COVID-19: The Effectiveness of Silver Diamine Fluoride- Role in Reducing Health Disparities in Young Children(AdminSuppl)

摘要 拟议的行政补编是对支持第三阶段的合作协定的补充 随机临床试验(RCT)，以评估38%氟化银(SDF)的疗效。自卫队成为 该药将于2014年在美国上市，目前正被用于乳牙空洞病变的治疗。早些时候 儿童期龋病(ECC)仍然是美国儿童中最普遍的慢性病之一。它也是世界上 贫困儿童(例如，学前班儿童)最常见的未得到满足的医疗需求。如果允许病情发展而不接受治疗 长期患病可能会对牙科、医疗、社会和生活质量产生广泛的后果。ECC和 严重的ECC(例如，前牙有多个空洞病变或至少一个龋损，发病年龄较早)是 预防费用相对较低，但对儿童和家庭造成极大负担，治疗费用昂贵 一旦病变空化。这在需要广泛治疗或不合作等的幼儿中尤其如此， 在大多数情况下，在医院手术室的全身麻醉下进行治疗是护理的标准。2016年， FDA向医疗保健提供者发出通知，幼儿全身麻醉可能导致永久性 神经损伤，应避免。因此，需要更好的策略来成功地管理空洞性龋齿 年幼儿童的病变。这项RCT将通过针对患有空洞龋损的幼儿来完成 在临床上暴露了牙本质。由于SDF的突破性治疗地位，FDA一直在大力参与 在这项试验的设计，以确保它将满足要求的空洞性龋损“止痛”药物索赔，这是 在美国的创新。本申请中建议的方案已由Advantage Silver Dental Dragment提交， 作为我们合作的一部分，IND 124808的持有者有限责任公司向美国食品和药物管理局提交了一份文件。在一段研究准备阶段之后， 经验丰富的研究团队正在进行一项第三阶段的多中心、随机、安慰剂对照的优势试验， 两个平行小组，共涉及1,144名1-5岁儿童，他们将接受为期8个月的跟踪调查， 评估38%SDF对以下方面的影响：目标1(主要研究目标)-在一次应用后阻止空洞病变，评估时间为 6个月随访；目的2-分别用药2次、间隔6个月止住空洞性皮损，并比较其疗效 在3个月和6个月时使用一次(子目标2a)；目标3-使用两次后疼痛，间隔6个月，并在一次之后 应用(在3个月和6个月进行评估；次级目标3a)；和目标4--家庭一级的成果，包括与口腔健康有关的成果 生活质量(次级目标4a)和治疗满意度和可接受性(次级目标4b)。直接影响和 这一创新项目的意义在于提供和访问一种非侵入性、廉价和易于使用的 为获得有限护理的儿童管理空洞龋损的替代方案可以深刻地改善口腔 通过止损、减轻痛苦、提高生活质量和显著降低成本来实现健康，所有这些都有助于 大大减少了龋齿方面的差异。这一补充请求旨在解决 新冠肺炎疫情对研究参与者的招募、跟踪和留住以及额外成本产生了影响 与能够恢复临床活动和替换132名将不在研究窗口之外的儿童有关。

Summary The proposed Administrative Supplement is an addition to a Cooperative Agreement for support of a Phase III randomized clinical trial (RCT) to assess the effectiveness of 38% silver diamine fluoride (SDF). SDF became available in the U.S. in 2014, and is being used “off label” for management of cavitated lesions in primary teeth. Early childhood caries (ECC) continues to be one of the most prevalent chronic conditions among U.S. children. It also is one of the most common unmet healthcare needs of poor children (e.g., Head Start children). If allowed to progress untreated for long periods of time, the disease can have broad dental, medical, social, and quality of life consequences. ECC and severe-ECC (e.g., multiple cavitated lesions or at least one caries lesion in the anterior teeth, with onset at an early age) is relatively inexpensive to prevent, yet becomes extremely burdensome on the children and families, and expensive to treat once lesions cavitate. This is especially true in young children who need extensive treatment, or are uncooperative, etc., where treatment under general anesthesia, in most cases in hospital operating rooms, is the standard of care. In 2016, the FDA issued a notice to health care providers that general anesthesia in young children can result in permanent neurological damage and should be avoided. Thus, better strategies are needed to successfully manage cavitated caries lesions in young children. This RCT will be accomplished by targeting young children who have cavitated caries lesions that have exposed dentin clinically. Because of the Breakthrough Therapy Status for SDF, FDA has been heavily involved in the design of this trial to ensure it will meet the requirements for a cavitated caries lesion “arrest” drug claim, which is innovative in the U.S. The proposed protocol in this application has been submitted by Advantage Silver Dental Arrest, LLC, holder of IND 124808, to the FDA as part of our collaboration. Following a study preparation period, an experienced research team is conducting a Phase III, multicenter, randomized, placebo-controlled superiority trial, with two parallel groups involving a total of 1,144 children, 1-5 years old, who will be followed over a period of 8 months, to assess the impact of 38% SDF on: Aim 1 (Primary study aim)- arrest of cavitated lesions after one application, assessed at 6 months follow-up; Aim 2- arrest of cavitated lesions after being applied twice, 6 months apart, and compare the effect of one application at 3 and 6 months (Sub-Aim 2a); Aim 3- pain after being applied twice, 6 months apart, and after a single application (assessed at 3 and 6 months; Sub-Aim 3a); and Aim 4- Family-level outcomes, including oral health-related quality of life (Sub-Aim 4a), and treatment satisfaction and acceptability (Sub-Aim 4b). The immediate impact and significance of this innovative project is that provision of and access to a non-invasive, inexpensive, and simple to use alternative to manage cavitated caries lesions for children with limited access to care could profoundly improve oral health by arresting lesions, reducing pain, improving quality of life, and significantly reducing costs, all contributing to substantial reductions in disparities in caries. This supplement request is meant to address some of the impacts that the COVID-19 pandemic has had on recruitment, follow-up and retention of study participants, and additional costs associated with being able to resume clinical activities and replace 132 children that will be out of the study window.