Identifying prescribing cascades in Alzheimer's disease and related dementias: The calcium channel blocker-diuretic prescribing cascade.

PURPOSE: Prescribing cascades occur when a physician prescribes a new drug to address the side-effect of another drug. Persons with Alzheimer's disease and related dementias (ADRD) are at increased risk for prescribing cascades. Our objective was to develop an approach to estimating the proportion of calcium channel blocker-diuretic (CCB-diuretic) prescribing cascades among persons with ADRD in two U.S. health plans. METHODS: We identified patients aged ≥50 on January 1, 2017, dispensed a drug to treat ADRD in the 365-days prior to/on cohort entry date. Patients had medical/pharmacy coverage for 1 year before and through cohort entry. We excluded individuals with an institutional stay encounter in the 45 days prior to cohort entry and censored patients based on: disenrollment from coverage, death, or end of data. We identified incident and prevalent CCB use in the 183-days following cohort entry, and identified subsequent incident diuretic use among incident and prevalent CCB-users within 365-days from cohort entry. RESULTS: There were 121 538 eligible patients. Approximately 62% were female, with a mean age of 79.5 (SD ±8.6). Overall 2.1% of the cohort experienced a prevalent CCB-diuretic prescribing cascade with 1586 incident diuretic-users among 36 462 prevalent CCB-users (4.3%, 95% CI 4.1-4.6%]); and there were161 incident diuretic-users among 3304 incident CCB-users (4.9%, 95% CI 4.2-5.7%) (incident CCB-diuretic cascade). CONCLUSIONS: We describe an approach to identify prescribing cascades in persons with ADRD, which can be used to assess the proportion of prescribing cascades in large cohorts. We determined the proportion of CCB-diuretic prescribing cascades was low.

Antidopaminergic-Antiparkinsonian Medication Prescribing Cascade in Persons with Alzheimer's Disease.

OBJECTIVES: Persons living with Alzheimer's disease (AD) may be at increased risk for prescribing cascades due to greater multimorbidity, polypharmacy, and the need for more complex care. Our objective was to assess the proportion of the antidopaminergic-antiparkinsonian medication prescribing cascades among persons living with Alzheimer's disease. SETTING: Two large administrative claims databases in the United States. PARTICIPANTS: We identified patients aged ≥50 on January 1, 2017, who were dispensed a drug used to treat Alzheimer's disease for at least 1 day in the 365 days prior to or on cohort entry date and who had medical and pharmacy coverage in the 365 days prior to the cohort entry date. We excluded individuals with a recent institutional stay. We identified incident antidopaminergic (antipsychotic/metoclopramide) use in the 183 days following cohort entry and identified subsequent incident antiparkinsonian drug use within 8 to 365 days. RESULTS: There were 121,538 patients with Alzheimer's disease eligible for inclusion. Approximately 62% were women with a mean age of 79.5 (SD ± 8.6). The mean number of drugs dispensed was 9.2 (SD ± 4.9). There were 36 incident antiparkinsonian users among 4,534 incident antipsychotic/metoclopramide users (0.8%). CONCLUSION: We determined that the proportion of antidopaminergic-antiparkinsonian medication prescribing cascades, widely considered as high-priority, was low. Our approach can be used to assess the proportion of prescribing cascades in populations considered to be at high risk and to prioritize system-level interventional efforts to improve medication safety in these patients.

PCORnet® 2020: current state, accomplishments, and future directions.

OBJECTIVE: To describe PCORnet, a clinical research network developed for patient-centered outcomes research on a national scale. STUDY DESIGN AND SETTING: Descriptive study of the current state and future directions for PCORnet. We conducted cross-sectional analyses of the health systems and patient populations of the 9 Clinical Research Networks and 2 Health Plan Research Networks that are part of PCORnet. RESULTS: Within the Clinical Research Networks, electronic health data are currently collected from 337 hospitals, 169,695 physicians, 3,564 primary care practices, 338 emergency departments, and 1,024 community clinics. Patients can be recruited for prospective studies from any of these clinical sites. The Clinical Research Networks have accumulated data from 80 million patients with at least one visit from 2009 to 2018. The PCORnet Health Plan Research Network population of individuals with a valid enrollment segment from 2009 to 2019 exceeds 60 million individuals, who on average have 2.63 years of follow-up. CONCLUSION: PCORnet's infrastructure comprises clinical data from a diverse cohort of patients and has the capacity to rapidly access these patient populations for pragmatic clinical trials, epidemiological research, and patient-centered research on rare diseases.

Prescribing cascades in persons with Alzheimer's disease: engaging patients, caregivers, and providers in a qualitative evaluation of print educational materials.

INTRODUCTION: Prescribing cascades occur when the side effect of a drug is misinterpreted as a new medical condition, and a second drug is prescribed to address the side effect. Persons with Alzheimer's disease (AD) are at increased risk of prescribing cascades due to greater multimorbidity, polypharmacy, and complexity of care. The objective of this study was to evaluate educational materials about prescribing cascades in persons with AD, and elicit input on their use in a future trial. METHODS: We interviewed community-dwelling adults with either an AD diagnosis or a prescription drug used to treat AD (n = 12), caregivers of patients meeting the same criteria (n = 14), and providers (n = 15). We coded interview transcripts and organized themes according to the communication-human information processing model. We revised the materials based on the interviews, and surveyed participating caregivers and providers for their reactions to the revised materials. RESULTS: Analysis of patients', caregivers', and providers' comments suggest: (a) Providers had conflicting views about the messaging of materials; (b) Caregivers were likely to read letters addressed to patients; (c) Providers were likely to ignore letters, but were receptive to patient/caregiver-initiated conversations; (d) Patients and caregivers had difficulty understanding prescribing cascades; (e) Providers worried that mailed materials would undermine trust; (f) Participants had mixed views on how materials might affect the clinical encounter; (g) Participants felt that materials would improve patient/caregiver engagement. When surveyed, most providers found the revised materials informative and actionable, and most caregivers found them understandable and useful. CONCLUSIONS: This evaluation of educational materials about prescribing cascades in patients with AD provides strong support for engaging caregivers to communicate with providers about prescribing cascades. By giving patients and caregivers a basic description of the prescribing cascade concept, our educational materials may help them prepare for a conversation with the provider, who can then tailor the discussion of the possible cascade to the specific needs of the individual patient and caregiver. However, evidence on whether materials can stimulate such conversations awaits testing in a future trial. LAY SUMMARY: Patient, caregiver and provider thoughts on educational materials about prescribing and medication safety Prescribing cascades occur when the side effect of a medication is misinterpreted as a new medical condition, and a second medication is prescribed to treat the side effect. Persons with Alzheimer's disease (AD) are at increased risk of prescribing cascades because they often have more medical conditions, more medications, and more complex care. The goal of this study was to evaluate mailed educational materials about prescribing cascades in persons with AD, and get input on their use in a future study. We interviewed 12 adults with AD, or prescribed a medication to treat AD, 14 caregivers of persons with AD, and 15 providers. We reviewed the interview transcripts to identify important findings about our educational materials. We edited the materials based on the interviews, and sent participating caregivers and providers a questionnaire to get their reactions to the new materials. Important findings from the interviews suggest: (a) Providers had conflicting views about the recommendations given; (b) Caregivers were likely to read letters addressed to patients; (c) Providers were likely to ignore letters, but were receptive to patients/caregivers introducing the topic; (d) Patients and caregivers had difficulty understanding prescribing cascades; (e) Providers worried mailed materials would undermine trust; (f) Participants had mixed views on how materials might affect a doctor's appointment; (g) Participants felt strongly that materials would improve patient/caregiver engagement. When surveyed, almost all providers found the revised materials informative and actionable; and most caregivers found them understandable and useful. These findings provide strong support for engaging caregivers to communicate with providers about prescribing cascades. The educational materials may help patients and caregivers prepare for a conversation with the provider, who can then tailor the discussion of the possible cascade to the specific needs of the individual patient and caregiver. However, evidence on whether materials can stimulate such conversations awaits testing in a future study.

Diagnosed prevalence of Alzheimer's disease and related dementias in Medicare Advantage plans.

INTRODUCTION: One-third of Medicare beneficiaries are enrolled in Medicare Advantage (MA). Yet, little is known about MA beneficiaries diagnosed with Alzheimer's disease (AD) and AD-related dementias (AD/ADRD). METHODS: We calculated the prevalence of AD/ADRD diagnoses in 2014 and 2016 in three MA plans. We determined the demographic characteristics of beneficiaries diagnosed with AD/ADRD, and whether they disenrolled from the MA plan for any reason within 364 days from the index date. RESULTS: In 2014 and 2016, the overall prevalence of AD/ADRD diagnoses was 5.6% and 6.5%, respectively. In 2016, AD/ADRD beneficiaries were on average 82.4 (SD = 7.4) years of age, 61.8% female, and had multiple comorbidities. By 364 days post-index date, 32% of beneficiaries with AD/ADRD had disenrolled from their plan. The demographic characteristics of 2014 beneficiaries with diagnosed AD/ADRD were similar to their 2016 counterparts. DISCUSSION: The prevalence of AD/ADRD diagnosis in MA is lower than rates reported in Medicare fee-for-service.

The Patient-Centered Outcomes Research Network Antibiotics and Childhood Growth Study: Implementing Patient Data Linkage.

PCORnet, the Patient-Centered Outcomes Research Network, is comprised of health systems and health plans that transform electronic health records (EHRs) and claims data to a common data model (CDM) to facilitate real-world clinical research. Because patients receive health care in multiple care delivery settings, linking health records across systems and health plan claims would provide a more comprehensive and accurate picture of health care for patients. The current study expanded on a PCORnet Antibiotics and Childhood Growth (ABX) study to (1) identify and implement a privacy-preserving patient linkage solution among a clinical data research network and a health plan network within the ABX Study, and (2) assess overlap in prescribed and dispensed antibiotics and additional data gained from claims among the linked patients. This manuscript describes the linkage process and resulting overlap analysis. The authors identified 549 patients from the EHR record study cohort who had claims records with the health plan. Sixty percent (n = 329) of patients had consistent antibiotic exposure data across the 2 sources, indicating antibiotic exposure (44.3%) or nonexposure (15.7%). Among total antibiotic prescribing records, 43.1% had a matched claims record for dispensing within 60 days. Among antibiotic dispense records 26.5% were not associated with a prescribing record in the linked health systems. These findings showcase the feasibility of linking health plan claims data to PCORnet CDM in a privacy-preserving manner while also demonstrating continued gaps in data that may occur. The study highlights the importance of combining multiple health data sources for comprehensive clinical research.

Cross-Network Directory Service: Infrastructure to enable collaborations across distributed research networks.

INTRODUCTION: Existing large-scale distributed health data networks are disconnected even as they address related questions of healthcare research and public policy. This paper describes the design and implementation of a fully functional prototype open-source tool, the Cross-Network Directory Service (CNDS), which addresses much of what keeps distributed networks disconnected from each other. METHODS: The set of services needed to implement a Cross-Directory Service was identified through engagement with stakeholders and workgroup members. CNDS was implemented using PCORnet and Sentinel network instances and tested by participating data partners. RESULTS: Web services that enable the four major functional features of the service (registration, discovery, communication, and governance) were developed and placed into an open-source repository. The services include a robust metadata model that is extensible to accommodate a virtually unlimited inventory of metadata fields, without requiring any further software development. The user interfaces are programmatically generated based on the contents of the metadata model. CONCLUSION: The CNDS pilot project gathered functional requirements from stakeholders and collaborating partners to build a software application to enable cross-network data and resource sharing. The two partners-one from Sentinel and one from PCORnet-tested the software. They successfully entered metadata about their organizations and data sources and then used the Discovery and Communication functionality to find data sources of interest and send a cross-network query. The CNDS software can help integrate disparate health data networks by providing a mechanism for data partners to participate in multiple networks, share resources, and seamlessly send queries across those networks.

Prospective surveillance pilot of rivaroxaban safety within the US Food and Drug Administration Sentinel System.

PURPOSE: The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance. METHODS: In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of 36 173 rivaroxaban and 79 520 warfarin initiators were variable-ratio matched within 2 monitoring periods. RESULTS: Statistically significant signals were observed for ischemic stroke (IS) (first period) and intracranial hemorrhage (ICH) (second period) favoring rivaroxaban, and gastrointestinal bleeding (GIB) (second period) favoring warfarin. In follow-up analyses using primary position diagnoses from inpatient encounters for increased definition specificity, the hazard ratios (HR) for rivaroxaban vs warfarin new users were 0.61 (0.47, 0.79) for IS, 1.47 (1.29, 1.67) for GIB, and 0.71 (0.50, 1.01) for ICH. For GIB, the HR varied by age: <66 HR = 0.88 (0.60, 1.30) and 66+ HR = 1.49 (1.30, 1.71). CONCLUSIONS: This study demonstrates the capability of Sentinel to conduct prospective safety monitoring and raises no new concerns about rivaroxaban safety.

A Comparative Assessment of Observational Medical Outcomes Partnership and Mini-Sentinel Common Data Models and Analytics: Implications for Active Drug Safety Surveillance.

INTRODUCTION: An often key component to coordinating surveillance activities across distributed networks is the design and implementation of a common data model (CDM). The purpose of this study was to evaluate two drug safety surveillance CDMs from an ecosystem perspective to better understand how differences in CDMs and analytic tools affect usability and interpretation of results. METHODS: Humana claims data from 2007 to 2012 were mapped to Observational Medical Outcomes Partnership (OMOP) and Mini-Sentinel CDMs. Data were described and compared at the patient level by source code and mapped concepts. Study cohort construction and effect estimates were also compared using two different analytical methods--one based on a new user design implementing a high-dimensional propensity score (HDPS) algorithm and the other based on univariate self-controlled case series (SCCS) design--across six established positive drug-outcome pairs to learn how differences in CDMs and analytics influence steps in the database analytic process and results. RESULTS: Claims data for approximately 7.7 million Humana health plan members were transformed into the two CDMs. Three health outcome cohorts and two drug cohorts showed differences in cohort size and constituency between Mini-Sentinel and OMOP CDMs, which was a result of multiple factors. Overall, the implementation of the HDPS procedure on Mini-Sentinel CDM detected more known positive associations than that on OMOP CDM. The SCCS method results were comparable on both CDMs. Differences in the implementation of the HDPS procedure between the two CDMs were identified; analytic model and risk period specification had a significant impact on the performance of the HDPS procedure on OMOP CDM. CONCLUSIONS: Differences were observed between OMOP and Mini-Sentinel CDMs. The analysis of both CDMs at the data model level indicated that such conceptual differences had only a slight but not significant impact on identifying known safety associations. Our results show that differences at the ecosystem level of analyses across the CDMs can lead to strikingly different risk estimations, but this can be primarily attributed to the choices of analytic approach and their implementation in the community-developed analytic tools. The opportunities of using CDMs are clear, but our study shows the need for judicious comparison of analyses across the CDMs. Our work emphasizes the need for ongoing efforts to ensure sustainable transparent platforms to maintain and develop CDMs and associated tools for effective safety surveillance.

Validation of acute myocardial infarction in the Food and Drug Administration's Mini-Sentinel program.

PURPOSE: To validate an algorithm based upon International Classification of Diseases, 9(th) revision, Clinical Modification (ICD-9-CM) codes for acute myocardial infarction (AMI) documented within the Mini-Sentinel Distributed Database (MSDD). METHODS: Using an ICD-9-CM-based algorithm (hospitalized patients with 410.x0 or 410.x1 in primary position), we identified a random sample of potential cases of AMI in 2009 from four Data Partners participating in the Mini-Sentinel Program. Cardiologist reviewers used information abstracted from hospital records to assess the likelihood of an AMI diagnosis based on criteria from the Joint European Society of Cardiology and American College of Cardiology Global Task Force. Positive predictive values (PPVs) of the ICD-9-based algorithm were calculated. RESULTS: Of the 153 potential cases of AMI identified, hospital records for 143 (93%) were retrieved and abstracted. Overall, the PPV was 86.0% (95% confidence interval; 79.2%, 91.2%). PPVs ranged from 76.3% to 94.3% across the four Data Partners. CONCLUSIONS: The overall PPV of potential AMI cases, as identified using an ICD-9-CM-based algorithm, may be acceptable for safety surveillance; however, PPVs do vary across Data Partners. This validation effort provides a contemporary estimate of the reliability of this algorithm for use in future surveillance efforts conducted using the Food and Drug Administration's MSDD.

The organizational structure and governing principles of the Food and Drug Administration's Mini-Sentinel pilot program.

The US Food and Drug Administration's Mini-Sentinel pilot program is developing an organizational structure as well as principles and policies to govern its operations. These will inform the structure and function of the eventual Sentinel System. Mini-Sentinel is a collaboration that includes 25 participating institutions. We describe the program's current organizational structure and its major principles and policies. The organization includes a coordinating center with program leadership provided by a principal investigator; a planning board and subcommittees; an operations center; and data, methods, and protocol cores. Ad hoc workgroups are created as needed. A privacy panel advises about protection of individual health information. Principles and policies are intended to ensure that Mini-Sentinel conforms to the principles of fair information practices, protects the privacy of individual health information, maintains the security and integrity of data, assures the confidentiality of proprietary information, provides accurate and timely communications, prevents or manages conflicts of interest, and preserves respect for intellectual property rights.

Design considerations, architecture, and use of the Mini-Sentinel distributed data system.

PURPOSE: We describe the design, implementation, and use of a large, multiorganizational distributed database developed to support the Mini-Sentinel Pilot Program of the US Food and Drug Administration (FDA). As envisioned by the US FDA, this implementation will inform and facilitate the development of an active surveillance system for monitoring the safety of medical products (drugs, biologics, and devices) in the USA. METHODS: A common data model was designed to address the priorities of the Mini-Sentinel Pilot and to leverage the experience and data of participating organizations and data partners. A review of existing common data models informed the process. Each participating organization designed a process to extract, transform, and load its source data, applying the common data model to create the Mini-Sentinel Distributed Database. Transformed data were characterized and evaluated using a series of programs developed centrally and executed locally by participating organizations. A secure communications portal was designed to facilitate queries of the Mini-Sentinel Distributed Database and transfer of confidential data, analytic tools were developed to facilitate rapid response to common questions, and distributed querying software was implemented to facilitate rapid querying of summary data. RESULTS: As of July 2011, information on 99,260,976 health plan members was included in the Mini-Sentinel Distributed Database. The database includes 316,009,067 person-years of observation time, with members contributing, on average, 27.0 months of observation time. All data partners have successfully executed distributed code and returned findings to the Mini-Sentinel Operations Center. CONCLUSION: This work demonstrates the feasibility of building a large, multiorganizational distributed data system in which organizations retain possession of their data that are used in an active surveillance system.

Penetration of medication safety technology in community hospitals.

Results of a survey of medication safety technology in community hospitals are presented. A written questionnaire was mailed to pharmacy directors at 88 hospitals located in 21 states. Items in the questionnaire addressed current and planned use of technology intended to improve medication safety. Fifty-six usable responses were received for a response rate of 63.6%. Medication safety was considered one of the most important issues facing pharmacy departments. Barriers identified by respondents to the implementation of medication safety initiatives included lack of time and personnel. Most hospitals had implemented one or more different types of medication safety technology. Computer-generated or electronic medication administration records, pharmacy computer systems interfaced with laboratory values, and unit-based medication dispensing cabinets were the most common medication safety technologies used. Pharmacy managers perceived these technologies to have resulted in a reduction in the rate of medication errors in respondent hospitals.