Avoiding Adverse Opioid Outcomes with Proactive Precision Care

通过积极的精准护理避免阿片类药物的不良后果

• 批准号: 10257711
• 负责人: Steven R. Plump
• 金额: $ 31.94万
• 依托单位: OPALGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10257711
• 关键词: ABCB1 gene; Abdomen; Absence of pain sensation; Acute; Adult; Adverse effects; Algorithms; American; Analgesics; Anoxic Encephalopathy; Blinded; Brain Death; Breast Feeding; Breastfed infant; Breathing; Burn Trauma; CLIA certified; CYP2D6 gene; Caring; Cesarean section; Cessation of life; Chest; Child; Childhood; Chronic; Clinical; Codeine; Complement; Current Procedural Terminology Codes; Dependence; Discipline of Nursing; Dose; Economic Burden; Effectiveness; Enzymes; Funding; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genotype; Guidelines; Heritability; Hospitalization; Hydrocodone; Indiana; Infant; Inpatients; Insurance Carriers; Insurance Coverage; Laboratories; Legal patent; Life; Liver; Medical center; Medicine; Morbidity - disease rate; Neonatal; Operative Surgical Procedures; Opiate Addiction; Opioid; Outcome; Overdose; Oxycodone; Oxymorphone; POU2F1 gene; Pain; Patients; Pediatric Hospitals; Perioperative; Perioperative Care; Pharmacogenetics; Phase; Physicians; Population; Postoperative Nausea and Vomiting; Postoperative Period; Pregnant Women; Research; Research Personnel; Resources; Risk; Safety; Sedation procedure; Small Business Technology Transfer Research; Spinal Fusion; Standardization; Technology; Testing; Therapeutic; Time; Tonsillectomy; Tramadol; United States National Institutes of Health; Universities; Variant; Ventilatory Depression; Vomiting; Vulnerable Populations; Woman; addiction; adverse outcome; base; cancer pain; chronic pain; cohort; combinatorial; commercially viable technology; cost; cost effective; cost effectiveness; gene panel; genetic association; genetic risk factor; genetic signature; genetic variant; high risk; improved; infant death; innovation; inter-individual variation; medical schools; mortality; neonate; novel; nursing mothers; opioid epidemic; opioid mortality; opioid use; opioid use disorder; opioid withdrawal; pain relief; personalized care; postcesarean section; precision medicine; preempt; prescription opioid; prevent; primary outcome; productivity loss; public health relevance; response; risk prediction; sickle cell crisis; socioeconomics; surgical pain

PROJECT SUMMARY Perioperative and prescribed opioids often result in costly and unpredictable adverse effects, including life- threatening respiratory depression and long-term opioid use/misuse in vulnerable patients. The US FDA warns against the use of codeine and tramadol in children due to postoperative anoxic brain injuries and deaths, and in nursing mothers due to serious breathing problems and infantile death. There is an urgent and unmet critical need for proactive risk identification and personalized precision analgesia to improve safety and effectiveness of opioids in vulnerable populations. Proactive precision medicine, including preoperative genotyping and personalized analgesia based on scientific evidence; regulatory warnings; CPIC guidelines; cost-effectiveness and established insurance coverage for genotyping could minimize excess opioid use and harm associated with the current trial and error, reactive medicine. Using a patent protected innovative multigene combinatorial pharmacogenetic opioid risk prediction and decision algorithm, in this Phase 1 STTR application, OpalGenix, Inc. proposes to validate the genetic signatures of adverse opioid outcomes in nursing mothers and their babies after cesarean deliveries. OpalGenix team will partner with academic researchers and leverage non- overlapping NIH R01 funding (HD089458 and HD096800) to complement this STTR application to pursue the following two aims: 1) Validate and identify genetic risk factors associated with postoperative opioid adverse effects in adult women undergoing cesarean section and their breastfed neonates, and 2). Develop an insurer reimbursed multi-gene laboratory-developed test (LDT) for preoperative genetic risk prediction and decision support for pediatric and adult surgical patients to prevent adverse opioid outcomes. OpalGenix will develop a minimum viable product (MVP), a refined multi-gene panel in a CLIA certified laboratory with a robust combinatorial pharmacogenetic prediction and decision support to personalize surgical analgesia algorithm with precise opioid use in children and adults. This is expected to prevent common opioid adverse outcomes, such as vomiting and rare life threatening and compromising outcomes like respiratory depression, chronic persistent surgical pain (CPSP), opioid dependence, and opioid use disorder (OUD) in vulnerable pediatric and adult surgical cohorts. A future Phase II STTR will focus on the FDA pre-approval for a CLIA LDT to identify patients genetically pre-disposed to significant adverse opioid outcomes including overdose, OUD, and Neonatal Opioid Withdrawal Syndome (NOWS). Based on the current opioid epidemic and projected $2.15 trillion economic burden of opioids between 2020 and 2040 in the US alone, a significant commercial market exists for OpalGenix to proactively identify and effectively reduce postoperative opioid-related adverse effects, CPSP, OUD, NOWS, and overdose while maximizing surgical pain relief in millions of Americans each year.

项目摘要 围手术期和处方阿片类药物往往会导致昂贵和不可预测的不良反应，包括生命， 易受伤害患者的威胁性呼吸抑制和长期阿片类药物使用/误用。美国FDA警告 反对在术后缺氧性脑损伤和死亡的儿童中使用可待因和曲马多， 在哺乳期的母亲由于严重的呼吸问题和婴儿死亡。有一个紧急和未满足的关键 需要主动风险识别和个性化精确镇痛，以提高安全性和有效性 阿片类药物在弱势群体中的应用前瞻性精准医疗，包括术前基因分型和 基于科学证据的个性化镇痛;监管警告; CPIC指南;成本效益 建立基因分型的保险范围可以最大限度地减少阿片类药物的过度使用和相关伤害 目前的试验和错误，反应性药物。使用一种受专利保护的创新多基因组合 药物遗传学阿片类药物风险预测和决策算法，在本1期STTR申请中，OpalGenix， Inc.建议验证哺乳母亲及其母亲的阿片类药物不良结局的遗传特征， 剖腹产后的婴儿OpalGenix团队将与学术研究人员合作，并利用非 重叠NIH R 01资金（HD 089458和HD 096800），以补充此STTR申请， 以下两个目的：1）确定和识别与术后阿片类药物不良反应相关的遗传风险因素 对接受剖宫产术的成年妇女及其母乳喂养的新生儿的影响; 2）。发展保险公司 用于术前遗传风险预测和决策的可报销多基因实验室开发测试（LDT） 支持儿科和成人手术患者预防阿片类药物不良后果。OpalGenix将开发一种 最小可行产品（MVP），一个在CLIA认证实验室中的精制多基因面板，具有强大的 用于个性化手术镇痛算法的组合药物遗传学预测和决策支持 在儿童和成人中精确使用阿片类药物。这有望防止常见的阿片类药物不良后果， 如呕吐和罕见的危及生命和损害结果，如呼吸抑制，慢性 持续性手术疼痛（CPSP）、阿片类药物依赖和阿片类药物使用障碍（OUD）， 成人手术队列。未来的II期STTR将重点关注FDA对CLIA LDT的预批准，以确定 患者在遗传上易发生显著的阿片类药物不良结局，包括过量、OUD和 新生儿阿片类戒断综合征（NOWS）。根据目前的阿片类药物流行情况和预计的2.15美元 2020年至2040年，仅在美国，阿片类药物的经济负担就高达万亿美元，这是一个重要的商业市场 OpalGenix能够主动识别并有效减少术后阿片类药物相关不良反应， CPSP、OUD、NOWS和药物过量，同时最大限度地缓解每年数百万美国人的手术疼痛。