Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design.

Background And Aims: Primary biliary cholangitis (PBC) is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with PBC in whom ursodeoxycholic acid (UDCA) failed, based on a surrogate endpoint of reduction in alkaline phosphatase. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients.

Lessons learned from a multi-data source research collaboration: The mirabegron post-authorization safety study program.

Background: Many factors contribute to developing and conducting a successful multi-data source, non-interventional, post-authorization safety study (NI-PASS) for submission to multiple health authorities. Such studies are often large undertakings; evaluating and sharing lessons learned can provide useful insights to others considering similar studies.

Objectives: We discuss challenges and key methodological and organizational factors that led to the delivery of a successful post-marketing requirement (PMR)/PASS program investigating the risk of cardiovascular and cancer events among users of mirabegron, an oral medication for the treatment of overactive bladder.

Effectiveness of BNT162b2 COVID-19 primary series vaccination in children aged 5-17 years in the United States: a cohort study.

Background: COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study's objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children.

Methods: This cohort study identified children aged 5-17 years vaccinated with BNT162b2 matched with unvaccinated children.

Safety of Ancestral Monovalent BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 Vaccines in US Children Aged 6 Months to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials.

Objective: To conduct near-real-time monitoring of health outcomes after COVID-19 vaccination in the US pediatric population.

Design, Setting, And Participants: This cohort study evaluated 21 prespecified health outcomes after exposure before early 2023 to BNT162b2, mRNA-1273, or NVX-CoV2373 ancestral monovalent COVID-19 vaccines in children aged 6 months to 17 years by applying a near-real-time monitoring framework using health care data from 3 commercial claims databases in the US (Optum [through April 2023], Carelon Research [through March 2023], and CVS Health [through February 2023]).

Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry.

Purpose: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions.

Incidence rates of thrombosis with thrombocytopenia syndrome (TTS) among adults in United States commercial and Medicare claims databases, 2017-2020.

Background: Increased risk of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector-based COVID-19 vaccinations has been identified in passive surveillance systems. TTS incidence rates (IRs) in the United States (U.S.

Effectiveness of monovalent COVID-19 booster/additional vaccine doses in the United States.

Background: Monovalent booster/additional doses of COVID-19 vaccines were first authorized in August 2021 in the United States. We evaluated the real-world effectiveness of receipt of a monovalent booster/additional dose of COVID-19 vaccine compared with receiving a primary vaccine series without a booster/additional dose.

Methods: Cohorts of individuals receiving a COVID-19 booster/additional dose after receipt of a complete primary vaccine series were identified in 2 administrative insurance claims databases (Optum, CVS Health) supplemented with state immunization information system data between August 2021 and March 2022.

Pragmatic guidance for embedding pragmatic clinical trials in health plans: Large simple trials aren't so simple.

Background: There are unique opportunities related to the design and conduct of pragmatic trials embedded in health insurance plans, which have longitudinal data on member/patient demographics, dates of coverage, and reimbursed medical care, including prescription drug dispensings, vaccine administrations, behavioral healthcare encounters, and some laboratory results. Such trials can be large and efficient, using these data to identify trial-eligible patients and to ascertain outcomes.

Methods: We use our experience primarily with the National Institutes of Health Pragmatic Trials Collaboratory Distributed Research Network, which comprises health plans that participate in the US Food & Drug Administration's Sentinel System, to describe lessons learned from the conduct and planning of embedded pragmatic trials.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials.

Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years.

Design, Setting, And Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration.

Use of Immunization Information Systems in Ascertainment of COVID-19 Vaccinations for Claims-Based Vaccine Safety and Effectiveness Studies.

Importance: Safety and effectiveness studies of COVID-19 vaccines are being conducted using clinical data, including administrative claims. However, claims data only partially capture administered COVID-19 vaccine doses for numerous reasons, such as vaccination at sites that do not generate claims for reimbursement.

Objective: To evaluate the extent to which Immunization Information Systems (IIS) data linked to claims data enhances claims-based COVID-19 vaccine capture for a commercially insured population and to estimate the magnitude of misclassification of vaccinated individuals as having unvaccinated status in the linked IIS and claims data.

Cervical High-Grade Squamous Intraepithelial Lesion Burden and Standard of Care Treatment Effectiveness and Safety in the United States, 2008-2018: The EACH-WOMAN Project.

Objective: Management of cervical high-grade squamous intraepithelial lesions (HSILs), the immediate precursor of cervical cancer, consists largely of surgical treatment for women at higher risk for progression to cancer. The authors' objective was to describe the occurrence of cervical HSIL in the United States and various outcomes for women who received surgical treatment.

Methods: From a US commercial health insurer, a cohort of adult women with cervical HSIL diagnoses receiving surgical treatment within 3 months of diagnosis between January 2008 and September 2018 was identified.

Development and Validation of ICD-10-CM-based Algorithms for Date of Last Menstrual Period, Pregnancy Outcomes, and Infant Outcomes.

Introduction And Objective: Validation studies of algorithms for pregnancy outcomes based on International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes are important for conducting drug safety research using administrative claims databases. To facilitate the conduct of pregnancy safety studies, this exploratory study aimed to develop and validate ICD-10-CM-based claims algorithms for date of last menstrual period (LMP) and pregnancy outcomes using medical records.

Methods: Using a mother-infant-linked claims database, the study included women with a pregnancy between 2016-2017 and their infants.

Incident autoimmune conditions among males receiving quadrivalent human papillomavirus vaccine in the United States.

Background: The potential for vaccines to induce autoimmunity has been the subject of considerable investigation and autoimmune induction remains a common focus for vaccine safety research. This study assessed the risk of new onset autoimmune conditions among males receiving the 4-valent human papillomavirus (HPV) vaccine (4vHPV).

Methods: Within a US health insurance claims database, we formed a cohort of male 4vHPV vaccine recipients between 2009 and 2016, along with a propensity score matched cohort of males who did not receive the 4vHPV vaccine.

Background rates of adverse events of special interest for COVID-19 vaccine safety monitoring in the United States, 2019-2020.

Background: The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination.

Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years.

Background: Active monitoring of safety outcomes following COVID-19 vaccination is critical to understand vaccine safety and can provide early detection of rare outcomes not identified in pre-licensure trials. We present findings from an early warning rapid surveillance system in three large commercial insurance databases including more than 16 million vaccinated individuals.

Methods: We evaluated 17 outcomes of interest following COVID-19 vaccination among individuals aged 12-64 years in Optum, HealthCore, and CVS Health databases from December 11, 2020, through January 22, 2022, January 7, 2022, and December 31, 2021, respectively.

Trends in COVID-19 patient characteristics in a large electronic health record database in the United States: A cohort study.

Background: Electronic health record (EHR) databases provide an opportunity to facilitate characterization and trends in patients with COVID-19.

Methods: Patients with COVID-19 were identified based on an ICD-10 diagnosis code for COVID-19 (U07.1) and/or a positive SARS-CoV-2 viral lab result from January 2020 to November 2020.

Safety of 4-valent human papillomavirus vaccine in males: a large observational post-marketing study.

The 4-valent human papillomavirus (HPV) vaccine (4vHPV vaccine), Gardasil®, is indicated for the prevention of several HPV-related diseases. The objective was to assess the safety of 4vHPV vaccine administered to males as part of routine care. The study used a US health insurance claims database, and included males, age 9 to 26 years, who initiated 4vHPV between October 2009 and December 2016.

Delayed pregnancy detection and return to fertility with extended levonorgestrel-containing oral contraceptives: A real world setting cohort study.

Purpose: As part of the European risk management plan of a 91-day extended levonorgestrel-containing combined oral contraceptive (COC ), a study was performed to assess its safety. This analysis was conducted to examine delayed pregnancy detection and return to fertility with extended combined oral contraceptives (COC).

Methods: We conducted a retrospective cohort study in new users of 91-day COC or 28-day COC within a US-based healthcare claims database from 2006 to 2017.

Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases.

Background: Several passive surveillance systems reported increased risks of myocarditis or pericarditis, or both, after COVID-19 mRNA vaccination, especially in young men. We used active surveillance from large health-care databases to quantify and enable the direct comparison of the risk of myocarditis or pericarditis, or both, after mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccinations.

Methods: We conducted a retrospective cohort study, examining the primary outcome of myocarditis or pericarditis, or both, identified using the International Classification of Diseases diagnosis codes, occurring 1-7 days post-vaccination, evaluated in COVID-19 mRNA vaccinees aged 18-64 years using health plan claims databases in the USA.

Identification of pregnancies and infants within a US commercial healthcare administrative claims database.

Purpose: Health care insurance claims databases are becoming a more common data source for studies of medication safety during pregnancy. While pregnancies have historically been identified in such databases by pregnancy outcomes, International Classification of Diseases, 10th revision Clinical Modification (ICD-10-CM) Z3A codes denoting weeks of gestation provide more granular information on pregnancies and pregnancy periods (i.e.

Patterns of Utilization and Expenditure Across Multiple Sclerosis Disease-Modifying Therapies: A Retrospective Cohort Study Using Claims Data from a Commercially Insured Population in the United States, 2010-2019.

Introduction: Comparisons of healthcare utilization and expenditure among multiple sclerosis (MS) disease-modifying therapies (DMTs) are limited.

Methods: In this retrospective cohort study using commercial insurance claims data of a US population (2010-2019), we compared healthcare utilization and costs in MS across different DMTs. We assigned patients to different treatment arms: no DMT (ND), high-efficacy (HE) DMT (alemtuzumab, B cell depletion, cladribine, and natalizumab), and standard-efficacy (SE) DMT (dimethyl fumarate, glatiramer acetate, interferon beta, sphingosine-1-phosphate receptor modulator, and teriflunomide).

Predictors of critical care, mechanical ventilation, and mortality among hospitalized patients with COVID-19 in an electronic health record database.

Background: There are limited data on risk factors for serious outcomes and death from COVID-19 among patients representative of the U.S.

Population: The objective of this study was to determine risk factors for critical care, ventilation, and death among hospitalized patients with COVID-19.

Treatment characteristics among patients with binge-eating disorder: an electronic health records analysis.

Objectives: Treatment for adults diagnosed with binge-eating disorder (BED) includes psychotherapy and/or pharmacotherapy and aims to reduce the frequency of binge-eating episodes and disordered eating, improve metabolic-related issues and reduce weight, and address mood symptoms. Data describing real-world treatment patterns are lacking; therefore, this study aims to characterize real-world treatment patterns among patients with BED.

Methods: This retrospective study identified adult patients with BED using natural language processing of clinical notes from the Optum electronic health record database from 2009 to 2015.

Retrospective Observational Real-World Outcome Study to Evaluate Safety Among Patients With Erectile Dysfunction (ED) With Co-Possession of Tadalafil and Anti-Hypertensive Medications (anti-HTN).

Background: Erectile dysfunction (ED) is a common condition affecting male adults and may be associated with hypertension, diabetes, hyperlipidemia, and obesity. Phosphodiesterase type 5 (PDE5) inhibitors, such as tadalafil, are the first-line drug therapy for ED. Studies and the current prescribing information of these PDE5 inhibitors indicate they are mechanistic mild vasodilators and, as such, concomitant use of a PDE5 inhibitor with anti-hypertensive medication may lead to drops in blood pressure due to possible drug-drug interaction.