Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan). Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds

Examining sociodemographic correlates of opioid use, misuse, and use disorders in the All of Us Research Program

BACKGROUND: The All of Us Research Program enrolls diverse US participants which provide a unique opportunity to better understand the problem of opioid use. This study aims to estimate the prevalence of opioid use and its association with sociodemographic characteristics from survey data and electronic health record (EHR). METHODS: A total of 214,206 participants were included in this study who competed survey modules and shared EHR data. Adjusted logistic regressions were used to explore the associations between sociodemographic characteristics and opioid use. RESULTS: The lifetime prevalence of street opioids was 4%, and the nonmedical use of prescription opioids was 9%. Men had higher odds of lifetime opioid use (aOR: 1.4 to 3.1) but reduced odds of current nonmedical use of prescription opioids (aOR: 0.6). Participants from other racial and ethnic groups were at reduced odds of lifetime use (aOR: 0.2 to 0.9) but increased odds of current use (aOR: 1.9 to 9.9) compared with non-Hispanic White participants. Foreign-born participants were at reduced risks of opioid use and diagnosed with opioid use disorders (OUD) compared with US-born participants (aOR: 0.36 to 0.67). Men, Younger, White, and US-born participants are more likely to have OUD. CONCLUSIONS: All of Us research data can be used as an indicator of national trends for monitoring the prevalence of receiving prescription opioids, diagnosis of OUD, and non-medical use of opioids in the US. The program employs a longitudinal design for routinely collecting health-related data including EHR data, that will contribute to the literature by providing important clinical information related to opioids over time. Additionally, this data will enhance the estimates of the prevalence of OUD among diverse populations, including groups that are underrepresented in the national survey data

Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19:A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country -level estimates of 90 -day absolute risk (with 95% confidence intervals) of ATE and VTE. Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID19 vaccines were available (through November 2020). The 90 -day absolute risk of ATE during this period ranged from 0.11% (0.09- 0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90 -day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90 -day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90 -day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99- 1.04%) in the US. Conclusion: There was heterogeneity by country in 90 -day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability. Plain Language Summary: Cohort studies of patients diagnosed with COVID-19 in both the ambulatory and hospital settings have suggested that SARS-CoV-2 infection promotes hypercoagulability that could lead to arterial or venous thromboembolism. However, few studies have examined how the risk of thromboembolism with COVID-19 has evolved over time across different countries. A new collaboration was established among the regulatory authorities of Canada, Europe, and the US within the International Coalition of Medicines Regulatory Authorities to evaluate the 90 -day risk of both arterial and venous thromboembolism after initial diagnosis of COVID-19 in the ambulatory or hospital setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. The study found that there was variability in the risk of both arterial and venous thromboembolism by month across the countries among patients initially diagnosed with COVID-19 in the ambulatory or hospital setting. Differences in the healthcare systems, prevalence of comorbidities in the study cohorts, and approaches to the case definitions of thromboembolism likely contributed to the variability in estimates of thromboembolism risk across the countries

Crusade for Cancer Data: How a Non-SEER Site Populated the Virtual Data Warehouse Tumor Table

Background: The virtual data warehouse (VDW) tumor table is a valuable data resource available to Cancer Research Network (CRN) researchers to examine the feasibility of potential projects or to conduct research. The Surveillance, Epidemiology and End-Results (SEER) registry provides timely and efficient data for VDW tumor tables. HealthPartners Institute (HPI) is a non-SEER site that has developed alternative approaches (claims-based algorithms, medical record review) to obtain tumor data and participate in cancer-related research. These approaches can identify false-positive cases, be time-consuming and be costly. Methods: Over the past 15 years, HPI has undertaken numerous activities to identify a viable electronic data source to populate the VDW tumor table and thereby more readily participate in multisite studies within the CRN. These activities included two internally-funded capacity-building projects. The first, conducted in 2009, examined the ability to connect with the population-based cancer registry Minnesota Cancer Surveillance System, maintained by the Minnesota Department of Health (MDH), to identify cancer cases with specific diagnostic and treatment criteria preparatory to research. In 2011, our second project explored linking with the electronic registry system (ERS) at an HPI-owned hospital, Regions. More recently, HPI increased its tumor registry case ascertainment with the inclusion of care centers in Eastern Minnesota and Western Wisconsin as well as the merging of another health system, Park Nicollet. Results: The 2009 feasibility project demonstrated that MDH was able to link 79% of cases identified by HPI claims data. Nonmatches occurred from misclassification by HPI-created algorithms, patients not living in Minnesota, or patients with cancers different from those identified by HP records. Concordance for determining eligibility (stage, date of diagnosis) was high, but not 100%. The 2011 feasibility project demonstrated that HPI programmers can access Regions cancer registry data directly via the ERS similar to other data sources (eg, Clarity, Epic) through procurement of a software license and training. The project programmer extracted registry cases from ERS, mapped data elements to variables outlined in the VDW tumor tables and performed quality assurance checks provided by the VDW tumor work group. Thus, ERS data is currently our electronic source for the VDW tumor table. Following the expansion of the HPI care network to include Lakeview Hospital and three Cancer Center of Western Wisconsin sites (Westfields Hospital and Clinic, Amery Hospital and Clinic, Hudson Hospital and Clinic) along with the 2014 merger of HPI and Park Nicollet organizations, HPI is currently extracting tumor data from the ERS at these sites and Park Nicollet Methodist Hospital. Ongoing efforts to enhance the HPI tumor file include obtaining any available tumor information from MDH for all HPI patients and members. Conclusion: After time and vigorous exploration, HPI’s tumor data is part of the CRN Cancer Counter. More recent activities have enriched this data. HPI is in a better position to not only conduct internal cancer research, but also to participate in multisite studies. A visual timeline of the activities undertaken to identify and connect with tumor data sources, as well as the challenges, successes and proposed future work, will be presented

Unique Case Report of a Meningeal Sarcoma Arising during Ongoing Treatment for Progressing Intraparenchymal Glioma

Radiation-induced sarcomas in the brain are extremely rare, usually occur with an average latency of 9 years, and are associated with poor outcomes. Latency periods shorter than 1 year may indicate a genetic predisposition such as Li-Fraumeni syndrome. A 34-year-old man underwent initial tumor resection and radiation therapy for a World Health Organization (WHO) Grade II Astrocytoma. Within 6 months, the tumor recurred as WHO Grade III and was treated with temozolomide and then bevacizumab. Despite the patient’s apparent improving condition, MRI revealed new dural-based lesions 10 months after radiation therapy and identified as high-grade sarcoma. The patient resumed bevacizumab, began NovoTTF treatment for progressing glioma, and ifosfamide/doxorubicin for the sarcoma. Genetic testing revealed no pathogenic mutation in the TP53 gene. Ultimately, treatment was unsuccessful and the patient succumbed to glioma and sarcoma within 2 years of initial diagnosis. This case was unique due to the rapidly progressing glioma and sudden appearance of a high-grade sarcoma. It is unusual to have two separate intracranial primary cancers with each requiring a different chemotherapy regimen. We discuss the difficulty of simultaneously treating with separate chemotherapy regimens. It remains unclear whether the sarcoma was induced by the radiation treatment or a genetic predisposition

Applying a Model to Predict Neutropenia Risk in Patients With Cancer Using Electronic Data

Background/Aims: Granulocyte-colony stimulating factors (G-CSFs) are indicated to decrease the incidence of infections associated with chemotherapy-induced neutropenia (a severe reduction in white blood cells) in cancer patients receiving myelosuppressive chemotherapy. Severe neutropenia or febrile neutropenia occurs in 25–40% of treatment-naïve patients and are associated with increased infection rates, treatment delays, dose reductions, hospitalizations, deaths and increased costs. In addition to the chemotherapy treatment regimen, patient-specific factors influence neutropenic risk. Current guideline recommendations do not include a mechanism to quantify patient risk when determining need to G-CSF support. Studies report over- and underuse of G-CSF among those at low and high risk for neutropenia. A neutropenia risk model developed by Lyman et al. showed prior chemotherapy, relative dose intensity (RDI), abnormal liver and renal function, and low white cell count are major risk factors. We are testing the feasibility of using readily available clinical and administrative data from the HealthPartners electronic medical record and Oncology Treatment Module to apply the Lyman model to data from adult cancer patients receiving first cycle chemotherapy. Methods: We included breast, colorectal, lymphoid, lung and ovarian cancer patients to compare abstracted chart data to electronically extracted data. We will adapt the Lyman model to predict neutropenia risk using our database. We also will extract electronic data from our site’s virtual data warehouse (VDW) for comparison with sites participating in a separate CRN-funded pilot project to evaluate the feasibility of using VDW data to predict neutropenic risk. Results: We identified and abstracted data on 235 patients who received one of 60 treatment regimens. The median age at diagnosis was 61 (range 30–86) and 32% were male. Of those, 92 (39%) received G-CSF. The most commonly administered chemotherapy included cyclophosphamide, etoposide, 5-fluorouracil and doxorubicin. Manually abstracted data will be used to validate the electronically extracted data. Data validation, including inter-rater reliability and RDI, is ongoing. Discussion: G-CSF use among chemotherapy patients can be identified in electronic oncology treatment records. Validation of key variables to determine the feasibility of using electronic data for risk determination is ongoing

Opioid Prescribing During Pregnancy: Eight-Year Secular Trends at HealthPartners Medical Group

Background: Nationally, opioid prescribing for chronic noncancer pain has increased significantly over the last 20 years. Recently published evidence suggests that 20% to 40% of women received opioid prescriptions of varying doses and durations during pregnancy, which may cause increased risks of harm to mother and fetus. The purpose of this retrospective observational study was to determine the prevalence of opioid prescribing 3 months before pregnancy, each trimester of pregnancy and 3 months postpartum, as well as the secular utilization trend over an 8-year period, among member-patients at HealthPartners Medical Group (HPMG). Methods: All pregnant member-patients of HPMG who delivered a live birth from 2006 to 2014 and had continuous pharmacy benefits beginning 3 months prior to their estimated pregnancy start through 3 months postpartum were included. Demographic, clinical, pharmaceutical and provider variables of interest were identified and described. Significant opioid prescribing during pregnancy was defined as more than 5 days’ supply prescribed in any 3-month period, excluding the 2-week postpartum period. Time trends for 2006–2014 were examined using linear regression. Results: Of 11,565 pregnancies during the study period, significant opioid prescribing during 3 months before pregnancy, pregnancy or 3 months postpartum were observed in 862 (7.5%) pregnancies (816 unique women). A total of 454 (3.9%) pregnant women received significant opioid prescriptions during one or more trimesters of their pregnancy. From 2006 to 2014, the rate of significant opioid prescribing during each trimester of pregnancy and 3 months before and after pregnancy decreased -0.2% per year. Conclusion: Significant opioid prescribing during the three trimesters of pregnancy as well as 3 months before and after pregnancy for member-patients of HPMG was significantly lower than reported studies from other populations and locations across the United States over the last 15 years. Furthermore, significant opioid prescribing was trending downward slightly over time, rather than rising as reported elsewhere. Explanatory factors for these findings should be explored

Applying a Neutropenia Risk Model to Cancer Patients Using VDW Data: A CRN Pilot Study

Background/Aims: Neutropenia, an extreme reduction in infection-fighting white blood cells, is a dangerous side effect of cytotoxic chemotherapy for cancer treatment, especially when accompanied by fever. Neutropenia and febrile neutropenia are associated with treatment delays, chemotherapy dose reductions, hospitalizations, antibiotic use, death and high costs. The granulocyte-colony stimulating factors (G-CSFs), filgrastim, pegfilgrastim and tbo-filgrastim, reduce the risk of neutropenia and febrile neutropenia; however, they are also associated with additional patient visits, side effects and high treatment-related costs. G-CSF use was found to be inconsistent with recommended clinical guidelines (overuse among those at low risk and underuse among those at high risk for neutropenia), thus making it part of the Choosing Wisely campaign. Individual patient factors are associated with increased risk for neutropenia and febrile neutropenia beyond that of the prescribed chemotherapy. No study has investigated the effect of providing medical oncologists with neutropenia risk predictions in real time to optimize the use of G-CSF and reduce neutropenia/febrile neutropenia outcomes among patients. The ongoing work will assess the feasibility of applying an existing patient neutropenia risk model developed by Lyman et al. to existing electronic data files. This work builds upon feasibility work currently being conducted at HealthPartners Institute, Minneapolis, MN, and adds two more CRN sites (Group Health Research Institute, Seattle, WA, and Henry Ford Health System, Detroit, MI). Methods: We will investigate the applicability of an adapted risk model to readily available electronic data (excluding clinical oncology treatment modules). We will adapt Lyman’s model to work with available data, provide external validation and calibrate the adapted model for our patient population. Results: To date, we have obtained IRB approval to conduct the study and are developing a distributed modular program for extraction of clinical and administrative data variables available in the HMORN’s virtual data warehouse. Discussion: This presentation will report preliminary data on neutropenia and febrile neutropenia rates, chemotherapy treatment variations and G-CSF use among racially and geographically diverse sites. The current CRN study will provide a necessary foundation for a planned external proposal designed to test and implement a real-world risk assessment tool intended for use by clinicians at the point of care

Opioid Prescribing During Pregnancy: Eight-Year Secular Trends at HealthPartners Medical Group

Background: Nationally, opioid prescribing for chronic noncancer pain has increased significantly over the last 20 years. Recently published evidence suggests that 20% to 40% of women received opioid prescriptions of varying doses and durations during pregnancy, which may cause increased risks of harm to mother and fetus. The purpose of this retrospective observational study was to determine the prevalence of opioid prescribing 3 months before pregnancy, each trimester of pregnancy and 3 months postpartum, as well as the secular utilization trend over an 8-year period, among member-patients at HealthPartners Medical Group (HPMG). Methods: All pregnant member-patients of HPMG who delivered a live birth from 2006 to 2014 and had continuous pharmacy benefits beginning 3 months prior to their estimated pregnancy start through 3 months postpartum were included. Demographic, clinical, pharmaceutical and provider variables of interest were identified and described. Significant opioid prescribing during pregnancy was defined as more than 5 days’ supply prescribed in any 3-month period, excluding the 2-week postpartum period. Time trends for 2006–2014 were examined using linear regression. Results: Of 11,565 pregnancies during the study period, significant opioid prescribing during 3 months before pregnancy, pregnancy or 3 months postpartum were observed in 862 (7.5%) pregnancies (816 unique women). A total of 454 (3.9%) pregnant women received significant opioid prescriptions during one or more trimesters of their pregnancy. From 2006 to 2014, the rate of significant opioid prescribing during each trimester of pregnancy and 3 months before and after pregnancy decreased -0.2% per year. Conclusion: Significant opioid prescribing during the three trimesters of pregnancy as well as 3 months before and after pregnancy for member-patients of HPMG was significantly lower than reported studies from other populations and locations across the United States over the last 15 years. Furthermore, significant opioid prescribing was trending downward slightly over time, rather than rising as reported elsewhere. Explanatory factors for these findings should be explored