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

基本信息

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
项目类别：
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

项目摘要

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规定的阿片类药物通常会导致昂贵且不可预测的不利影响，包括生命 - 易受伤害的患者威胁呼吸道抑郁症和长期阿片类药物使用/滥用。美国FDA警告由于术后缺氧脑损伤和死亡而反对儿童使用可待因和曲马多，并且由于严重的呼吸问题和婴儿死亡，在护理母亲中。有一个紧急且未得到关键的需要积极的风险识别和个性化的精确镇痛以提高安全性和有效性弱势群体中的阿片类药物。主动的精确药物，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；成本效益并建立的基因分型保险可以最大程度地减少阿片类药物的过量使用和相关的危害与当前的反复试验，反应性医学。使用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，在此阶段1 STTR应用中，Opalgenix， Inc.提议验证护理母亲及其他们的不良阿片类药物结局的遗传特征剖宫产后的婴儿。 Opalgenix团队将与学术研究人员合作，并利用非 - 重叠的NIH R01资金（HD089458和HD096800），以补充此STTR申请以追求以下两个目的：1）验证并确定与术后阿片类药物不良相关的遗传危险因素在接受剖宫产及其母乳喂养的新生儿的成年妇女和2）中的影响。发展保险公司报销术前遗传风险预测和决策的多基因实验室开发测试（LDT）支持小儿和成人手术患者，以防止阿片类药物不良结局。 Opalgenix将开发最低可行产品（MVP），一个由CLIA认证实验室中的精制多基因面板组合药物遗传学预测和决策支持，以个性化手术镇痛算法在儿童和成人中使用精确的阿片类药物。这有望防止普通阿片类药物不良结果，例如呕吐和罕见的生命威胁和妥协结果，例如呼吸抑郁，慢性弱势儿科和成人手术队列。未来的II期STTR将重点介绍CLIA LDT的FDA预批准，以识别遗传性的患者预先鉴定为严重的不良阿片类药物结局，包括过量，OUD和新生儿阿片类药物戒断联合体（NOWS）。根据当前的阿片类流行病，预计$ 2.15 仅在美国，阿片类药物的经济负担仅在美国，这是一个重要的商业市场 Opalgenix的存在可主动识别并有效地减少术后阿片类药物相关的不良反应， CPSP，Oud，Nows和用药过量，同时每年数以百万计的美国人的手术缓解。