approach. Data collection is a major cost of RCT hence we will use data recorded as part of clinical care that is already available in a high-quality repository we established, the UK National Neonatal Research Database (NNRD). We will also use digital technologies and innovative study designs. The idea for NNRD-RCT is simple but the technical processes to flow data securely, develop and implement robust, transparent operational procedures, ensure trust in processes, and deliver solutions at scale, are complex, and our principal objectives. NEED: Neonatal care is an area of great national and global need. Newborn health sets trajectories for life; e.g. a baby born preterm, or over or underweight, is at up to 8 times greater risk of developing a chronic disease like diabetes or high blood pressure in adult life, that will decrease healthy life expectancy by as much as 15-20 years. Though improving their health has life-long benefits, newborn babies are disadvantaged in accessing biomedical innovations because of real or perceived difficulties in conducting RCT involving them. There has only ever been a single medicine specifically developed for a newborn condition, and over 90% of medicines used to treat babies have inadequate data on safety, dose, and efficacy because they have only been evaluated in older patients. This is dangerous because the way in which medicines work in babies is often very different from other age groups. Another difficulty is that reliably resolving healthcare uncertainties often requires the participation of large numbers of infants; e.g. to identify whether a treatment reduces severe retinopathy of prematurity, the major cause of childhood blindness, by 25%, would require a study involving about 14,000 infants which would be costly, difficult, and take a long time. Therefore many RCT, though needed, are never done or are too small or poor quality. The consequence is that there are many uncertainties in even routine aspects of care such as the best type of nutrition for preterm babies, and the best way to reduce the risk of infection. WHAT WE WILL DO: We will create standard operating processes to flow data from the NNRD to RCT master-files and electronic forms and digital tools e.g. for automated reminders and staff training. We will obtain stakeholder perspectives to build understanding and trust in NNRD-RCT and develop multi-media communications and transparent, well-governanced processes for commercial RCT. We will involve stakeholders in developing two exemplar NNRD-RCT (to resolve a long-standing, priority-ranked uncertainty in clinical care and to evaluate a neonatal medicine). We will also develop statistical and design solutions that maximise NNRD-RCT efficiency. Outputs will include resources to help clinical investigators, and guidance for industry researchers. WHY A PARTNERSHIP IS NEEDED: A partnership is needed to bring together expertise in scalable technical solutions that meet regulatory standards, develop NNRD-RCT design options, secure stakeholder involvement and engagement, and create impactful communications. Our partners are Bliss (national charity for sick and preterm babies), Health Data Research UK (national institute for health data science), Neonatal Society (clinical research society), Strategic Intelligence Alliance for Healthcare (SME supporting the NHS and industry), OpenClinica (provider of clinical trial cloud technologies) and UK Medicines and Healthcare products Regulatory Agency. The resources developed, know-how and knowledge, will be available to all clinical trials units and researchers around the world.