Joshua Gagne

Joshua Gagne
Brigham and Women's Hospital | BWH · Division of Pharmacoepidemiology and Pharmacoeconomics

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339
Publications
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Publications

Publications (339)
Article
Importance: Guidelines for managing venous thromboembolism (VTE) recommend at least 90 days of therapy with oral anticoagulants. Limited evidence exists about the optimal drug for continuing therapy beyond 90 days. Objective: To compare having prescriptions dispensed for apixaban, rivaroxaban, or warfarin after an initial 90 days of anticoagulat...
Article
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Importance Some selective serotonin reuptake inhibitors (SSRIs) inhibit the enzymes responsible for the metabolism of oxycodone, a potent prescription opioid. The clinical consequences of this interaction on the risk of opioid overdose have not been elucidated. Objective To compare opioid overdose rates in patients initiating oxycodone while takin...
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Purpose: The high-dimensional propensity score (HDPS) is a semi-automated procedure for confounder identification, prioritisation, and adjustment in large healthcare databases that requires investigators to specify data dimensions, prioritisation strategy, and tuning parameters. In practice, reporting of these decisions is inconsistent and this ca...
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The Sentinel System is a major component of the United States Food and Drug Administration’s (FDA) approach to active medical product safety surveillance. While Sentinel has historically relied on large quantities of health insurance claims data, leveraging longitudinal electronic health records (EHRs) that contain more detailed clinical informatio...
Chapter
This chapter provides an overview of how the field and its methods can contribute to these larger themes in medical care delivery and health services research, from the perspective of academia. Underuse of needed drugs by patients is one of the most common medication‐related problems, and one that can be readily identified by pharmacoepidemiology....
Article
Objective Medication nonadherence is linked to worsened clinical outcomes and increased costs. Existing system-level adherence interventions rely on insurer claims for patient identification and outcome measurement, yet suffer from incomplete capture and lags in data acquisition. Data from pharmacies regarding prescription filling, captured in reta...
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Electronic health records (EHR) discontinuity, i.e., receiving care outside of the study EHR system, can lead to information bias in EHR‐based real‐world evidence (RWE) studies. An algorithm has been previously developed to identify patients with high EHR‐continuity. We sought to assess whether applying this algorithm to patient selection for inclu...
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Background: The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear. Objective: To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels. Design: 1:1 propensity score-matched analysis of Medicare data, 2010 to 2017. Setting:...
Article
Drug manufacturers sometimes offer co-payment coupons to offset patient out-of-pocket costs. Although coupons can help patients afford necessary medications, they increase overall drug spending by encouraging use of expensive brand-name drugs over less expensive generics.¹,2 Coupons are prohibited by Medicare and Medicaid, but they are available fo...
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Importance Spending in Medicare Part D continues to increase. Yet, studies of Medicare Part D are plagued by a common limitation: none can fully account for confidential rebates and other discounts that drug manufacturers and pharmacies pay to Medicare Part D plans. Objectives To review existing methods and to propose an approach for estimating re...
Article
Polypharmacy is common among patients taking prescription opioids long‐term, and the co‐dispensing of interacting medications may further increase opioid overdose risk. To identify non‐opioid medications that may increase opioid overdose risk in this population, we conducted a case‐crossover‐based screening of electronic claims data from IBM® Marke...
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Background: Warfarin remains widely used and a key comparator in studies of other direct oral anticoagulants. As longer-than-needed warfarin prescriptions are often provided to allow for dosing adjustments according to International Normalized Ratios (INRs), the common practice of using a short allowable gap between dispensings to define warfarin...
Article
Introduction: Since 2007, the US Food and Drug Administration has had the authority to require risk evaluation and mitigation strategy (REMS) programs for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Such programs can include requirements for patient monitoring, restrictions on...
Article
Objectives In the United States, brand-name prescription drugs remain expensive until market exclusivity ends and lower-cost generics become available. Delayed generic drug uptake may increase spending and worsen medication adherence and patient outcomes. We assessed recent trends and factors associated with generic uptake. Methods Among 227 drugs...
Article
(Acta Obstet Gynecol Scand. 2020;99:399–405) Severe maternal morbidity associated with childbirth has increased in the last 30 years in the United States. A score to predict risk for maternal morbidity would be useful to help place high-risk women at better-equipped facilities and also address some confounding factors in research. The Obstetric Com...
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Purpose Consensus is needed on conceptual foundations, terminology and relationships among the various self‐controlled “trigger” study designs that control for time‐invariant confounding factors and target the association between transient exposures (potential triggers) and abrupt outcomes. The International Society for Pharmacoepidemiology (ISPE)...
Article
Tree-based scan statistics (TreeScan) are a data-mining method that adjusts for multiple testing of correlated hypotheses when screening thousands of potential adverse events for signal identification. Simulation has demonstrated the promise of TreeScan with a propensity score (PS) matched cohort design. However, it is unclear which variables to in...
Article
Background: In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence. Methods: Using a national claims database of commercially-insured patients, we performed a coho...
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Self-controlled designs, specifically the case-crossover (CCO) and the self-controlled case series (SCCS), are increasingly utilized to generate real-world evidence (RWE) on drug-drug interactions (DDIs). While these designs share the advantages and limitations of within-individual comparison, they also have design-specific assumptions. It is not k...
Article
IntroductionRisk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal.Objective We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoet...
Article
Purposes Drug induced acute liver injury (ALI) is a frequent cause of liver failure. Case‐based designs were empirically assessed and calibrated in the French National claims database (SNDS), aiming to identify the optimum design for drug safety alert generation associated with ALI. Methods All cases of ALI were extracted from SNDS (2009‐2014) usi...
Article
Background: We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for renal cell carcinoma. Methods: Using Danish health registries, we conducted a nest...
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We use simulated data to examine the consequences of depletion of susceptibles for hazard ratio (HR) estimators based on a propensity score (PS). First, we show that the depletion of susceptibles attenuates marginal HRs toward the null by amounts that increase with the incidence of the outcome, the variance of susceptibility, and the impact of susc...
Article
Objective There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to nAMD. If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data...
Article
Objectives: To better understand patients' and pharmacists' preferences for and experiences with changes in pill appearance (size, shape, color, and markings). Study design: Cross-sectional. Methods: We conducted independent national surveys of patients 50 years and older taking generic drugs for depression, diabetes, epilepsy, HIV, hyperlipid...
Article
Using nationwide Danish registries, we conducted a population-based case-crossover study evaluating the association between switching from a vitamin K antagonist (VKA) to a direct oral anticoagulant (DOAC), and vice-versa, and 30-day risks of bleeding and arterial thromboembolism in atrial fibrillation (AF) patients. The case-crossover population w...
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Sulfonylureas are commonly used to treat type 2 diabetes mellitus. Despite awareness of their effects on cardiac physiology, a knowledge gap exists regarding their effects on cardiovascular events in real-world populations. Prior studies reported sulfonylurea-associated cardiovascular death but not serious arrhythmogenic endpoints like sudden cardi...
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Purpose The case‐crossover design is increasingly used to evaluate the effects of chronic medications; however, as traditionally implemented in pharmacoepidemiology, with referent period preceding the outcome, it may lead to bias in the presence of persistent exposures. We aimed to evaluate the extent and magnitude of bias in case‐crossover analyse...
Article
(Am J Obstet Gynecol. 2019;221:271.e1–271.e10) An important strategy for improving maternal health is development of a tool that reliably identifies women at risk of severe maternal morbidity (SMM) and death. The obstetric comorbidity index (OB-CMI) summarizes the burden of maternal comorbidities and allows for the generation of a single numeric sc...
Article
Background Less than half of patients with cardiometabolic disease consistently take prescribed medications. While health insurers and some delivery organizations use claims to measure adherence, most clinicians do not have access during routine interactions. Self-reported scales exist, but their practical utility is often limited by length or cost...
Article
Despite reductions in opioid prescribing in the US in recent years,¹ rates of drug overdose deaths continue to increase.² While most of these deaths involve opioids, significant increases in overdose deaths involving other prescription drugs, including stimulants, benzodiazepines, and depressants, have been reported.³ Yet, relatively little is know...
Preprint
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Objective Using US claims data and the most up-to-date pharmacoepidemiological study design tools we aimed to investigate two safety signals for (1) macrolides and heart failure; and (2) non-steroidal anti-inflammatory drugs (NSAIDs) and pneumonia generated from a large-scale screening analysis using a self-controlled sequence symmetry design in Da...
Article
IntroductionClinical practice guidelines recommend co-prescribing naloxone to patients at high risk of opioid overdose, but few such patients receive naloxone. High costs of naloxone may contribute to limited dispensing.Objective The aim of this study was to evaluate rates and costs of dispensing naloxone to patients receiving opioid prescriptions...
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Background: Apixaban and rivaroxaban are the most commonly prescribed direct oral anticoagulants for adults with atrial fibrillation, but head-to-head data comparing their safety and effectiveness are lacking. Objective: To compare the safety and effectiveness of apixaban versus rivaroxaban for patients with nonvalvular atrial fibrillation. Des...
Article
Objectives: To introduce the methodology of the ALCAPONE project. Background: The French National Healthcare System Database (SNDS), covering 99% of the French population, provides a potentially valuable opportunity for drug safety alert generation. ALCAPONE aimed to assess empirically in the SNDS case-based designs for alert generation related...
Article
Objectives Outcomes-based contracts tie rebates and discounts for expensive drugs to outcomes. The objective was to estimate the utility of outcomes-based contracts for diabetes medications using real-world data and to identify methodologic limitations of this approach. Methods A population-based cohort study of adults newly prescribed a medicatio...
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Background: The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic e...
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Purpose: When investigators have two claims-based definitions for a binary confounder, it is unclear whether to prefer the more sensitive or more specific definition. Our objective was to compare adjusting for the sensitive or specific definition alone vs two novel approaches combining both definitions: a "two-algorithm indicator" and a "two-algor...
Article
Angiotensin receptor blockers (ARBs) are one of the most common prescription drug classes, used by 5.8% of adults in the United States in 2011-2012 for treatment of hypertension, heart failure, and diabetic nephropathy.¹ Discovery of potentially carcinogenic nitrosamine impurities (N-nitrosodimethylamine, N-nitroso-N-diethylamine, and N-nitroso-N-m...
Article
Sequential analysis is used in clinical trials and postmarket drug safety surveillance to prospectively monitor efficacy and safety to quickly detect benefits and problems, while taking the multiple testing of repeated analyses into account. When there are multiple outcomes, each one may be given a weight corresponding to its severity. This paper i...
Chapter
Once a small, arcane discipline at the fringes of both epidemiology and pharmacology, pharmacoepidemiology has emerged as a central discipline for the healthcare delivery system and in academic medical centers. As records of healthcare interactions and transactions are increasingly captured digitally, pharmacoepidemiology has become a key tool for...
Chapter
A distributed data network architecture allows sensitive individual‐level and institution‐level information to be stored locally under the direct control of participating data partners. It enables multidatabase comparative safety and effectiveness studies of rare exposures, rare outcomes, or specific patient populations, while providing strong prot...
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Background: Self-controlled designs, both case–crossover and self-controlled case series, are well suited for evaluating outcomes of drug–drug interactions in electronic healthcare data. Their comparative performance in this context, however, is unknown. Methods: We simulated cohorts of patients exposed to two drugs: a chronic drug (object) and a s...
Article
Introduction: A previously developed Obstetric Comorbidity Index has been validated in highly selected cohorts. Validation of the index in an unselected population as well as in other health registers is, however, of high importance to determine external validity. Material and methods: Using nationwide registers, we formed a nationwide cohort in...
Chapter
A drug–drug interaction (DDI) occurs when one or more drugs affect the pharmacokinetics and/or pharmacodynamics of one or more other drugs. Pharmacoepidemiology studies are the principal way of studying the health effects of potential DDIs. A number of methodologic problems are more prominent in pharmacoepidemiologic studies of DDIs than in those e...
Article
Objectives Inappropriate use of the case-crossover design, which is efficient for examining associations between brief exposure and abrupt outcomes, in evaluating the effects of medications in the presence of exposure-time trends or persistent drug use may generate spurious associations. We compared different approaches to adjusting for these sourc...
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Estimating hazard ratios (HR) presents challenges for time-to-event analyses of cohorts with differential depletion of susceptibles. When the treatment effect is not null, cohorts that were balanced at baseline tend to become unbalanced on baseline characteristics over time as 'susceptible' individuals drop out of the population at risk differentia...
Article
Research that makes secondary use of administrative and clinical healthcare databases is increasingly influential for regulatory, reimbursement, and other healthcare decision-making. Consequently, there are numerous guidance documents on reporting for studies that use ‘real-world’ data captured in administrative claims and electronic health record...
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Introduction Patients taking non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, and apixaban have reported experiencing angioedema in randomized trials and routine care. Objective The aim of this study was to quantify the association between NOACs and angioedema relative to warfarin among routinely treated patien...
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Purpose: Little is known about how disease risk score (DRS) development should proceed under different pharmacoepidemiologic follow-up strategies. In an analysis of dabigatran vs. warfarin and risk of major bleeding, we compared the results of DRS adjustment when models were developed under "intention-to-treat" (ITT) and "as-treated" (AT) approach...
Article
Purpose: As more biosimilars become available in the United States, postapproval noninterventional studies describing biosimilar switching and comparing effectiveness and/or safety between switchers and nonswitchers will play a key role in generating real-world evidence to inform clinical practices and policy decisions. Ensuring sound methodology...
Article
Importance: Prescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk, individuals may still access prescription opioids dispensed to family members. Objective: To determine whether opioid prescriptions to family members were associated wit...
Article
Background: The obstetric comorbidity index summarizes the burden of maternal comorbidities into a single number and holds promise as a maternal risk-assessment tool. Objective: The aim of this study was to assess the clinical performance of this comorbidity-based screening tool to accurately identify women on labor and delivery who are at risk...
Article
To the Editor We write to explain some errors that occurred in our Research Letter, “Trends in Opioid Prescription in Children and Adolescents in a Commercially Insured Population in the United States, 2004-2017,”¹ that was published online on November 12, 2018, and in the January 2019 issue of JAMA Pediatrics. We had evaluated trends in opioid pre...
Article
Introduction While medical chart review remains the gold standard to validate health conditions or events identified in administrative claims and electronic health record databases, it is time consuming, expensive and can involve subjective decisions. Aim The aim of this study was to describe the landscape of technology-enhanced approaches that co...
Article
Importance There is a need for better understanding of the comparative safety of systemic medications used in the treatment of psoriasis. Objective To compare the risk of serious infection associated with biologic and nonbiologic systemic medications in patients with psoriasis. Design, Setting, and Participants An observational cohort study was c...
Article
We sought to refine understanding about associations identified in prior studies between angiotensin‐II receptor blockers, metformin, selective serotonin reuptake inhibitors, fibric‐acid derivatives, or calcium channel blockers and progression to glaucoma filtration surgery for open angle glaucoma (OAG). We used new‐initiator, active‐comparator coh...
Article
Purpose Bootstrapping can account for uncertainty in propensity score (PS) estimation and matching processes in 1:1 PS‐matched cohort studies. While theory suggests that the classical bootstrap can fail to produce proper coverage, practical impact of this theoretical limitation in settings typical to pharmacoepidemiology is not well studied. Metho...
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Background To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but a...
Data
Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing clinical outcomes for patients initiating authorized generics (AGs) versus generics and patients switching from brand-name to AGs versus generics before 1:1 propensity score matching in each database. The clinical outcome for amlodipine tablets, amlodipine-benazepril capsules, and qui...
Data
Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing clinical outcomes for authorized generic (AG) versus brand initiators and generic versus brand initiators before 1:1 propensity score matching in each database. The outcome for amlodipine tablets, amlodipine-benazepril capsules, and quinapril tablets was a composite endpoint comprisin...
Data
Prospective analysis plan. Funding proposal submitted to the US Food and Drug Administration. (PDF)
Data
Strengthening the reporting of observational studies in epidemiology (STROBE) checklist. (PDF)
Article
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Background: The case-crossover design may be useful for evaluating the clinical impact of drug-drug interactions in electronic healthcare data; however, experience with the design in this context is limited. Methods: Using US healthcare claims data (1994-2013), we evaluated two examples of interacting drugs with prior evidence of harm: (1) cytoc...
Article
Purpose The U.S. Food and Drug Administration's Sentinel Initiative “modular programs” have been shown to replicate findings from conventional protocol‐driven, custom‐programmed studies. One such parallel assessment—dabigatran and warfarin and selected outcomes—produced concordant findings for three of four study outcomes. The effect estimates and...
Article
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Purpose Implementing a cohort study in longitudinal healthcare databases requires looking back over some covariate assessment period (CAP) preceding cohort entry to measure confounders. We used simulations to compare fixed‐duration versus all‐available CAPs for confounder adjustment in the presence of differences in available baseline time between...
Article
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During 2017, opioids were associated with 47,600 deaths in the United States, approximately one third of which involved a prescription opioid (1). A