Pharmacoepidemiology and Drug Safety最新文献

{"title":"Impact of Regulatory Interventions on Ulipristal Acetate 5 mg (Esmya) Use in Spain: An Interrupted Time‐Series Analysis","authors":"Marta Monreal‐Di Bello, Diana González‐Bermejo, Belén Castillo‐Cano, Alfonso Rodriguez‐Pascual, Dolores Montero‐Corominas","doi":"10.1002/pds.70004","DOIUrl":"https://doi.org/10.1002/pds.70004","url":null,"abstract":"PurposeSince late 2017, the use of ulipristal acetate 5 mg (UPA; Proprietary name: Esmya) has been under review in the European Union, due to an emerging hepatic risk. In February 2018 and in July 2018, the Spanish Agency of Medicines and Medical Devices and the marketing authorization holder put two risk minimization measures (RMM) in place, in order to inform about new safety information and to mitigate this risk. This study aims to assess RMM effectiveness in Spain, by performing an interrupted time‐series (ITS) analyses, between 2014 and 2019.MethodTwo quasi‐experimental ITS analyses to examine the use of UPA before and after the RMM release were performed: (a) an ecological study using aggregated data from a drug consumption database; and (b) a study using primary healthcare data gathered from electronic clinical records.ResultsRegulatory interventions were associated with an immediate and significant decrease level of DID (the number of DDD dispensed per 100 000 inhabitants and day) and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. However, a change in the slope was not observed and the use started rising again in the last segment of the study period.ConclusionDespite RMM had an immediate strong impact on UPA use, the last segment upward trend in the long‐term might have been affected by the lack of comparable therapeutic alternatives. Further studies should be performed to confirm the increase trend observed and analyze subsequent measures and additional data.","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"18 1","pages":"e70004"},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255609","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":"Exposure to Valsartan Products Containing Nitrosamine Impurities in the United States, Canada, and Denmark","authors":"Efe Eworuke, Mayura U. Shinde, Laura Hou, J. Michael Paterson, Peter Bjødstrup Jensen, Judith C. Maro, Ashish Rai, Anton Pottegård, Daniel Scarnecchia, Yuanling Liang, Deborah Johnson, Robert W. Platt, Hana Lee, Marie C. Bradley","doi":"10.1002/pds.5849","DOIUrl":"https://doi.org/10.1002/pds.5849","url":null,"abstract":"BackgroundFollowing the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the United States, Canada, and Denmark.MethodsWe conducted a retrospective cohort study using administrative healthcare data from the US FDA Sentinel System, four Canadian provinces that contribute to the Canadian Network for Observational Drug Effect Studies (CNODES), and the Danish National Prescription Registry. Patients, 18 years and older between May 2012 and December 2020 with a valsartan dispensing were identified in each database. Patients were followed from the date of valsartan dispensing until discontinuation. We defined four valsartan exposure categories based on nitrosamine impurity status; recalled generic products with confirmed NDMA/NDEA levels (recalled‐tested); recalled generic products that were not tested (recalled); non‐recalled generic and non‐recalled branded products. In Denmark, the recalled‐tested category was not included due to absence of testing data. The proportion and duration of use of valsartan episodes stratified by nitrosamine‐impurity status was calculated.ResultsWe identified 3.3 and 2.8 million (United States) and 51.3 and 229 thousand (Canada) recalled‐tested and recalled valsartan exposures. In Denmark, where valsartan exposure was generally low, there were 10 747 recalled exposures. Immediately after the recall notices were issued, there was increased rates of switching to a non‐valsartan ARB. The mean duration of use of the recalled‐tested products was 167 (±223.1) and 146 (±255.8) days in the United States and Canada respectively. For the recalled products, mean cumulative duration of use was 178 (±249.6), 269 (±397.3) and 166 (±251.0) days in the United States, Canada, and Denmark, respectively.ConclusionIn this cohort study, despite widespread use of recalled generic valsartan between 2012 and 2018, the duration of use was relatively short and probably did not pose an elevated risk of nitrosamine‐induced cancer. However, since products with nitrosamine impurity could have been on the market over a 6‐year period, patients exposed to these products for longer durations could have a potentially different risk of cancer.","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"502 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255608","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":"An Emulated Target Trial Case Study of Real‐World Overall Survival With Second‐Line Maintenance Niraparib Versus Active Surveillance in Patients With Recurrent Ovarian Cancer","authors":"Jessica A. Perhanidis, Linda Kalilani, Nicole M. Zimmerman, Amanda Golembesky","doi":"10.1002/pds.70001","DOIUrl":"https://doi.org/10.1002/pds.70001","url":null,"abstract":"PurposeThis retrospective real‐world study compared overall survival (OS) between patients with <jats:italic>BRCA</jats:italic> wild‐type (<jats:italic>BRCA</jats:italic>wt) recurrent epithelial ovarian cancer (OC) who received niraparib second‐line maintenance (2LM) versus active surveillance (AS) using target trial emulation, cloning, inverse probability of censoring weighting (IPCW) methodology to minimize immortal time bias.MethodsEligible patients from a United States‐based, deidentified, electronic health record–derived database were diagnosed with epithelial OC (January 1, 2011–May 31, 2021), were <jats:italic>BRCA</jats:italic>wt, and completed second‐line (2L) therapy (January 1, 2017–March 2, 2022). Patient data were cloned at index (2L last treatment date), assigned to niraparib 2LM and AS cohorts, and censored when treatment deviated from clone assignment. Follow‐up was measured from index to earliest of study end (May 31, 2022), last activity, or death. Median OS (mOS) and hazard ratios were estimated from stabilized IPCW Kaplan–Meier curves and Cox regression models.ResultsOverall, 199 patients received niraparib 2LM, and 707 had their care managed with AS. Key characteristics were balanced across cohorts after cloning and stabilized IPCW. Median follow‐up was 15.6‐ and 9.3‐months pre‐cloning. IPCW mOS was 24.1 months (95% CI: 20.9–29.5) and 18.4 months (95% CI: 15.1–22.8) in niraparib 2LM and AS cohorts, respectively (hazard ratio, 0.77; 95% CI: 0.66–0.89).ConclusionsThis real‐world study provides supportive evidence of an OS benefit for patients with <jats:italic>BRCA</jats:italic>wt recurrent OC who received 2LM niraparib monotherapy compared with those whose care was managed with AS. The analytic strategies implemented were useful in minimizing immortal time bias and measured confounding.","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"73 1","pages":"e70001"},"PeriodicalIF":2.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224438","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":"A Two‐Step Framework for Validating Causal Effect Estimates","authors":"Lingjie Shen, Erik Visser, Felice van Erning, Gijs Geleijnse, Maurits Kaptein","doi":"10.1002/pds.5873","DOIUrl":"https://doi.org/10.1002/pds.5873","url":null,"abstract":"Background: Comparing causal effect estimates obtained using observational data to those obtained from the gold standard (i.e., randomized controlled trials [RCTs]) helps assess the validity of these estimates. However, comparisons are challenging due to differences between observational data and RCT generated data. The unknown <jats:italic>treatment assignment</jats:italic> <jats:italic>mechanism</jats:italic> in the observational data and varying <jats:italic>sampling mechanisms</jats:italic> between the RCT and the observational data can lead to confounding and sampling bias, respectively.Aims: The objective of this study is to propose a two‐step framework to validate causal effect estimates obtained from observational data by adjusting for both mechanisms.Materials and Methods: An estimator of causal effects related to the two mechanisms is constructed. A two‐step framework for comparing causal effect estimates is derived from the estimator. An R package <jats:italic>RCTrep</jats:italic> is developed to implement the framework in practice.Results: A simulation study is conducted to show that using our framework observational data can produce causal effect estimates similar to those of an RCT. A real‐world application of the framework to validate treatment effects of adjuvant chemotherapy obtained from registry data is demonstrated.Conclusion: This study constructs a framework for comparing causal effect estimates between observational data and RCT data, facilitating the assessment of the validity of causal effect estimates obtained from observational data.","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 1","pages":"e5873"},"PeriodicalIF":2.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185366","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":"PMDA Perspective on RWD/RWE Utilization for Regulatory Purposes Including Assessment on the Impacts of Regulatory Actions and Safety Risk of a Drug at Postmarketing Stage.","authors":"Kazuhiro Kajiyama, Maki Komamine, Naoya Horiuchi, Toyotaka Iguchi, Yoshiaki Uyama","doi":"10.1002/pds.70007","DOIUrl":"10.1002/pds.70007","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"33 9","pages":"e70007"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140745","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":"Strengthening Real-World Evidence on Question Not Answered by Randomized Trials: A Trial Calibration Approach.","authors":"Julien Kirchgesner, Shirley V Wang, Sebastian Schneeweiss","doi":"10.1002/pds.70008","DOIUrl":"10.1002/pds.70008","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"33 9","pages":"e70008"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120386","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":"Sharing Is Caring? International Society for Pharmacoepidemiology Review and Recommendations for Sharing Programming Code.","authors":"John Tazare, Shirley V Wang, Rosa Gini, Daniel Prieto-Alhambra, Peter Arlett, Daniel R Morales Leaver, Caroline Morton, John Logie, Jennifer Popovic, Katherine Donegan, Sebastian Schneeweiss, Ian Douglas, Anna Schultze","doi":"10.1002/pds.5856","DOIUrl":"10.1002/pds.5856","url":null,"abstract":"<p><strong>Purpose: </strong>There is increasing recognition of the importance of transparency and reproducibility in scientific research. This study aimed to quantify the extent to which programming code is publicly shared in pharmacoepidemiology, and to develop a set of recommendations on this topic.</p><p><strong>Methods: </strong>We conducted a literature review identifying all studies published in Pharmacoepidemiology and Drug Safety (PDS) between 2017 and 2022. Data were extracted on the frequency and types of programming code shared, and other key open science practices (clinical codelist sharing, data sharing, study preregistration, and stated use of reporting guidelines and preprinting). We developed six recommendations for investigators who choose to share code and gathered feedback from members of the International Society for Pharmacoepidemiology (ISPE).</p><p><strong>Results: </strong>Programming code sharing by articles published in PDS ranged from 1.8% in 2017 to 9.5% in 2022. It was more prevalent among articles with a methodological focus, simulation studies, and papers which also shared record-level data.</p><p><strong>Conclusion: </strong>Programming code sharing is rare but increasing in pharmacoepidemiology studies published in PDS. We recommend improved reporting of whether code is shared and how available code can be accessed. When sharing programming code, we recommend the use of permanent digital identifiers, appropriate licenses, and, where possible, adherence to good software practices around the provision of metadata and documentation, computational reproducibility, and data privacy.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"33 9","pages":"e5856"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133417","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":"Re-Exposure to Culprit Medication Following Adverse Drug Event Diagnosis in Canadian Emergency Department Patients: A Cohort Study.","authors":"Maeve E Wickham, Kimberlyn M McGrail, Michael R Law, Amber Cragg, Corinne M Hohl","doi":"10.1002/pds.70012","DOIUrl":"10.1002/pds.70012","url":null,"abstract":"<p><strong>Purpose: </strong>The magnitude of repeat exposures to culprit medications after hospital discharge is not well studied. We combined prospective cohort data with administrative health data to understand the frequency of repeat exposures to culprit medications after discharge and the risk factors for their occurrence.</p><p><strong>Methods: </strong>This was a retrospective analysis of three prospective cohorts of patients who presented to the hospital with an adverse drug event in British Columbia, from 2008 to 2015 (n = 849). We linked prospectively identified adverse drug events to administrative data to examine patterns of redispensing of culprit medications. We used Cox regression to assess risk factors for re-exposure, and conducted subgroup analyses for essential vs. nonessential medications.</p><p><strong>Results: </strong>Among 849 diagnosed adverse drug events, 45.2% had subsequent culprit medication redispensing within a year of hospital discharge. The factors associated with re-exposures included atrial fibrillation, adverse drug event type (e.g. adverse reaction), culprit medication type, and longer historical duration of medication use.</p><p><strong>Conclusions: </strong>Re-exposures to culprit medications occurred in almost half of the adverse drug events diagnosed in emergency departments. Many of these were appropriate re-exposures to essential medications for indications in which the risk of uncontrolled disease likely outweighed the risk of a repeat adverse event. More research is needed to understand re-exposures to nonessential medications or medications with safer alternatives.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"33 9","pages":"e70012"},"PeriodicalIF":4.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292833","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":"Standardization of coding definitions for sickle cell disease complications: A systematic literature review.","authors":"Paulette Negron Ericksen, Firas Dabbous, Rajrupa Ghosh, Surbhi Shah, Xunming Sun, Emily Riehm Meier, Carmine Colavecchia","doi":"10.1002/pds.5769","DOIUrl":"10.1002/pds.5769","url":null,"abstract":"<p><strong>Purpose: </strong>Sickle cell disease (SCD) affects all organ systems and is characterized by numerous acute and chronic complications and comorbidities. Standardized codes are needed for complications/comorbidities used in real-world evidence (RWE) studies that rely on administrative and medical coding. This systematic literature review was conducted to produce a comprehensive list of complications/comorbidities associated with SCD, along with their diagnosis codes used in RWE studies.</p><p><strong>Methods: </strong>A search in MEDLINE and Embase identified studies published from 2016 to 2023. Studies were included if they were conducted in US SCD populations and reported complications/comorbidities and respective International Classification of Diseases, Clinical Modification (ICD-CM) codes. All identified complications/comorbidities and codes were reviewed by a certified medical coding expert and hematologist.</p><p><strong>Results: </strong>Of 1851 identified studies, 39 studies were included. The most reported complications/comorbidities were stroke, acute chest syndrome, pulmonary embolism, venous thromboembolism, and vaso-occlusive crisis. Most of the studies used ICD-9-CM codes (n = 21), while some studies used ICD-10-CM codes (n = 3) or both (n = 15), depending on the study period. Most codes reported in literature were heterogeneous across complications/comorbidities. The medical coding expert and hematologist recommended modifications for several conditions.</p><p><strong>Conclusion: </strong>While many studies we identified did not report their codes and were excluded from this review, the studies with codes exhibited diverse coding definitions. By providing a standardized set of diagnosis codes that were reported by studies and reviewed by a coding expert and hematologist, our review can serve as a foundation for accurately identifying complications/comorbidities in future research, and may reduce heterogeneity, enhance transparency, and improve reproducibility. Future efforts focused on validating these code lists are needed.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"33 9","pages":"e5769"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110531","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":"Contemporary Practice and Considerations for Real-World Data Source Identification and Feasibility Assessment.","authors":"Dony Patel, Sonia Guleria, Lina Titievsky, Susanna Flaherty, Nicholas Everage, Marta Korjagina, Sheuli Porkess, Tzuyung Douglas Kou, Deborah Layton","doi":"10.1002/pds.5862","DOIUrl":"10.1002/pds.5862","url":null,"abstract":"<p><strong>Purpose: </strong>There has been rapid growth in the variety and number of real-world data (RWD) sources, as well as the number of regulatory documents that provide guidance for assessing the suitability of RWD sources for pharmacoepidemiology studies. This study aims to assess differences in RWD guidance and variability in current practice for identifying and assessing RWD for studies with regulatory purpose.</p><p><strong>Methods: </strong>Key criteria for feasibility assessment were mapped against relevant regulatory guidance documents across US, EU, and Asia-Pacific regions. An online survey was designed and deployed to International Society for Pharmacoepidemiology members to understand current practice. Findings were summarized and used to inform key considerations and recommendations.</p><p><strong>Results: </strong>Eleven RWD guidance documents were identified and mapped against 14 RWD assessment criteria. Variability was seen across these documents in guidance for these criteria. Between December 2022 and January 2023, 37 survey respondents reported having used RWD for post-marketing commitments (34, 92%) and/or background epidemiology (28, 76%). RWD were mostly identified through literature (33, 89%) and data landscaping (26, 70%); guidance documents referenced included: Food and Drug Administration (20, 54%), European Network for Centres for Pharmacoepidemiology and Pharmacovigilance (17, 46%), European Medical Agency (16, 43%), and Structured Process to Identify Fit-For-Purpose Data (11, 30%). Challenges for conducting feasibility assessments included RWD accessibility, ability to complete validation, and RWD provider responsiveness.</p><p><strong>Conclusions: </strong>Existing guidelines are used extensively by researchers, but key criteria for RWD identification and feasibility assessment are not reflected consistently and challenges remain. Recommendations have been made reflecting study findings.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"33 9","pages":"e5862"},"PeriodicalIF":2.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110627","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}