10 Practical Considerations for the Conduct of Multi-National/Database Studies in Pharmacoepidemiology.

Background: Multi-national/database pharmacoepidemiological studies are increasingly used to address questions that require pooled evidence across populations but introduce challenges in design, harmonization, and analysis.

Objective: To share 10 practical considerations and common pitfalls in planning, executing, and reporting multi-national/database studies, with strategies to mitigate them.

Approach: Practical guidance article synthesizing experience from multi-national/database projects and literature-based exemplars; no original data collection.

International Trends in Opioid Prescribing by Age and Sex from 2001 to 2019: An Observational Study Using Population-Based Databases from 18 Countries and One Special Administrative Region.

Objective: To characterize multinational trends and patterns of opioid analgesic prescribing by sex and age.

Design, Setting, And Participants: We studied opioid analgesic prescribing from 2001 to 2019 with common protocol using population-based databases from eighteen countries and one special administrative region.

Main Outcome Measures: We measured opioid prescribing by geographical region, sex and age, estimating annual prevalent, incident, and nonincident opioid prescribing per 100 population with a 95% confidence interval (CI) and meta-analyzed the multinational and regional opioid prescribing with a random-effects model.

Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study.

Background: A subgroup analysis of the COVID-OUT trial's long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post-COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain.

Objectives: To evaluate the effectiveness of metformin in preventing PCC in adults with overweight or obesity who had a recent COVID-19 infection.

Emulating Six Cardiovascular Outcome Trials of Antidiabetic Drugs in Individuals with Type 2 Diabetes: Analyses Based on Real-World Databases from Korea and Taiwan.

With the increasing volume of clinical evidence derived from large-scale Asian real-world data (RWD) and the growing interest in its use in regulatory decision-making, it is important to conduct benchmarking exercises that evaluate whether studies using Asian RWD can generate similar conclusions as randomized controlled trials (RCTs). We aimed to assess whether observational studies based on Korea and Taiwan RWD can yield comparable results with trials by emulating six cardiovascular outcome trials (CVOTs) of antidiabetic drugs in individuals with type 2 diabetes (T2D). We emulated six CVOTs using nationwide claims of Korea and Taiwan.

The short-, medium- and long-term risk and the multi-organ involvement of clinical sequelae after COVID-19 infection: a multinational network cohort study.

ObjectivesTo generate comprehensive evidence on the risk of clinical sequelae involving different organ systems over time after coronavirus disease 2019 (COVID-19) infection.DesignMultinational retrospective cohort study.SettingElectronic medical records from the US, UK, France, Germany and Italy standardised to the Observational Medical Outcomes Partnership Common Data Model.

Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study.

Objective: To assess the association between glucagon-like peptide 1 receptor agonist (GLP-1RA) use and risk of incident thyroid tumors.

Research Design And Methods: The retrospective, active-comparator new-user cohort study used international administrative claims and electronic health record databases. Participants included patients with type 2 diabetes mellitus (T2DM) with prior metformin therapy initiating a GLP-1RA versus new users of sodium-glucose cotransporter 2 inhibitors (SGLT2is), dipeptidyl peptidase 4 inhibitors (DPP-4is), and sulfonylureas (SUs).

A multinational cohort study of trends in survival following dementia diagnosis.

Abatract: BACKGROUND: Information on the survival of people living with dementia over time and across systems can help policymakers understand the real-world impact of dementia on health and social care systems. This multinational cohort study examines the trends in relative mortality risk following a dementia diagnosis.

Methods: A common protocol was applied to population-based data from the UK, Germany, Finland, Canada (Ontario), New Zealand, South Korea, Taiwan and Hong Kong.

Comparative Safety of Second-Line Antihyperglycemic Agents in Older Adults with Type 2 Diabetes: A Multinational Real-World Evidence From LEGEND-T2DM.

Background: As prescribing of newer antihyperglycemic agents expands, there remains limited comparative safety data for older adults-a population particularly vulnerable to adverse drug events and underrepresented in clinical trials. We aimed to evaluate the real-world safety of second-line antihyperglycemic agents among older adults with type 2 diabetes.

Methods: We conducted a multinational cohort study using nine harmonized electronic health record and claims databases from the U.

Use of gabapentinoid treatment and the risk of self-harm: population based self-controlled case series study.

Objective: To estimate the effect of gabapentinoid treatment on self-harm.

Design: A population based self-controlled case series study.

Setting: UK Clinical Practice Research Datalink Aurum database linked to the Hospital Episode Statistics and Office for National Statistics databases.

Psychiatric and neuropsychiatric sequelae of COVID-19 within 2 years: a multinational cohort study.

Background: The long-term psychiatric and neuropsychiatric sequelae of COVID-19 across diverse populations remain not fully understood. This cohort study aims to investigate the short-, medium-, and long-term risks of psychiatric and neuropsychiatric disorders following COVID-19 infection in five countries.

Methods: This population-based multinational network study used electronic medical records from France, Italy, Germany, and the UK and claims data from the USA.

Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort study.

Background: Fluoroquinolones (FQs) are commonly used to treat urinary tract infections (UTIs), but some studies have suggested they may increase the risk of aortic aneurysm or dissection (AA/AD). However, no large-scale international study has thoroughly assessed this risk.

Methods: A retrospective cohort study was conducted using a large, distributed network analysis across 14 databases from 5 countries (United States, South Korea, Japan, Taiwan, and Australia).

Global Trends in Analgesic Opioid Use in Pregnancy: A Retrospective Cohort Study.

Background: Pain is common during pregnancy, yet there are few contemporary studies of opioid use in pregnancy. This study aimed to describe prescription analgesic opioid use during pregnancy across four regions: Oceania (New South Wales, Australia, and New Zealand), North America (Ontario, Canada, and United States), Northern Europe (Denmark, Finland, Iceland, Norway, Sweden, and United Kingdom), and East Asia (Hong Kong, South Korea, and Taiwan).

Methods: A common protocol was applied to population-based data to measure analgesic opioid dispensing or prescriptions during pregnancy before birth in 2000 to 2020.

Comparative cardiometabolic safety and effectiveness of aripiprazole in people with severe mental illness: A target trial emulation.

Background: There is limited and conflicting evidence on the comparative cardiometabolic safety and effectiveness of aripiprazole in the management of severe mental illness. We investigated the hypothesis that aripiprazole has a favourable cardiometabolic profile, but similar effectiveness when compared to olanzapine, quetiapine, and risperidone.

Methods And Findings: We conducted an observational emulation of a head-to-head trial of aripiprazole versus olanzapine, quetiapine, and risperidone in UK primary care using data from the Clinical Practice Research Datalink.

Barcode medication administration system use and safety implications: a data-driven longitudinal study supported by clinical observation.

Objectives: Barcode medication administration (BCMA) systems may improve patient safety with successful integration and use. This study aimed to explore the barriers and enablers for the successful use of a BCMA system by examining the patterns of medication and patient scanning over time and potential safety implications.

Methods: Retrospective longitudinal study informed by prospective clinical observations using data extracted from five hospital wards over the first 16 months after implementation to determine trends in medication and patient scanning rates, reasons for non-compliance and scanning mismatch alerts.

Maternal and pregnancy factors contributing to the association between area deprivation and infant mortality in England: a retrospective cohort study.

Background: Socioeconomic inequality in infant mortality in the UK is rising. This study aims to identify contributory maternal and pregnancy factors that can explain the known association between area deprivation and infant mortality.

Methods: A cohort study was conducted using Clinical Practice Research Datalink (CPRD) primary care data between 2004 and 2019 linked to the Index of Multiple Deprivation (IMD), and infant mortality from the Office for National Statistics death data.

Prescribing of antipsychotics for people diagnosed with severe mental illness in UK primary care 2000-2019: 20-year investigation of who receives treatment, with which agents and at what doses.

Background: Contemporary data relating to antipsychotic prescribing in UK primary care for patients diagnosed with severe mental illness (SMI) are lacking.

Aims: To describe contemporary patterns of antipsychotic prescribing in UK primary care for patients diagnosed with SMI.

Method: Cohort study of patients with an SMI diagnosis (i.

Lithium Use During Pregnancy in 14 Countries.

Importance: In pregnancy, the benefits of lithium treatment for relapse prevention in psychiatric conditions must be weighed against potential teratogenic effects. Currently, there is a paucity of information on how and when lithium is used by pregnant women.

Objective: To examine lithium use in the perinatal period.

The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer.

Introduction: Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management.

Methods: This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015.

Sex-specific comparative outcomes between oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis.

Aims: Women with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes of DOACs in AF.

Methods: PubMed, Embase, Web of Science and Cochrane Library were searched from January 2008 to November 2022.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.

Effect of statin treatment on the risk of cancer in patients with heart failure: A target trial emulation study.

Purpose: A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin treatment on the risk of cancer in patients with HF.