Pharmacoepidemiology and Drug Safety最新文献

{"title":"Quantitative Benefit-Risk Assessment of Vaccination Against COVID-19: A Systematic Review.","authors":"E Claire Newbern, Lea Wildisen, Rita Verstraeten, Corinne Willame, Kevin Haynes, Bennett Levitan, Nicolas Praet","doi":"10.1002/pds.70099","DOIUrl":"10.1002/pds.70099","url":null,"abstract":"<p><strong>Purpose: </strong>With the introduction of COVID-19 vaccines, there has been a proliferation of quantitative benefit-risk assessments (qBRAs). Prior work on other types of vaccines has found that published qBRAs have not always clearly reported methods and/or results needed to assist in the application of the qBRA findings. The aim was to systematically identify, review, and critically assess published COVID-19 vaccine qBRA. The ultimate goal is to support the future development of robust qBRA for existing, new, and updated vaccines.</p><p><strong>Methods: </strong>We systematically reviewed COVID-19 vaccine qBRAs identified from multiple sources through April 17, 2023, including literature databases, selected Health Authority websites, and a grey literature search. We critically assessed whether key features typical of qBRA were presented in these reports.</p><p><strong>Results: </strong>We identified 37 COVID-19 vaccine qBRAs from screening 2220 publications and 18 other sources. The qBRAs were conducted on two mRNA and two adenoviral vector COVID-19 vaccines. Only one qBRA represented low- and middle-income countries. Although many qBRAs used simple calculations (n = 25), more complex models were presented in 15 reports. Simple approaches were able to employ stratification by age and/or sex to highlight safety issues affecting specific demographic groups and scenarios to account for changes in viral transmission and vaccine effectiveness over time. Details regarding data sources and analytic methods were missing or limited in some reports.</p><p><strong>Conclusions: </strong>This comprehensive description and critical assessment of COVID-19 vaccine qBRAs together with available guidance can be used to support the development of robust and transparent future vaccine qBRAs.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70099"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067099","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":"Expanding the OMOP Common Data Model to Support Perinatal Research in Network Studies.","authors":"Alicia Abellan, Edward Burn, Nhung T H Trinh, Theresa Burkard, Alison Callahan, Sergio Fernández-Bertolín, Eimir Hurley, Clara Rodriguez, Elena Segundo, Daniel R Morales, Hedvig M E Nordeng, Talita Duarte-Salles","doi":"10.1002/pds.70106","DOIUrl":"10.1002/pds.70106","url":null,"abstract":"<p><strong>Objectives: </strong>The Observational Medical Outcomes Partnership common data model (OMOP-CDM) is a useful tool for large-scale network analysis but currently lacks a structured approach to pregnancy episodes. We aimed to develop and implement a perinatal expansion for the OMOP-CDM to facilitate perinatal network research.</p><p><strong>Methods: </strong>We collaboratively developed a perinatal expansion with input from domain experts and stakeholders to reach consensus. The structure and vocabularies followed the OMOP-CDM ontological framework principles. We tested the expansion using SIDIAP and Norwegian databases. We developed a diagnostics package for quality control assessment and conducted a descriptive analysis on the captured perinatal data mapped to the OMOP-CDM.</p><p><strong>Results: </strong>The perinatal expansion consists of a pregnancy table and an infant table, each with required and optional variables incorporated into standardized vocabularies. Quality assessment of the perinatal expansion table in SIDIAP and Norwegian databases demonstrated accurate capture of perinatal characteristics. Descriptive analysis measured the number of pregnancies (SIDIAP: 646 530; Norway: 746 671), pregnancy outcomes (e.g., 0.5% stillbirths in SIDIAP and 0.4% in Norway), gestational length (median [IQR] in days, SIDIAP: 273 [56-280]; Norway: 280 [273-286]), number of infants (Norway: 758 806), and birth weight (median [IQR] in grams, Norway: 3520 [3175-3860)], among other relevant variables.</p><p><strong>Discussion and conclusion: </strong>We developed and implemented a perinatal expansion that captures important variables for perinatal research and allows interoperability with existing tables in the OMOP-CDM, which is expected to facilitate future network studies. The publicly available diagnostics package enables testing the implementation of the extension table and the quality and completeness of available data on pregnancy and pregnancy-related outcomes in databases mapped to the OMOP CDM.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70106"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414782","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":"Impact of Lookback Duration on the Performance of a Claims-Based Frailty Proxy in Women With Stage I-III Breast Cancer.","authors":"Emilie D Duchesneau, Til Stürmer, Katherine Reeder-Hayes, Dae Hyun Kim, Jessie K Edwards, Keturah R Faurot, Jennifer L Lund","doi":"10.1002/pds.70103","DOIUrl":"10.1002/pds.70103","url":null,"abstract":"<p><strong>Background: </strong>Frailty is an important prognostic indicator in older women with breast cancer. The Faurot frailty index, a validated claims-based frailty proxy measure, uses healthcare billing codes during a user-specified ascertainment window to predict frailty. We assessed how the duration of frailty ascertainment affected the ability of the Faurot frailty index to predict one-year mortality in women with stage I-II breast cancer.</p><p><strong>Methods: </strong>We included 128 857 women (66+ years) with stage I-III breast cancer in the SEER-Medicare database (2003-2019). The Faurot frailty index was calculated using 3-, 6-, 8-, and 12-month ascertainment windows prior to diagnosis or using all-available lookback. Associations between the Faurot frailty index using each window and one-year all-cause mortality were estimated using Kaplan-Meier curves. Discrimination of one-year mortality risk was assessed using C-statistics.</p><p><strong>Results: </strong>Five percent of women died during the year following diagnosis. Higher Faurot scores were associated with increased mortality risk for all frailty ascertainment windows. Differences in one-year mortality risk for women with high vs. low Faurot frailty scores were reduced when using all-available lookback (16% vs. 2%, difference = 15%, 95% CI 0.14-0.15) compared to shorter windows (e.g., 8 months: 25% vs. 2%, difference = 23%, 95% CI 0.22-0.24). C-statistics ranged from 0.758 (all-available lookback) to 0.770 (12 months) and were robust in subgroups defined by age, race, ethnicity, region, stage, and cancer subtype.</p><p><strong>Conclusions: </strong>The Faurot frailty index performed well across 3- to 12-month frailty ascertainment windows in women with breast cancer. Researchers should employ this index to address confounding by frailty in studies of cancer populations.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70103"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009445","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":"Successful Linkage of Electronic Medical Records and National Health Data System in Type 2 Diabetes Research: Methodological Insights and Implications.","authors":"Romane Le Goff, Sandrine Brice, Andrea Contini, Marjorie Boussac, Arnaud Souche, Fabien Belloc, Nicolas Coulombel, Cédric Collin, Amandine Gouverneur, Mathieu Molimard","doi":"10.1002/pds.70095","DOIUrl":"10.1002/pds.70095","url":null,"abstract":"<p><strong>Purpose: </strong>This study assesses success and methodological implications of linking IQVIA's Electronic Medical Records (EMR) of type 2 diabetes (T2D) patients with the National Health Data System (SNDS) database, a cornerstone process in healthcare research.</p><p><strong>Methods: </strong>The OREOT cohort was constituted by T2D patients identified in the IQVIA EMR from 2014 to 2018 and linked indirectly to SNDS database. The EMR database contains clinical records from general practitioner consultations, representing ~2.8% of the French population and the SNDS claims database covers over 99% of the French population's healthcare activities. Linkage success was evaluated by the linkage rate. Baseline patients' characteristics were described for both linked and non-linked patients.</p><p><strong>Results: </strong>Of the 291 408 T2D patients identified in the EMR, 244 656 (84%) were successfully linked. After technical data cleaning, 239 141 (82%) were finally linked. Linked and non-linked patients (n = 52,267) were aged 65 years and more frequently male (57% and 59%); half were obese, and most of comorbidities were consistent. Linked patients had more EMR consultations (median 32 vs 16), and more cardiovascular events (12% vs 7%) or chronic kidney disease (10% vs 7%).</p><p><strong>Conclusions: </strong>The successful linkage of EMR and SNDS databases provides valuable insights for future research in T2D and other chronic diseases requiring clinical data. This study demonstrates the feasibility of such data alignments, particularly in patients with complex health profiles or extensive medical records, and linkage potential to enhance real-world research quality. Despite higher prevalence of baseline comorbidities among linked patients, patients' characteristics were consistent with French T2D population.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70095"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024292","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":"Evaluating the Role of High-Dimensional Proxy Data in Confounding Adjustment in Multiple Sclerosis Research: A Case Study.","authors":"Mohammad Ehsanul Karim, Md Belal Hossain, Huah Shin Ng, Feng Zhu, Hanna A Frank, Helen Tremlett","doi":"10.1002/pds.70112","DOIUrl":"10.1002/pds.70112","url":null,"abstract":"<p><strong>Purpose: </strong>Given the historical use of limited confounders in multiple sclerosis (MS) studies utilizing administrative health data, this brief report evaluates the impact of incorporating high-dimensional proxy information on confounder adjustment in MS research. We have implemented high-dimensional propensity score (hdPS) and high-dimensional disease risk score (hdDRS) methods to assess changes in effect estimates for the association between disease-modifying drugs (DMDs) and all-cause mortality in an MS cohort from British Columbia (BC), Canada.</p><p><strong>Methods: </strong>We conducted a population-based retrospective study using linked administrative databases from BC, including health insurance registries, demographics, physician visits, hospitalizations, prescriptions, and vital statistics. The cohort comprised 19 360 individuals with MS, followed from January 1, 1996, to December 31, 2017. DMD exposure was defined as at least 180 days of use for beta-interferon or glatiramer acetate, or at least 90 days for other DMDs. The outcome was time to all-cause mortality. We compared Cox proportional hazards models adjusting for investigator-specified covariates with those incorporating additional empirical covariates using hdPS and hdDRS methods.</p><p><strong>Results: </strong>In the unadjusted analysis, DMD exposure was associated with a 69% lower risk of mortality (HR 0.31; 95% CI: 0.27-0.36). Adjusting for investigator-specified covariates, the adjusted hazard ratio (aHR) was 0.76 (95% CI: 0.65-0.89). HdPS analyses showed a 20%-23% lower mortality risk (aHRs: 0.77 to 0.80), while hdDRS analyses indicated a 19%-21% reduction (aHRs: 0.79 to 0.81).</p><p><strong>Conclusions: </strong>Incorporating high-dimensional proxy information resulted in minor variations in effect estimates compared to traditional covariate adjustment. These findings suggest that the impact of residual confounding in the question under consideration may be modest. Further research should explore additional data dimensions and replicate these findings across different datasets.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70112"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123363","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":"Hepatobiliary Adverse Events Associated With the KRAS p.G12C Inhibitor Sotorasib.","authors":"Connor Frey","doi":"10.1002/pds.70104","DOIUrl":"10.1002/pds.70104","url":null,"abstract":"<p><strong>Purpose: </strong>The p.G12C mutation in KRAS is commonly found in many cancers and was previously untreatable until drugs like sotorasib were developed. However, up to 15% of patients treated with sotorasib have experienced hepatobiliary adverse events. To investigate whether these side effects are more common among sotorasib users, a pharmacovigilance study is necessary.</p><p><strong>Methods: </strong>This study used the FDA adverse event reporting system (FAERS) database, a publicly available repository of reported drug adverse events, and AERSMine, an open-access pharmacovigilance tool, to investigate these adverse events.</p><p><strong>Results: </strong>A total of 428 hepatobiliary adverse events were linked to sotorasib. Hepatic cytolysis had the highest reported relative risk at 26.541 and a safety signal of 4.726. Elevated liver and biliary enzymes such as AST, ALT, ALP, and GGT were commonly observed, but with lower reported relative risk and safety signal values, which supports previous real-world reports.</p><p><strong>Conclusions: </strong>These findings highlight the hepatobiliary risks associated with sotorasib and underscore the importance of closely monitoring liver function in patients who are using the medication. This is particularly crucial for patients with hepatobiliary cancers, as disease progression and adverse events could be misinterpreted.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70104"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060144","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":"Use of Potentially Nephrotoxic Drugs in Type 2 Diabetes Patients on SGLT2i: A Trajectories Analysis.","authors":"Lanting Yang, Jingchuan Guo, Sandra L Kane-Gill, Nico Gabriel, Kerry M Empey, Kangho Suh, Levent Kirisci, Inmaculada Hernandez","doi":"10.1002/pds.70098","DOIUrl":"10.1002/pds.70098","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize trajectories of nephrotoxic potential (NxP) drug use among older adults with Type 2 Diabetes (T2D) treated with SGLT2is and identify associated patient characteristics.</p><p><strong>Methods: </strong>Using 2012-2019 Medicare data, we selected patients with T2D who filled at least one prescription for SGLT2is. Index date was the date of the first SGLT2i prescription filled. We quantified the number of drugs with NxP used every month during the first 12 months following the index date. The monthly counts of drugs with NxP were incorporated into the group-based trajectory model to identify groups with similar drug use patterns. Finally, we performed a multinomial logistic regression model to examine the association between patient characteristics and group membership.</p><p><strong>Results: </strong>The study cohort comprised 8811 Medicare beneficiaries with T2D who initiated SGLT2i during the study period with the mean age 67.5 ± 10.6 years. We identified 3 trajectories NxP drug use: no (n = 2142, 24%), low (n = 4752, 54%) and high (n = 1917, 22%) use of drugs with NxP, with patients falling into these categories based on the number of drugs with NxP they used over the time: no drugs, one drug, or two or more drugs. Age, gender, low-income subsidy eligibility and clinical characteristics were associated with group membership.</p><p><strong>Conclusions: </strong>We successfully identified three trajectory groups, with a substantial proportion of patients showing low use of drugs with NxP. Both social and clinical factors were associated with the use of NxP drugs.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70098"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024299","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":"Evaluating the Accuracy of Responses by Large Language Models for Information on Disease Epidemiology.","authors":"Kexin Zhu, Jiajie Zhang, Anton Klishin, Mario Esser, William A Blumentals, Juhaeri Juhaeri, Corinne Jouquelet-Royer, Sarah-Jo Sinnott","doi":"10.1002/pds.70111","DOIUrl":"10.1002/pds.70111","url":null,"abstract":"<p><strong>Purpose: </strong>Accurate background epidemiology of diseases are required in pharmacoepidemiologic research. We evaluated the performance of large language models (LLMs), including ChatGPT-3.5, ChatGPT-4, and Google Bard, when prompted with questions on disease frequency.</p><p><strong>Methods: </strong>A total of 21 questions on the prevalence and incidence of common and rare diseases were developed and submitted to each LLM twice on different dates. Benchmark data were obtained from literature searches targeting \"gold-standard\" references (e.g., government statistics, peer-reviewed articles). Accuracy was evaluated by comparing LLMs' responses to the benchmark data. Consistency was determined by comparing the responses to the same query submitted on different dates. The relevance and authenticity of references were evaluated.</p><p><strong>Results: </strong>Three LLMs generated 126 responses. In ChatGPT-4, 76.2% of responses were accurate, which was higher compared to 50.0% in Bard and 45.2% in ChatGPT-3.5. ChatGPT-4 exhibited higher consistency (71.4%) than Bard (57.9%) or ChatGPT-3.5 (46.7%). ChatGPT-4 provided 52 references with 27 (51.9%) providing relevant information, and all were authentic. Only 9.2% (10/109) of references from Bard were relevant. Of 65/109 unique references, 67.7% were authentic, 7.7% provided insufficient information for access, 10.8% provided inaccurate citation, and 13.8% were non-existent/fabricated. ChatGPT-3.5 did not provide any references.</p><p><strong>Conclusions: </strong>ChatGPT-4 outperformed in retrieving information on disease epidemiology compared to Bard and ChatGPT-3.5. However, all three LLMs presented inaccurate responses, including irrelevant, incomplete, or fabricated references. Such limitations preclude the utility of the current forms of LLMs in obtaining accurate disease epidemiology by researchers in the pharmaceutical industry, in academia, or in the regulatory setting.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70111"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123362","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":"Validation of Immune-Related Adverse Event (irAE) Case Definitions in a Real-World Lung Cancer Population.","authors":"James S Heyward, Jodi B Segal, Hemalkumar B Mehta, Joseph C Murray","doi":"10.1002/pds.70100","DOIUrl":"10.1002/pds.70100","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The use of real-world data is increasing to examine immune-related adverse event (irAE) incidence and risk factors in immune checkpoint inhibitor (ICI) users. We aimed to validate five case definition algorithms for irAE in a Johns Hopkins lung cancer registry.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective cohort study using linked electronic health record (EHR) and cancer registry data from a large academic healthcare system. The Lung Immunotherapy irAE Monitoring Registry assesses irAEs in a group of patients treated for lung cancer at Johns Hopkins Medicine from 2013 to 2020. We used data from inpatient, outpatient, and emergency department encounters, including International Classification of Disease (ICD)-10 codes and medication administration records to classify the presence or absence of irAEs using five distinct algorithms. These algorithms included three that used both diagnosis (Dx) and medication (Rx) codes, one that used Rx codes only, and one that used Dx codes only, ranging from most numerous criteria (most stringent) to least numerous criteria (least stringent). We compared all five algorithms' performances against chart review-ascertained irAE status and reported sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and C-statistic (C-stat), with 95% confidence intervals (CI). We also explored algorithm performance by specific organ system toxicities and by Common Terminology Criteria for Adverse Events (CTCAE) severity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study cohort included 354 patients with ICI exposure for whom chart review-ascertained irAE status was available. A total of 89 (25.1%) experienced at least one irAE (38 pneumonitis, 12 arthritis, 12 colitis, 7 thyroiditis, and others). Across algorithm versions, Se ranged from 59.3% to 93.2% in descending order of algorithm stringency; Sp ranged from 21.0% to 77.6% in ascending order of algorithm stringency, and PPV ranged from 19.1% to 34.7%. The C-stat ranged from 0.57 (95% CI, 0.53-0.61) (Dx codes only) to 0.71 (0.64-0.77) (Rx codes only). For severe irAE (CTCAE Grade 3-5), all algorithms performed better than in the primary analysis, and four exceeded the threshold for usefulness as a measurement tool (maximum C-stat: 0.78 [0.71-0.85] [Rx codes only]). For severe tissue-specific toxicities, algorithmic detection of irAE pneumonitis, colitis, and hepatitis performed better than for the overall group of severe toxicities. Generally, the algorithm versions depicted a Se-Sp tradeoff depending on algorithm stringency.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In this validation study of five irAE case definition algorithms, a combination of ICD-10 codes and medication administration codes generally perform well to identify more severe irAE (CTCAE Grade 3-5), and severe pneumonitis, hepatitis, and colitis (common irAEs) among all possible irAE severity levels and sites. Medication codes alone ","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70100"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441239","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":"Impact of Regulatory Action on Dose Maximalization for Vitamin B6 Dietary Supplements on the Reporting Pattern for Neuropathy.","authors":"Florence van Hunsel, Joep Scholl, Misha Vrolijk, Corine Ekhart","doi":"10.1002/pds.70108","DOIUrl":"10.1002/pds.70108","url":null,"abstract":"<p><strong>Background: </strong>Vitamin B6 deficiency is linked to neurological disorders. However, supplementation with high doses of vitamin B6 has also been linked to neuropathy as an adverse drug reaction. Review of cases from the Dutch Spontaneous Reporting System (SRS) and other data led to a regulatory action to lower the maximum daily dose (DD) of vitamin B6 in supplements to 21 mg/day from October 1, 2018.</p><p><strong>Purpose: </strong>The aim of this study was to investigate if there was an effect of the regulatory action in 2018 on maximum daily dosage for vitamin B6 on the reporting pattern of neuropathy to the SRS in the Netherlands.</p><p><strong>Methods: </strong>We investigated trends in the number of reports received until December 31, 2023, DD mentioned in the reports, and the correlation between DD and plasma vitamin B6 levels. A change point analysis was used to get insight into the pattern of reports over time.</p><p><strong>Results: </strong>Two hundred and twenty-four reports were included. After the regulatory action for dose maximization from October 2018, only one report mentions a dosage which is much higher than the recommended 21 mg DD. Only 15% of the variability in plasma levels mentioned in reports can be explained by the DD. Twelve statistical change points were noted, especially around some peaks in the reporting pattern for instance in 2018. However, from the second half of 2019, the number of reports on vitamin B6 and neuropathy per time period is lower and no change points were detected.</p><p><strong>Conclusions: </strong>Although our study has limitations, we clearly see an effect of regulatory action on the doses of vitamin B6 used in neuropathy reports. However, some cases describing neuropathy related to vitamin B6 supplementation with lower doses are still reported after the regulatory action in 2018. Therefore, the association between low-dose vitamin B6 products and neuropathy should be studied further.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"34 2","pages":"e70108"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067097","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}