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.

Mortality in Patients with Parkinson's Disease-Related Psychosis Treated with Pimavanserin Compared with Other Atypical Antipsychotics: A Cohort Study.

Introduction: Pimavanserin is approved in the USA to treat hallucinations and delusions associated with Parkinson's disease psychosis (PDP).

Objectives: We evaluated mortality in patients with PDP after initiation of pimavanserin or comparator atypical antipsychotics, overall, over time, and across subgroups.

Methods: A cohort of patients aged ≥65 years in the USA with PDP newly initiating pimavanserin or a comparator atypical antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) was identified in 2016-2019 Medicare claims data.

Clinical outcomes and treatment patterns of older adults with dementia-related psychosis by dementia type in the United States.

Background: Little is known about the incidence of clinical events and treatment patterns among older adults with dementia-related psychosis. Given that dementia-related psychosis comprises various dementia types, this study describes the incidence of clinical events and treatment patterns by dementia type after patients with dementia are diagnosed with psychosis.

Methods: Adults aged ≥ 65 years with dementia and newly diagnosed with psychosis were identified in US Medicare claims during 2013-2018.

Validation of cardiovascular outcomes and risk factors in the Clinical Practice Research Datalink in the United Kingdom.

Purpose: Strategies to identify and validate acute myocardial infarction (AMI) and stroke in primary-care electronic records may impact effect measures, but to an unknown extent. Additionally, the validity of cardiovascular risk factors that could act as confounders in studies on those endpoints has not been thoroughly assessed in the United Kingdom Clinical Practice Research Datalink's (CPRD's) GOLD database. We explored the validity of algorithms to identify cardiovascular outcomes and risk factors and evaluated different outcome-identification strategies using these algorithms for estimation of adjusted incidence rate ratios (IRRs).

Assessing the incidence of osteosarcoma among teriparatide users based on Medicare Part D and US State Cancer Registry Data.

Purpose: During preclinical testing, teriparatide caused a dose-dependent increase in the incidence of osteosarcoma in rats. This study compared the incidence rate of osteosarcoma among patients aged ≥65 years treated with teriparatide vs a matched-comparator cohort.

Methods: This population-based comparative-cohort study matched exposure details for each teriparatide user, identified via Medicare Part D prescription claims, and up to four comparators based on age, sex, zip code, date of claim for filled prescription, and number of unique therapeutic classes dispensed.

Patterns of use of antimuscarinic drugs to treat overactive bladder in Denmark, Sweden, and the United Kingdom.

Purpose: To describe the use of antimuscarinic drugs to treat overactive bladder (OAB) in Denmark, Sweden, and the United Kingdom (UK).

Methods: We identified new users of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium aged 18 years or older from the Danish National Registers (2004-2012), the Swedish National Registers (2006-2012), and UK Clinical Practice Research Datalink (2004-2012). Users were followed until disenrollment, cancer diagnosis, death, or study end.

Variation in Cardiovascular Risk Related to Individual Antimuscarinic Drugs Used to Treat Overactive Bladder: A UK Cohort Study.

Background: Blocking muscarinic receptors could have an effect on cardiac function, especially among elderly patients with overactive bladder (OAB).

Study Objective: To investigate the risk of cardiovascular (CV) events in users of antimuscarinic drugs to treat OAB.

Design, Setting, And Participants: Cohort study of new users of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium, 18 years or older, in the United Kingdom's Clinical Practice Research Datalink (CPRD), 2004-2012.

Validation of Cancer Cases Using Primary Care, Cancer Registry, and Hospitalization Data in the United Kingdom.

Background: In the United Kingdom, hospital or cancer registry data can be linked to electronic medical records for a subset of general practices and years.

Methods: We used Clinical Practice Research Datalink data (2004-2012) from patients treated for overactive bladder. We electronically identified provisional cases of 10 common cancers in General Practitioner Online Database data and validated them by medical profile review.

Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias.

Study Objective: To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs).

Design: Retrospective cohort study.

Data Source: United Kingdom's Clinical Practice Research Datalink.

The feasibility of using multiple databases to study rare outcomes: the potential effect of long-acting beta agonists with inhaled corticosteroid therapy on asthma mortality.

Purpose: Long-acting beta agonists (LABAs) when used without concomitant inhaled corticosteroids (ICS) increase the risk of asthma-related deaths, but the effect on asthma-related death of LABA used in combination with ICS therapy is unknown. To address this question, we explored the feasibility of conducting an observational study using multiple US health care data sources.

Methods: Retrospective cohort study to evaluate the likelihood of getting an upper 95% confidence limit ≤1.

Improving the Identification of Out-of-Hospital Sudden Cardiac Deaths in a General Practice Research Database.

Background: The ascertainment of sudden cardiac death (SCD) in electronic health databases is challenging.

Objectives: Our objective was to evaluate the applicability of the validated computer definition of SCD developed by Chung et al. in a retrospective study of SCD and domperidone exposure in the Clinical Practice Research Datalink (CPRD).

Risk of Out-of-Hospital Sudden Cardiac Death in Users of Domperidone, Proton Pump Inhibitors, or Metoclopramide: A Population-Based Nested Case-Control Study.

Introduction: Epidemiological studies have linked domperidone use with serious cardiac arrhythmias, including sudden cardiac death, but data on age, dose, and duration of use are limited.

Objectives: The aim of this study was to assess the risk of out-of-hospital sudden cardiac death associated with domperidone use versus proton pump inhibitors (PPIs), metoclopramide, or non-use of all three medications, and to evaluate the risk of sudden cardiac death in relation to age and domperidone dose.

Methods: This was a population-based case-control study nested in a cohort of subjects aged ≥2 years in the Clinical Practice Research Datalink with one or more prescriptions for domperidone, any PPI, or metoclopramide from 2005 to 2011.

Risk of acute liver injury associated with the use of moxifloxacin and other oral antimicrobials: a retrospective, population-based cohort study.

Study Objective: To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with nonusers of these antimicrobials.

Design: Retrospective, observational cohort study with a nested case-control analysis.

Data Source: HealthCore Integrated Research Database.

Validation of acute liver injury cases in a population-based cohort study of oral antimicrobial users.

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria.

Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture.

Objective: Depot medroxyprogesterone acetate (DMPA) reversibly reduces bone mineral density. To estimate the extent to which DMPA might increase fracture risk, we undertook a retrospective cohort study of fractures in DMPA users and users of non-DMPA contraceptives, using the General Practice Research Database.

Methods: Eligible women were aged younger than 50 years at the qualifying first contraceptive prescription.

A US postmarketing evaluation of the frequency and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years: 2009-2010 season.

The 2007 US approval for use of Ann Arbor strain live attenuated influenza vaccine (LAIV) in children aged 24 through 59 months included precautions against use in (1) children <24 months and children aged 24 through 59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. Results from the third season (2009-2010) of a 3-year study postmarketing commitment to monitor LAIV vaccination rates and frequency of hospitalizations or emergency department visits within 42 days after LAIV are reported here. As in the first 2 seasons, LAIV usage in cohorts 1, 2, and 4 were low relative to those in LAIV-recommended populations.

Predicting protein function by multi-label correlated semi-supervised learning.

Assigning biological functions to uncharacterized proteins is a fundamental problem in the postgenomic era. The increasing availability of large amounts of data on protein-protein interactions (PPIs) has led to the emergence of a considerable number of computational methods for determining protein function in the context of a network. These algorithms, however, treat each functional class in isolation and thereby often suffer from the difficulty of the scarcity of labeled data.

A postmarketing evaluation of the frequency of use and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years.

The 2007 US approval for use of live attenuated influenza vaccine (LAIV) in children aged 24-59 months included precautions against use in (1) children <24 months and children aged 24-59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. A postmarketing commitment was initiated to monitor LAIV use and the frequency of select safety outcomes in these cohorts. Vaccination rates and the frequency of hospitalizations or emergency department visits within 42 days after LAIV and trivalent inactivated influenza vaccine (TIV) administration were estimated from 2007 to 2009 claims data from a health insurance database.

Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study.

Purpose: Limited information from spontaneous reports and results of two case-control studies raised concern about the cardiotoxicity of oral domperidone therapy. This case-control study nested in a retrospective cohort evaluated the combined risk of serious ventricular arrhythmia (SVA) and sudden cardiac death (SCD) in users of domperidone compared with users of proton pump inhibitors (PPIs), or non-users of these medications.

Methods: A cohort of users of domperidone or a PPI from 1990 to 2005 was identified from existing electronic databases of Saskatchewan Health.