Improving Analgesic Effectiveness and Safety with Proactive Precision Pain Management in Thoracic Surgical Patients with Lung Lesions - PROJECT SUMMARY Thoracic surgery (TS), especially pneumonectomy, lobectomy and segmentectomy, are common and very painful surgeries for lung lesions with high incidence of uncontrolled acute surgical pain, chronic post- thoracotomy pain and excessive opioid use. Those with poorly controlled acute surgical pain are at risk for chronic post-surgical pain (CPSP), long-term opioid use and opioid addiction. One third of patients undergoing minimally invasive thoracic surgery and one-half undergoing thoracotomy will develop chronic post-surgical pain. TS patients are the least likely to be receiving opioids before surgery, yet they have the highest rate of new persistent opioid use after TS compared with other surgical cohorts. Current best practice postoperative pain management includes standardized enhanced recovery after surgery (ERAS) multimodal analgesic approaches that consist of a combination of opioids and non-opioids with the goal of minimizing opioids during and after surgery. While ERAS protocols have reduced immediate perioperative opioid use, they follow a “one size fits all” trial-and-error reactive protocol approach of standardized analgesic selection at the discretion of physicians, and at-risk patients continue to experience uncontrolled pain, CPSP, costly opioid-related AEs, and poor long-term outcomes. Current evidence shows that 30-60% of interindividual responses to opioids are influenced by genetic factors, with demographic and clinical attributes adding additional risk factors. OpalGenix will build on our extensive prior prospective studies of genetic and clinical predictors of postoperative pain, CPSP, and opioid- related adverse outcomes to develop and commercialize OpalGenix’s Genotype-guided Physician Support for Analgesics use, GPS-AnalgesicsTM. GPS-Analgesics will be a pre-operative 510(k) cleared predictive analytic software as a medical device consisting of preoperative genotyping and electronic health record-integrated intelligent analytics to provide personalized risk analysis to proactively predict risk for surgical pain and opioid responses, supporting clinical decision for optimal and safe personalized post-TS pain management. Phase I will confirm accuracy of risk prediction for a combination of multiple biologically relevant candidate genes in 200 adult TS patients in a prospective longitudinal study and develop risk prediction algorithms that innovatively integrate polygenetic and clinical risks (e.g. depression, anxiety, catastrophization) to predict personalized risk for acute surgical pain, inpatient opioid use, CPSP, opioid-induced RD, PONV, excessive sedation, longer hospital stays, persistent opioid use, high cost of care, and opioid dependence. Successful completion of Phase I will demonstrate that OpalGenix’s proprietary, multi-factorial approach to risk prediction has clinical utility in TS patients and will position OpalGenix to submit an IDE application to the FDA for a head-to-heal clinical trial for Phase II. GPS-Analgesics will provide evidence-based risk assessments for personalized ERAS protocols that will enhance surgical pain relief, eliminate CPSP while avoiding opioid-related safety risks.
