Pharmacoepidemiology and Drug Safety最新文献

{"title":"Trajectories Associated With the Use and Deprescription of Benzodiazepines and Z-Drugs in a Network of Geriatric Outpatient Clinics.","authors":"Nelson Machado do Carmo Júnior, Mariana Martins Gonzaga do Nascimento, Antônio Ignácio de Loyola Filho, Daniela Castelo Azevedo, Estevão Alves Valle, Edna Afonso Reis","doi":"10.1002/pds.70419","DOIUrl":"10.1002/pds.70419","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the trajectories of benzodiazepine (BZD) and Z-drug use among older adults (n = 3590) followed in a network of geriatric outpatient clinics in Brazil.</p><p><strong>Methods: </strong>This longitudinal study evaluated BZD and Z-drug use over a 24-month follow-up period. The proportion of use at baseline and at the end of the study period was compared using the McNemar test. Two trajectories were considered: started using and stopped using. Comparisons between trajectories and independent variables were performed using Pearson's chi-square test. Variables with p < 0.20 were eligible for multivariate analysis. Multivariate models were also used to identify factors associated with BZD or Z-drug use at baseline and with trajectories of initiation and discontinuation. Odds ratios (OR) with 95% confidence intervals were estimated.</p><p><strong>Results: </strong>A small but significant reduction in overall BZD or Z-drug use was observed (17.4% to 16.0%; p = 0.007), with a marked decrease in isolated Z-drug use (6.1% to 4.0%; p < 0.001). At baseline, use was associated with female sex (OR = 1.48; 95% CI 1.19-1.84), age 60-74 years (OR = 1.64; 95% CI 1.29-2.10), having ≥ 2 fall-related conditions (OR = 2.53; 95% CI 1.94-3.31), higher frailty scores, and cognitive dysfunction (OR = 1.32; 95% CI 1.00-1.74). Initiation was associated with pharmacist consultations during follow-up (OR = 5.01; 95% CI 2.88-8.71), depression (OR = 2.59; 95% CI 1.80-3.73), insomnia (OR = 1.97; 95% CI 1.19-3.25), and panic syndrome. Pharmacist consultation was also associated with discontinuation (OR = 0.34; 95% CI 0.15-0.76).</p><p><strong>Conclusions: </strong>Clinical vulnerability and psychiatric conditions were associated with BZD or Z-drug use and initiation, while pharmacist consultations were associated with both initiation and discontinuation trajectories.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70419"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284125","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":"Provider Perspectives to Inform a Patient-Facing Decision Aid on Oral Corticosteroid Use During Pregnancy and Evaluation of the Aid.","authors":"Kristin Palmsten, Elisabeth A Seburg, Jeanette Y Ziegenfuss, Gabriela Vazquez-Benitez, Meghan M JaKa, Christina D Chambers, Lyndsay A Avalos, Elyse O Kharbanda","doi":"10.1002/pds.70413","DOIUrl":"10.1002/pds.70413","url":null,"abstract":"<p><strong>Purpose: </strong>We previously identified patient need for a decision aid on oral corticosteroid (OCS) use during pregnancy that could be used to support discussions between providers and patients. In the current study, we aimed to identify healthcare provider needs for a decision aid on OCS use during pregnancy and then evaluated the usefulness of the decision aid that we developed.</p><p><strong>Methods: </strong>Before developing a decision aid on OCS use during pregnancy, we conducted semi-structured interviews with providers from one health system to understand needs for an aid for counseling patients about OCS use during pregnancy. To assess the usefulness of the decision aid that we developed, providers reviewed the decision aid and responded to survey questions. Also, the survey assessed provider knowledge regarding counseling on OCS use during pregnancy before and after reviewing the aid (knowledge scores range 0-15).</p><p><strong>Results: </strong>In interviews, all providers (n = 13) reported that a patient-facing decision aid would be useful when discussing OCS use during pregnancy because it would give information to patients and providers, and it would facilitate decision making. Among the providers who participated in the survey (n = 68), two-thirds reported after reviewing the aid that they would usually or always use the decision aid in conversations about OCS treatment during pregnancy. All survey participants reported that they would recommend the decision aid to colleagues. Overall, providers' median knowledge score improved by 1 (IQ range 3) after reviewing the decision aid (p < 0.01).</p><p><strong>Conclusions: </strong>We established the usefulness of a decision aid on OCS use during pregnancy for providers.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70413"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271831","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":"DrugUtilisation: An R Package to Support Drug Utilisation Research Using the OMOP Common Data Model.","authors":"Yuchen Guo, Edward Burn, Annika M Jödicke, Núria Mercadé-Besora, Kim Lopez-Güell, Xihang Chen, Mike Du, Xintong Li, Raivo Kolde, Marek Oja, Mees Mosseveld, Katia Verhamme, Julieta Politi, Antonella Delmestri, Wai Yi Man, Peter Rijnbeek, Daniel Prieto-Alhambra, Martí Català","doi":"10.1002/pds.70433","DOIUrl":"10.1002/pds.70433","url":null,"abstract":"<p><strong>Purpose: </strong>To develop and describe DrugUtilisation, an open-source R package that facilitates drug utilisation studies using data mapped to the OMOP Common Data Model (CDM).</p><p><strong>Methods: </strong>Core functionalities include creating drug user cohorts, identifying and summarising indications, describing the duration and dose of medication/s and assessing treatment adherence. The package works with packages developed within the DARWIN EU initiative to support study-specific workflows. We show the package's workflow by analysing the use of simvastatin in three European real-world databases.</p><p><strong>Results: </strong>This paper outlines the DrugUtilisation package's functions and demonstrates their application with a clinical example of simvastatin use in databases from the United Kingdom, Estonia and the Netherlands. We generated results including cohort counts, indication summaries, measures of dose and duration, as well as publication-ready tables and figures. We implemented comprehensive unit tests and standardised output format, which ensured consistency across databases and minimised coding errors.</p><p><strong>Conclusion: </strong>The development of this software allows for researchers to quickly perform common drug utilisation analyses, while also providing the foundation for additional, bespoke study-specific analyses.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70433"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448616","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":"Effectiveness of Metformin in Preventing Colorectal Cancer Among Japanese Patients With Type 2 Diabetes: A Target Trial Emulation.","authors":"Shunsuke Hiroki, Toshiki Fukasawa, Munenori Honda, Koji Kawakami","doi":"10.1002/pds.70429","DOIUrl":"10.1002/pds.70429","url":null,"abstract":"<p><strong>Purpose: </strong>Observational studies have repeatedly reported lower cancer incidence among metformin users than nonusers, but findings are inconsistent and often affected by issues such as immortal time, unclear comparators, and use of total cancer as a composite outcome, which precludes adequate adjustment for site-specific confounding. These limitations can be mitigated by explicitly emulating a target trial with a suitable active comparator.</p><p><strong>Methods: </strong>We emulated a target trial using a Japanese claims database (April 2014-March 2024) to assess whether metformin reduces colorectal cancer (CRC) risk compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes. DPP-4is served as an active comparator because they are widely used as first-line alternatives in Japan and have no clear evidence of affecting CRC risk. We estimated the observational analogue of the per-protocol effect using pooled logistic regression with inverse probability weighting to adjust for baseline and time-varying confounders.</p><p><strong>Results: </strong>Among 26 273 metformin users and 108 299 DPP-4i users, the 5-year risk of CRC was 1.55% (95% confidence interval, 1.16 to 2.04) versus 1.26% (1.13 to 1.41), yielding a risk difference of 0.29% (-0.12 to 0.79) and a risk ratio of 1.23 (0.91 to 1.66).</p><p><strong>Conclusions: </strong>Metformin use did not reduce the 5-year risk of CRC compared with DPP-4is. This finding is consistent with meta-analyses of randomized trials and contrasts with earlier observational reports of substantial benefit, which were likely inflated by methodological flaws. Explicitly emulating a target trial minimized design-related biases and provided estimates that support causal interpretation.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70429"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382632","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":"Trends in Pharmacist-Prescribed Dispensing Records of HIV Pre-Exposure (2020-2025) and Post-Exposure Prophylaxis (2020-2024) in Brazil: A Time Series Analysis.","authors":"Gustavo Magno Baldin Tiguman, Dyego Carlos Souza Anacleto de Araújo, Patricia Melo Aguiar","doi":"10.1002/pds.70422","DOIUrl":"10.1002/pds.70422","url":null,"abstract":"<p><strong>Purpose: </strong>Pharmacist prescribing of HIV pre-exposure (PrEP) and post-exposure prophylaxis (PEP) is an emerging strategy to expand access to HIV prevention, but real-world evidence on its implementation remains limited. We assessed national and regional trends in pharmacist-prescribed dispensing records of PrEP (2020-2025) and PEP (2020-2024) in Brazil.</p><p><strong>Methods: </strong>Nationwide time series analysis using databases from the Ministry of Health. The primary outcome was pharmacist-prescribed PrEP and PEP dispensing records per 100 000 adults per year. Joinpoint regression was used to estimate average annual percent change (AAPC) and 95% confidence intervals (95% CIs).</p><p><strong>Results: </strong>Pharmacists prescribed 27 126 (2.80%) of 969 536 PrEP records and 13 073 (1.97%) of 664 000 PEP records. The frequency of pharmacist-prescribed records in relation to all prescribers increased (PrEP: 0.22% to 5.77%; PEP: 0.12% to 4.59%). National pharmacist-prescribed PrEP dispensing increased from 0.10 to 6.24 per 100 000 adults (AAPC: 120.80; 95% CI 71.96 to 189.84; p < 0.001), while pharmacist-prescribed PEP dispensing increased from 0.07 to 4.93 per 100 000 adults (AAPC: 166.62; 95% CI 68.66 to 313.26; p < 0.001). The Southeast had the highest absolute rates for both strategies. Significant upward trends were observed in all five regions for PrEP, and in the Southeast, Northeast, and Center-West for PEP. The national PrEP rate stabilized between 2024 and 2025.</p><p><strong>Conclusions: </strong>Pharmacist prescribing of HIV prophylactic medications significantly increased in Brazil since 2020 and may potentially represent an important mechanism to broaden access to HIV prevention. However, regional differences may underscore the need for targeted policy interventions to address geographic implementation gaps.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70422"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376517","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":"Association Between EGFR-TKI-Associated Skin Rash and Recorded Mortality in Non-Small Cell Lung Cancer: A Real-World Analysis Accounting for Immortal Time Bias.","authors":"Yasutaka Ihara, Yukihiro Nakamura, Shoichiro Yamamoto","doi":"10.1002/pds.70428","DOIUrl":"https://doi.org/10.1002/pds.70428","url":null,"abstract":"<p><strong>Purpose: </strong>Skin rash during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy has been associated with better outcomes in non-small cell lung cancer (NSCLC), but previous studies may have overestimated this association because of immortal time bias. We evaluated the association between EGFR-TKI-associated skin rash and mortality while accounting for rash timing.</p><p><strong>Methods: </strong>We identified patients with NSCLC who initiated first-line EGFR-TKIs between August 2018 and December 2024 using a Japanese claims database. EGFR-TKI-associated skin rash was defined using a qualifying diagnosis and rash-related treatment recorded in the same calendar month. We performed time-dependent propensity score sequential matching: each patient who newly developed skin rash was matched on the rash-onset day to patients still at risk who had not yet developed skin rash; follow-up started on the matched day. For comparison, we also performed an analysis that did not account for immortal time bias and landmark analyses.</p><p><strong>Results: </strong>Among 11 830 eligible patients, 560 developed incident skin rash. In the time-dependent propensity score sequential matching analysis, 560 patients with skin rash were matched to 5600 patients without skin rash, and skin rash was associated with lower recorded mortality (HR, 0.621; 95% CI, 0.404-0.953). The estimate was stronger in the analysis not accounting for immortal time bias (HR, 0.410), whereas the association was attenuated in landmark analyses.</p><p><strong>Conclusions: </strong>EGFR-TKI-associated skin rash was associated with lower recorded mortality, but the association was weaker after accounting for immortal time bias. Prior studies may have overestimated this association.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70428"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361535","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 Drug-Environment Interaction Between PM₂ _.5 Concentration and Corticosteroid Use on Cardiovascular and Thromboembolic Events in Older Adults.","authors":"Shu-Ping Huang, Chien-Chou Su, Rachel Nethery, Kevin Josey, Benjamin Bates, David Robinson, Poonam Gandhi, Melanie Rua, Ashwaghosha Parthasarathi, Soko Setoguchi, Yea-Huei Kao Yang","doi":"10.1002/pds.70414","DOIUrl":"10.1002/pds.70414","url":null,"abstract":"<p><strong>Background: </strong>Few studies have investigated the interaction between drug-environment despite the plausibility and concern. We sought to explore the synergistic effects of corticosteroids and PM_2.5 on cardiovascular and thromboembolic events in high-risk older adults in Taiwan.</p><p><strong>Objectives: </strong>To assess the synergistic effect of corticosteroid use and PM_2.5 exposure on cardiovascular and thromboembolic events and all cause mortality among elderly individuals in Taiwan.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the Taiwan National Health Insurance database from 2009 to 2019. We included patients aged 65 years or older and at high risk for cardiovascular and thromboembolic events. Exposures included corticosteroid therapy and seasonal mean PM_2.5. Primary outcomes included myocardial infarction or acute coronary syndrome, ischemic stroke or transient ischemic attack, heart failure, venous thromboembolism, atrial fibrillation, and all-cause mortality. We then fitted history-adjusted marginal structural Cox proportional hazard models to investigate both the independent and synergistic effects of PM_2.5 and corticosteroid use on the CTE outcomes. We measured whether there was a sufficient cause interaction between PM_2.5 and corticosteroids using estimates of relative excess risk due to interaction (RERI).</p><p><strong>Results: </strong>The cohort included 373 402 participants, with average age at index date 73.6 ± 7.2 years; 57.7% of cohort members were female. During the study period, 1 614 331 (43.2%) participants had at least one corticosteroid prescription. The average PM_2.5 concentration was 28.3 ± 17.4 μg/m³. Increasing PM_2.5 from 15 to 20 μg/m³ resulted in significantly increased excess risk due to interaction (RERI [95% CI]) for all-cause mortality (3.1% [0.27%, 5.9%]).</p><p><strong>Conclusions: </strong>A synergistic effect between seasonal PM_2.5 exposure and corticosteroid use was found on all-cause mortality in elderly patients at high risk for cardiovascular and thromboembolic events.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70414"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391384","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":"Uptake and Use of Biologic Therapies in Paediatric Immune-Mediated Inflammatory Diseases: An Australian Population-Based Study.","authors":"Jun Ni Ho, Jodie Hillen, Natasha Nassar, Helga Zoega, Timothy Beukelman, Nicole Pratt, Benjamin Daniels","doi":"10.1002/pds.70412","DOIUrl":"10.1002/pds.70412","url":null,"abstract":"<p><strong>Purpose: </strong>To quantify the real-world use and describe characteristics of paediatric patients initiating biologic medicines for immune-mediated inflammatory diseases (IMIDs).</p><p><strong>Methods: </strong>Dispensing claims for Australians aged less than 18 years were used to examine uptake and use trends of nine biologic medicines used for the treatment of IMIDs. A 15% random sample of the population was used for dispensings between 2013 and 2017, and a 30% sample for dispensings between 2017 and 2020. Incidence and prevalence rates of use per 1 000 000 population per year were calculated. Patient demographics at the time of first dispensing were determined and the number of unique medicines dispensed per person across the study period was calculated.</p><p><strong>Results: </strong>Incidence of use of biologics increased from 108 per million in 2014 to 192 per million in 2020, while prevalence increased from 352 per million to 877 per million over the same period. 1131 children were dispensed at least one biologic medicine; infliximab, adalimumab or etanercept accounted for 80% of dispensings. Mean age at first dispensing was 14 years (standard deviation: 3 years) and 51% were male. Of children initiated on biologics, 55% were first dispensed treatment for inflammatory bowel diseases and 29% for inflammatory arthropathies. While most children were dispensed only one unique biologic medicine, 15% were dispensed two, and 3% three or more over the study period.</p><p><strong>Conclusions: </strong>These results suggest that children remain on treatment for extended periods of time and nearly one in five children were dispensed multiple biologic medicines. Post-market studies should be prioritised to monitor safety among these groups.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70412"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13322984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369228","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":"Core Concepts in Pharmacoepidemiology-Round 3: Call for Writing Groups.","authors":"Kristian B Filion, Jennifer L Lund","doi":"10.1002/pds.70425","DOIUrl":"10.1002/pds.70425","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70425"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423071","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":"How Negative Controls Are Used in Pharmacoepidemiology: A Methodological Scoping Review of Real-World Observational Studies of Glucagon-Like Peptide-1 Receptor Agonists.","authors":"Zhengxuan Li, Yinan Huang, Hua Chen, Jieni Li","doi":"10.1002/pds.70420","DOIUrl":"10.1002/pds.70420","url":null,"abstract":"<p><p>Negative controls (NCs) are increasingly used in real-world observational studies to detect residual confounding and systematic bias, but their implementation and reporting remain heterogeneous in applied pharmacoepidemiology. We conducted a methodological scoping review to characterize how NCs were selected, implemented, reported, and interpreted in real-world studies evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for non-indicated clinical outcomes. We systematically searched PubMed and Embase from database inception through November 2025 and additionally screened reference lists of included studies. Eligible studies used real-world data, applied an observational analytic framework to evaluate GLP-1 RAs, focused on non-indicated outcomes, and explicitly incorporated NCs for bias detection, falsification, validation, or empirical calibration. Among 489 records identified, 42 studies met the inclusion criteria. Most studies were cohort-based and were conducted in diabetes-related populations using electronic health records or administrative claims. Negative control outcomes (NCOs) were the dominant approach, whereas negative control exposures (NCEs), positive controls, and empirical calibration were less common. An explicit rationale for NC selection was reported in most studies, but none of the included studies explicitly discussed the assumptions underlying NC analysis. Most NC findings were reported as null or consistent with expectations, and were primarily used to support validity or robustness rather than to materially alter interpretation. Overall, our findings suggest that the current use of NCs in GLP-1 RA observational research has increased, while standardized implementation and reporting have lagged. Greater transparency regarding why NCs were selected, what source of bias they were intended to probe, how results were interpreted, and whether they changed analytic conclusions may improve the credibility and interpretability of real-world evidence in this rapidly evolving therapeutic area.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70420"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423041","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}