Translating genomic discovery to improve care for patients.
The Center embarked on its first project in 2011, the 1200 Patients Project, which uses a preemptive medical system model that reduces the use of high risk medications. Later, CPT established the ACCOuNT Project, Impress Trial, PhOCus Trial.
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The 1200 Patients Project
The 1200 Patients Project aims to develop a new model for personalized medical care through preemptive pharmacogenomics.
Enrolled patients provide a single blood sample for analysis, which is genotyped by an in-house CLIA-certified laboratory. Patients’ genetic information is compared to a database of well-substantiated pharmacogenomic research compiled by the 1200 Patients Project team, which is constantly updated to reflect the most current research available. This database is used to determine whether it is likely that a patient will respond positively or negatively to a medication. With patient permission, these results are delivered to enrolled physicians at the University of Chicago through an online portal, termed the Genomic Prescribing System (GPS).
The GPS is designed to be convenient to use, with clear and consistent images and wording, so that pharmacogenomic information can be easily integrated into clinicians’ workflow. Ultimately, the GPS enables physicians to make patient-specific treatment decisions, improving patient outcomes.
“Finding the Right Medication and Dose”
Adverse reactions to medications are one of the leading causes of death in the United States and many patients take medications that are not effective for them. The information distributed to providers in this study could allow them to identify which patients would experience negative side effects from medications, and to determine which medications would be the most effective for each patient. Pharmacogenomic information can also be factored into dosing algorithms, so that the ideal dose for each patient can be most accurately determined, eliminating the trial-and-error process that is frequently required.
African American Cardiovascular pharmacogenetics CONsorTium (ACCOuNT) is an NIH-supported, multi-institutional group of physicians, researchers, and patients whose goal is to reduce disparity in precision medicine, particularly for African-Americans.
The ACCOuNT Translational project aims to explore the feasibility of implementing preemptive pharmacogenomic result delivery for African-Americans in the inpatient setting across multiple institutions. The ACCOuNT Translational project is led by principal investigator Dr. Peter O’Donnell (University of Chicago) and site leads Drs. Kevin O’Leary (Northwestern University) and Edith Nutescu (University of Illinois at Chicago). Additionally, the ACCOuNT Translational project is supported by the Center for Personalized Therapeutics and other members of ACCOuNT.
“Precision Medicine for All”
The ACCOuNT Translational project is led by principal investigator Dr. Peter O’Donnell (University of Chicago) and site leads Drs. Kevin O’Leary (Northwestern University) and Edith Nutescu (University of Illinois at Chicago). Additionally, the ACCOuNT Translational project is supported by the Center for Personalized Therapeutics and other members of ACCOuNT. There are three specific aims of the translational project.
1. Incorporate race-specific SNPs and recommendations into the GPS.
2. Create a cohort of African-American patients receiving patient care using GPS.
3. Access race-specific recommendations via GPS in consortium institutions.
Self-identified African-American patients who enroll in the ACCOuNT Translational project provide a blood sample which is sent to the Center for Personalized Therapeutics’ CLIA-certified laboratory for genotyping. Genotyping results and clinical decision support are made available within the Genomic Prescribing System (GPS).
Providers who staff inpatient services (physicians, pharmacists, nurse practitioners, and physician assistants) are eligible to enroll for the ACCOuNT Translational project and access patient genotyping results and pharmacogenomic recommendations via the GPS. Each hospital admission at which a preemptively genotyped patient is treated by an enrolled provider is evaluated. Data captured includes provider use of the GPS, as well medications prescribed or administered during the course of the admission. The primary outcome of interest is frequency of GPS use by study providers.
The website for ACCOuNT Project can be found here.
The goal of the ImPreSS Trial is to develop a model for implementing point-of-care pharmacogenomic decision support in the perioperative care setting.
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ImPreSS Trial: Implementation of Point‐of‐Care Pharmacogenomic Decision Support in Perioperative Care
Truong TM, Apfelbaum J, Shahul S, et al. The ImPreSS Trial: Implementation of Point-of-Care Pharmacogenomic Decision Support in Perioperative Care. Clin Pharmacol Ther. 2019;106(6):1179‐1183. doi:10.1002/cpt.1567
Anesthesiologists, critical care and pain management physicians, and associated providers (nurse anesthetists, physician assistants, and pharmacists) within the Department of Anesthesia and Critical Care will be targeted for enrollment through a process of direct stakeholder engagement and informed consent. Adult patients with planned elective inpatient or outpatient surgeries will be eligible for the study.
Enrolled patients provide a DNA sample during their pre-operative clinic at the Anesthesia Perioperative Medicine Clinic (APMC), which is sent to our CLIA-certified laboratory for genotyping, and results will be available before the patient’s surgical admission. Patients’ genotyping results will be delivered to providers through our online web portal, the Genomic Prescribing System (GPS), which is currently integrated into our institutional electronic medical record.
Genotyped patients will be prospectively randomized at the time of surgical admission to one of two treatment arms. In the pharmacogenomics arm, treating providers who care for the patient during the course of the surgical admission will have access to GPS and the patients’ pharmacogenomic information, whereas in the control arm, GPS and patient-specific pharmacogenomic information will be withheld from the providers, approximating current standard of care. We hope this study will advance our understanding of the use of genetic information in the perioperative setting.
Our institutional Data and Analytics Core will be utilized for a key sub-analysis to collect pain care quality data and assess pain management services for both arms, including pain assessment, pain therapy administration, and rate of opioid-induced adverse drug events (ADEs). Reported ADEs will be reviewed to determine whether they were due to prescribed or administered medications during the admission, and whether these medication choices were potentially the result of pharmacogenomics related decision-support delivered to providers in the context of this study.
The paper of this study published on Clinicaltrials.gov can be found here.
Studying pharmacogenomic testing in Oncology care
Over 650,000 patients per year are treated with chemotherapy, with the majority reporting side effects. The goal of the PhOCus Trial is to determine whether delivering pharmacogenomic results to oncology providers will help reduce incidence of severe chemotherapy related side effects and toxicities.
Summary of Methodology
Oncology providers, including physicians, pharmacists, physician assistants, and nurses in the gastrointestinal (GI), head and neck, and breast clinics are enrolled and trained on the use of the Genomic Prescribing System (GPS).
Adult patients for whom chemotherapy with fluoropyrimidines (5-fluorouracil or capecitabine) and/or irinotecan is being considered are eligible. Enrolled patients will provide a DNA sample and will be randomized to one of two treatment arms. In the pharmacogenomics (PGx) arm, oncologists will have access to the GPS and patient-specific pharmacogenomic information, which may inform dosing decisions for chemotherapy as well as supportive care medications such as analgesics and antiemetics. In the control arm, care teams will not have access to pharmacogenomic information until 6 months after initiation of chemotherapy, and dosing will be according to standard of care. We hope this study will enhance our understanding of the use of genetic information in cancer care.
Polymorphisms in the DPYD gene can result in enzyme deficiency leading to an increased risk of severe, sometimes fatal toxicities in up to 10% of patients.
Compared to the historical cohort of *2A carriers who received full dosing, the risk of drug-induced death was reduced from 10% to 0% in *2A carriers receiving reduced dosing. Furthermore, the average total treatment cost was modeled as being modestly lower with screening, even when including the screening costs for the entire population.