Pharmacoepidemiology and Drug Safety最新文献

{"title":"Use of Machine Learning to Compare Disease Risk Scores and Propensity Scores Across Complex Confounding Scenarios: A Simulation Study.","authors":"Yuchen Guo, Victoria Y Strauss, Sara Khalid, Daniel Prieto-Alhambra","doi":"10.1002/pds.70165","DOIUrl":"10.1002/pds.70165","url":null,"abstract":"<p><strong>Purpose: </strong>The surge of treatments for COVID-19 in the second quarter of 2020 had a low prevalence of treatment and high outcome risk. Motivated by that, we conducted a simulation study comparing disease risk scores (DRS) and propensity scores (PS) using a range of scenarios with different treatment prevalences and outcome risks.</p><p><strong>Method: </strong>Four methods were used to estimate PS and DRS: logistic regression (reference method), least absolute shrinkage and selection operator (LASSO), multilayer perceptron (MLP), and XgBoost. Monte Carlo simulations generated data across 25 scenarios varying in treatment prevalence, outcome risk, data complexity, and sample size. Average treatment effects were calculated after matching. Relative bias and average absolute standardized mean difference (ASMD) were reported.</p><p><strong>Result: </strong>Estimation bias increased as treatment prevalence decreased. DRS showed lower bias than PS when treatment prevalence was below 0.1, especially in nonlinear data. However, DRS did not outperform PS in linear or small sample data. PS had comparable or lower bias than DRS when treatment prevalence was 0.1-0.5. Three machine learning (ML) methods performed similarly, with LASSO and XgBoost outperforming the reference method in some nonlinear scenarios. ASMD results indicated that DRS was less impacted by decreasing treatment prevalence compared to PS.</p><p><strong>Conclusion: </strong>Under nonlinear data, DRS reduced bias compared to PS in scenarios with low treatment prevalence, while PS was preferable for data with treatment prevalence greater than 0.1, regardless of the outcome risk. ML methods can outperform the logistic regression method for PS and DRS estimation. Both decreasing sample size and adding nonlinearity and nonadditivity in data increased bias for all methods tested.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70165"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Trend in Selective Cyclooxygenase-2 Inhibitors Sales in Brazilian Drugstores.","authors":"Tayanny Margarida Menezes Almeida Biase, Marcus Tolentino Silva, Larissa Lopes, Taís Freire Galvao","doi":"10.1002/pds.70168","DOIUrl":"10.1002/pds.70168","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the trends in selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) sales in Brazil from 2014 to 2021.</p><p><strong>Methods: </strong>A time trend analysis of coxibs sales in Brazil from January 2014 to December 2021 was conducted using the Brazilian National Controlled Products Management System. Primary outcomes consisted of coxibs sales in defined daily dose (DDD) and DDD per 1000 inhabitants per day (DID), analyzed by Brazilian region (North, Northeast, South, Southeast, and Midwest). The trends in coxib consumption were analyzed using a segmented regression model, and the average annual percent change (AAPC) with a 95% confidence interval (95% CI) was calculated.</p><p><strong>Results: </strong>Celecoxib and etoricoxib sales increased in Brazil from 2014 to 2021. Celecoxib sales rose from 0.2 to 0.4 DID (AAPC 15.0; 95% CI 8.9, 21.5), particularly in the South, from 0.4 in 2014 to 0.7 DID in 2021 (AAPC 11.8; 95% CI 6.9, 16.9). Etoricoxib sales increased from 0.1 to 0.2, especially in the Midwest (AAPC 10.6; 95% CI 5.5, 16.0). Northern Brazil presented the lowest coxibs' consumption, which also increased in the period. National changes in etoricoxib sales were observed between 2014 and 2018 (annual percent change, APC 12.2; 95% CI -2.0, 28.4) and 2018 and 2021 (APC -3.6; 95% CI -22.1, 19.3).</p><p><strong>Conclusion: </strong>Coxibs sales in Brazil increased from 2014 to 2021, and celecoxib was the most used coxib. Shift changes in sales were observed in some regions for both coxibs, and nationally for etoricoxib. Prescription retention requirements for coxibs sales, instituted a decade before this analysis, potentially did not reduce consumption.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70168"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimation of the Duration of Antihypertensive Prescriptions: Validation of a Data-Driven Approach Using Rotterdam Study Data.","authors":"Chau L B Ho, David Youens, Walter P Abhayaratna, Max K Bulsara, Jeff Hughes, Rachael Moorin, Sallie-Anne Pearson, David B Preen, Christopher M Reid, Rikje Ruiter, Christobel M Saunders, Bruno H Stricker, John Stubbs, Frank J A van Rooij, Cameron Wright, Ninh Thi Ha","doi":"10.1002/pds.70164","DOIUrl":"10.1002/pds.70164","url":null,"abstract":"<p><strong>Objectives: </strong>Administrative medicine dispensing data often omit prescribed duration, which is important for research on adherence or other pharmacoepidemiological topics. While the reverse waiting time distribution (rWTD) method has been widely used to estimate prescribed durations, its accuracy in real-world dispensing data is unknown. We assessed the performance of the rWTD method against the actual prescribed duration recorded in the Rotterdam Study.</p><p><strong>Methods: </strong>100 725 antihypertensive (AHT) prescriptions from 2018 to 2019 were extracted from the Rotterdam Study's medicine data. Data were constructed into five scenarios with increasing variability in the number of medicines included and variations in prescribed duration. The rWTD with 10 random index dates with or without adjustment for the quantity of dispensed medicine was conducted in all scenarios. Relative differences and limit of agreement ratio based on Bland-Altman analysis were used to examine agreement between estimated and actual prescribed durations.</p><p><strong>Results: </strong>rWTD models without adjustment for the quantity of dispensed medicine performed well only in the most homogenous scenario. In scenarios with greater data variability, performance improved significantly when adjusted for the quantity of dispensed medicine. Relative difference decreased from ≥ 65% in models without covariates to ≤ 20% with covariates, and the limit of agreement ratio decreased from ≥ 36.8 in models without covariates to ≤ 5.3 with covariates. Stratification analysis by subclass of the AHT medicines provided similar results.</p><p><strong>Conclusions: </strong>The study demonstrated that as data variability increased, the accuracy of the rWTD estimations decreased. However, the rWTD can produce good estimates (relative difference from 0% to 28%) of prescribed duration for AHT medicines, with the highest accuracy in the model adjusting for the quantity of dispensed medicine or stratification of the data with a relative difference less than 20% and the limit of agreement ratio less than 5.3 for the estimation at the 90th percentile of inter-arrival density. Since this validation was limited to antihypertensive medicines, generalizing the finding to other chronic-use medicines should be undertaken with caution.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70164"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Hospital Discharge Prescription of Drugs That May Raise Blood Pressure in Patients With Hypertension\".","authors":"","doi":"10.1002/pds.70171","DOIUrl":"https://doi.org/10.1002/pds.70171","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70171"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"An Open-Source Implementation of Tree-Based Scan Statistics\".","authors":"","doi":"10.1002/pds.70167","DOIUrl":"https://doi.org/10.1002/pds.70167","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70167"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Adapting the European Concerted Action on Congenital Anomalies and Twins (EUROCAT) Guide 1.5 for Use in Post-Authorisation Safety Studies Using US Data\".","authors":"","doi":"10.1002/pds.70170","DOIUrl":"https://doi.org/10.1002/pds.70170","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70170"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarithromycin Versus Azithromycin for Community-Acquired Pneumonia and the Risk of Major Adverse Cardiovascular Events: A Multicentre Cohort Study Using Data From Canada and Denmark.","authors":"Theis Skovsgaard Itenov, Anthony D Bai, Tor Biering-Sørensen, Amol Verma, Fahad Razak, Ajay Bhasin, Henning Bundgaard, Pradeesh Sivapalan, Kasper Iversen, Christian Rasmussen, Jens Rasmussen, Lotte Klitfod, Kathrine Dircks, Jens-Ulrik S Jensen, Mike Fralick","doi":"10.1002/pds.70163","DOIUrl":"10.1002/pds.70163","url":null,"abstract":"<p><strong>Background: </strong>Studies suggest that clarithromycin is associated with an increased risk of major adverse cardiovascular events (MACE) among adults with coronary artery disease. However, data comparing clarithromycin to other macrolides, such as azithromycin, in a broader population are lacking.</p><p><strong>Methods: </strong>A multicenter study was conducted in 33 hospitals in Ontario, Canada, and Copenhagen, Denmark, using the Target Trial framework. Adults hospitalized with community-acquired pneumonia (CAP) who received either clarithromycin or azithromycin were included. The primary outcome was MACE, defined as the one-year risk of nonfatal myocardial infarction, nonfatal stroke, or all-cause mortality. Propensity score matching and Cox proportional hazards models were used for analysis.</p><p><strong>Results: </strong>In Ontario, we identified 23 081 patients with CAP, and 11 164 received oral macrolides. After propensity score matching, the primary outcome occurred in 7.8% of clarithromycin patients and 9.1% of azithromycin patients (HR 0.85, 95% CI 0.60-1.21). In Copenhagen, there were 11 280 patients with CAP and 3924 received oral macrolides. After propensity score matching, 19% of clarithromycin patients and 12% of azithromycin patients experienced the primary outcome for oral macrolides (HR 1.7, 95% CI 1.2-2.4, p = 0.002). Meta-analysis of the point estimate from each country provided an overall HR of 1.21 (95% CI 0.61-2.39). For intravenous macrolides in Copenhagen, the HR was 1.15 (95% CI 1.0-1.3, p = 0.007) for clarithromycin compared to azithromycin.</p><p><strong>Conclusion: </strong>This study did not consistently observe an increased risk of cardiovascular events with clarithromycin among adults hospitalized with CAP. However, the observational nature of the study may introduce selection bias and unmeasured confounding.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70163"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"A Brief Report on Proposed Areas of International Harmonization of Real-World Evidence Relevance, Reliability and Quality Standards Among Medical Product Regulators\".","authors":"","doi":"10.1002/pds.70169","DOIUrl":"https://doi.org/10.1002/pds.70169","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 6","pages":"e70169"},"PeriodicalIF":2.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Interactions With Tamoxifen and Treatment Effectiveness in Premenopausal Breast Cancer Patients: A Bayesian Joint Modeling Approach.","authors":"Kirsten M Woolpert, Deirdre P Cronin-Fenton, Per Damkier, Anders Kjærsgaard, Stephen Hamilton-Dutoit, Bent Ejlertsen, Richard F MacLehose, Peer Christiansen, Rebecca A Silliman, Timothy L Lash, Thomas P Ahern, Lindsay J Collin","doi":"10.1002/pds.70157","DOIUrl":"10.1002/pds.70157","url":null,"abstract":"<p><strong>Purpose: </strong>Tamoxifen is guideline treatment for premenopausal women with estrogen receptor-positive (ER+) breast cancer. Therapeutic efficacy relies partly on tamoxifen biotransformation by CYP2D6, CYP2C19, and CYP3A4 enzymes. We conducted a cohort study to evaluate whether concomitant prescription of drugs that inhibit these enzymes impacted breast cancer recurrence.</p><p><strong>Methods: </strong>We enrolled 4493 premenopausal women with stage I-III ER+ breast cancer (2002-2011) treated with tamoxifen. We defined time-varying CYP-inhibiting drug exposures as the proportion of overlapping days during the tamoxifen treatment period. We estimated associations of concomitant medication use with recurrence using: (1) Bayesian joint modeling (hazard ratio [HR] and 95% credible intervals [95% CrI]), (2) traditional Cox regression (HR and 95% confidence intervals [95% CI]).</p><p><strong>Results: </strong>During tamoxifen therapy, 13% of the cohort used strong CYP2D6 inhibitors, 31% weak CYP2D6 inhibitors, 37% CYP2C19 inhibitors, and 12% CYP3A4/5 inhibitors. Bayesian joint models showed that women with ≥ 50% overlap between tamoxifen and CYP2D6 inhibitors had increased recurrence risk compared with 0% overlap (HR: 1.24, 95% CrI: 0.96, 1.58). No recurrence association was seen for CYP2C19 inhibitors (≥ 50% vs. 0%, HR = 1.0, 95% CrI: 0.69, 1.40), but traditional Cox models yielded positive associations for CYP2C19 overlap (≥ 50% vs. 0%, HR = 1.45, 95% CI: 1.07, 1.96). With Bayesian joint models, we observed no association between ≥ 50% versus 0% overlap with CYP3A4/5 inhibitors (HR: 0.84, 95% CrI: 0.32, 1.93).</p><p><strong>Conclusions: </strong>With Bayesian joint modeling, we saw a slight increase in recurrence among CYP2D6-inhibitor users, but no increase among CYP2C19- or CYP3A4-inhibitor users. Results from Cox regression models were less plausible.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 5","pages":"e70157"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hospital Discharge Prescription of Drugs That May Raise Blood Pressure in Patients With Hypertension.","authors":"Sarasa Miyake, Atsushi Miyawaki, Hiroki Matsui, Yuya Kimura, Hideo Yasunaga","doi":"10.1002/pds.70150","DOIUrl":"10.1002/pds.70150","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to determine the frequency of discharge prescriptions of drugs that may raise blood pressure (BP) in hospitalized patients with hypertension and identify factors associated with these prescriptions.</p><p><strong>Methods: </strong>A retrospective cross-sectional analysis was conducted using a nationwide inpatient database in Japan, focusing on adults with hypertension discharged from acute care hospitals between April 2021 and March 2022. The primary outcome was the prescription of drugs that may raise BP at discharge. A multivariable linear probability model was employed to assess the relationship between patient and hospital characteristics and the likelihood of receiving these prescriptions.</p><p><strong>Results: </strong>Among 979 234 patients with hypertension (mean age: 75.3 years, standard deviation: 13.2), 230 792 (23.6%) received at least one drug that may elevate BP at discharge. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently prescribed (46.6%), followed by glucocorticoids (35.3%), atypical antipsychotics (15.1%), antidepressants (7.9%), and Japanese herbal medicines (6.1%). Prescription prevalence was higher among female patients, younger adults, those admitted for medical conditions, non-emergency hospitalizations, patients with disabilities, and those with a Charlson Comorbidity Index of 1. Patients hospitalized for musculoskeletal or skin conditions, transferred to another hospital, or discharged from high-volume hospitals were also more likely to receive these prescriptions.</p><p><strong>Conclusions: </strong>Drugs that may raise BP are commonly prescribed at discharge for patients with hypertension. This highlights the need for targeted interventions to optimize medication management at discharge, aiming to improve BP control and patient outcomes.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 5","pages":"e70150"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}