Masking in Active Comparator Designs in Pharmacovigilance: A Retrospective Bias Analysis on the Spontaneous Reporting of Thiazolidinediones and Cardiovascular Events.

Introduction: Masking is a reporting bias where drug safety signals are muffled by elevated reporting of other medications in spontaneous reporting databases. While the impact of masking is often limited, its effect when using restricted designs, such as active comparators, can be consequential.

Methods: We used data from the US Food and Drugs Administration Adverse Event Reporting System (1999Q3-2013Q3) to study masking in a real-world example.

Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Comparative risk of infection of medications used for type 2 diabetes.

Introduction: Glucose-lowering drugs pose a potential infection risk among individuals with type 2 diabetes. The U.S.

Comparators in Pharmacovigilance: A Quasi-Quantification Bias Analysis.

Background And Objective: It is unclear which comparator is the most appropriate for bias reduction in disproportionality analyses based on spontaneous reports. We conducted a quasi-quantitative bias analysis using two well-studied drug-event combinations to assess how different comparators influence the directionality of bias in pharmacovigilance.

Methods: We used the US Food and Drug Administration Adverse Event Reporting System focusing on two drug-event combinations with a propensity for stimulated reporting: rivaroxaban and hepatotoxicity, and canagliflozin and acute kidney injury.

Fluoroquinolones and the risk of severe hypoglycaemia among sulphonylurea users: Population-based cohort study.

Aim: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas.

Materials And Methods: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020).

Effectiveness and safety of direct oral anticoagulants among patients with non-valvular atrial fibrillation and liver disease: A multinational cohort study.

Background And Aims: The effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population.

Methods: We assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020.

Kidney function estimators for drug dose adjustment of direct oral anticoagulants in older adults with atrial fibrillation.

Background: The Cockcroft-Gault equation (CrCl) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF).

Methods: Participants of the Berlin Initiative Study with AF and treated with DOACs were included.

Incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta-analysis of observational studies.

Aim: The results from the SUSTAIN-6 trial generated some uncertainty regarding the association between incretin-based drugs [dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)] and the risk of diabetic retinopathy. Our objective was to synthesize the available evidence from observational studies regarding the use of incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes.

Materials And Methods: We systemically searched Cochrane Library, Embase and Medline to identify observational studies of interest.

Pharmacologic Heterogeneity and Risk of Severe Hypoglycemia with Concomitant Use of Sulfonylureas and DPP-4 Inhibitors: Population-Based Cohort Study.

Dipeptidyl peptidase-4 inhibitors (DPP-4i) interact with sulfonylureas to increase their risk of hypoglycemia. Our population-based study assessed whether intraclass pharmacologic heterogeneity among sulfonylureas (long- vs. short-acting) and DPP-4i (peptidomimetic vs.

Considerations on the use of different comparators in pharmacovigilance: A methodological review.

Pharmacovigilance studies based on spontaneous reporting systems use disproportionality analysis methods to identify drug-event combinations with higher-than-expected reporting. Enhanced reporting is deemed as a proxy for a detected signal and is used to generate drug safety hypotheses, which can then be tested in pharmacoepidemiologic studies or randomized controlled trials. Higher-than-expected reporting means that the reporting rate of a drug-event combination of interest is disproportionately higher than the rate in a specific comparator or reference set.

Use of a Statistical Adaptive Treatment Strategy Approach for Emulating Randomized Controlled Trials Using Observational Data: The Example of Blood-Pressure Control Strategies for the Prevention of Cardiovascular Events Among Individuals With Hypertension at High Cardiovascular Risk.

Statistical approaches to adaptive treatment strategies (ATS) can be used to mimic the sequential decision-making inherently found in clinical practice. To illustrate the use of a statistical ATS approach, we emulated a target trial of different blood pressure (BP) control plans for the prevention of cardiovascular events among individuals with hypertension at high cardiovascular risk, inspired by the Systolic Blood Pressure Intervention Trial (SPRINT). We included 103,708 patients with hypertension and a "QRISK3" estimated 10-year risk of cardiovascular disease of ≥20% who initiated an antihypertensive drug between 1998 and 2018.

Concomitant use of statins and sodium-glucose co-transporter 2 inhibitors and the risk of myotoxicity reporting: A disproportionality analysis.

Aims: Recent case reports have suggested that sodium-glucose co-transporter 2 (SGLT2) inhibitors may interact with statins to increase their risk of myotoxicity. We assessed the risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins.

Methods: We queried the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2013 to 2021 for reports including SGLT2 inhibitors, statins or both.

Sulphonylureas versus metformin and the risk of ventricular arrhythmias among people with type 2 diabetes: A population-based cohort study.

Aim: To determine whether the use of sulphonylurea monotherapy, compared with metformin monotherapy, is associated with an increased risk of ventricular arrhythmia (VA) among patients initiating pharmacotherapy for type 2 diabetes.

Research Design And Methods: We conducted a population-based cohort study using electronic health data extracted from the UK's Clinical Practice Research Datalink Aurum. Using the active comparator, new-user cohort design, we compared rates of VA among patients aged 18 years or older using sulphonylurea monotherapy with those using metformin monotherapy as their initial pharmacological treatment for type 2 diabetes from April 1998 to December 2019.

Common Vaccines and the Risk of Incident Dementia: A Population-based Cohort Study.

Background: Observational studies suggesting that immunizations strongly decrease the risk of dementia had several methodological limitations. We assessed whether common vaccines are associated with the risk of dementia.

Methods: We assembled a population-based cohort of dementia-free individuals aged ≥50 years in the United Kingdom's Clinical Practice Research Datalink between 1988 and 2018.

Concomitant Use of Sulfonylureas and β-Blockers and the Risk of Severe Hypoglycemia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study.

Objective: The hypoglycemic potential of β-blockers among users of sulfonylureas, drugs that strongly increase the risk of this potentially fatal adverse effect, is not well understood. Our population-based cohort study assessed the potential association between concomitant use of sulfonylureas and β-blockers versus use of sulfonylureas alone and the risk of severe hypoglycemia.

Research Design And Methods: Using the U.

Challenges in evaluating treatments for COVID-19: The case of in-hospital anticoagulant use and the risk of adverse outcomes.

Anticoagulants are a potential treatment for the thrombotic complications resulting from COVID-19. We aimed to determine the association between anticoagulant use and adverse outcomes among hospitalized patients with COVID-19. We used data from the COVID-19 International Collaborative Research Project in South Korea from January to June 2020.

Obesity as a modifier of the cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes.

Aims: To assess the association between the use of sodium-glucose cotransporter-2 (SGLT2i) and cardiovascular outcomes and death as a function of obesity among patients with type 2 diabetes.

Methods: This new-user, active-comparator cohort study used U.K.

Effectiveness and Safety of Direct Oral Anticoagulants Among Octogenarians with Venous Thromboembolism: An International Multidatabase Cohort Study.

Background: The effects of direct oral anticoagulants (DOACs) among octogenarian patients with venous thromboembolism remains poorly understood. To address this knowledge gap, our study aimed to assess the effectiveness and safety of DOACs compared to vitamin K antagonists (VKAs) among octogenarians with venous thromboembolism.

Methods: We conducted an international cohort study using administrative health care databases from Québec, Canada, and Germany.

Bleeding in women with venous thromboembolism during pregnancy: A systematic review of the literature.

Objectives: Venous thromboembolism (VTE) represents an important cause of maternal morbidity and mortality. Estimates of bleeding associated with therapeutic-dose anticoagulation are variable. We describe the frequency of bleeding in pregnant women receiving therapeutic anticoagulation for VTE by means of a systematic review of the literature.