Drug Safety最新文献

{"title":"Implementation Science for Effective Risk Management of Medicines: A Call for Global Action.","authors":"Meredith Y Smith, Priya Bahri, Delese Mimi Darko, Alex N O Dodoo, Adrien Inoubli, Elaine H Morrato, Christine Perera, Shanti Pal","doi":"10.1007/s40264-026-01702-5","DOIUrl":"10.1007/s40264-026-01702-5","url":null,"abstract":"<p><p>Pharmaceutical risk minimization, as an essential element of pharmacovigilance, aims to reduce medicinal product risks in order to improve a product's benefit-risk profile. However, to date the practical application of risk minimization has proved challenging. In particular, risk minimization standards developed by and for high-income countries have been shown to have limited suitability in low and middle income countries (LMICs) and high-income countries have struggled to deliver these programs with consistently high quality and demonstrable long-term impact. The World Health Organization's new 2025 framework for pharmacovigilance-'The Global Smart Pharmacovigilance Strategy'-calls for developing comprehensive and sustainable safety monitoring and risk management practices as integral components of healthcare and regulatory systems in all member countries globally. The field of implementation science offers a robust set of approaches to address current gaps and challenges in risk minimization, one that can help meet the needs of twenty-first century pharmacovigilance. We call for the convening of an internationally representative expert forum to develop a pragmatic framework and set of recommendations regarding the application of implementation science good practices to advance risk minimization for medicinal products globally. The framework and recommendations should be practical, sustainable and equally applicable for use in LMIC and high-income countries. In addition, the framework and recommendations should be accompanied by a blueprint for implementation science capacity building as well as a dissemination plan for promoting uptake of the framework and recommendations by industry and regulatory authorities worldwide.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and Opportunities for Signal Detection During Public Health Emergencies: An Historical Re-evaluation of the Disproportionality Analysis of the ADR Reporting of Anti-COVID-19 Monoclonal Antibodies in Vigibase.","authors":"Nicoletta Luxi, Chiara Bellitto, Francesco Ciccimarra, Fabio Scapini, Elena Arzenton, Francesco Maccarrone, Ugo Moretti, Emanuel Raschi, Elisabetta Poluzzi, Daniele Focosi, Jacopo Angelini, Pasquale De Nardo, Alessia Savoldi, Evelina Tacconelli, Gianluca Trifirò, Marco Tuccori","doi":"10.1007/s40264-026-01705-2","DOIUrl":"https://doi.org/10.1007/s40264-026-01705-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Anti-spike monoclonal antibodies (mAbs) for early treatment of COVID-19 represented a significant improvement in the pharmacological management of the SARS-COV-2 pandemic, especially in early phases, but the continuous emergence of novel virus variants of concern (VoC) required a rapid and continuous benefit-risk assessment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To identify possible unexplored safety signals of anti-SARS-CoV-2 mAbs through disproportionality analysis using VigiBase, the World Health Organization (WHO) global pharmacovigilance database.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a disproportionality analysis of VigiBase (February 2020-December 2023). All de-duplicated individual case safety reports (ICSRs) for bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, regdanvimab, sotrovimab, and tixagevimab/cilgavimab were retrieved. Descriptive analyses of ICSRs and distribution of suspected adverse drug reactions across VoC-defined periods (Alpha, Delta, Omicron) were performed. Disproportionality analysis was conducted and reported in accordance with the READUS-PV guideline. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated at the MedDRA Preferred Term (PT) level, using the entire database as reference (excluding vaccines). Statistically significant drug-adverse reaction pairs included in the EMA Important Medical Event (IME) list and not described in the Summary of Product Characteristics (SmPC) were identified as potential safety signals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 15,250 de-duplicated ICSRs, casirivimab/imdevimab accounted for the majority of reports (33.5%). Most cases involved female patients aged 45-64 years, predominantly reported from the Americas. Overall, 42,799 drug-adverse reaction pairs were identified, 33,948 (79.3%) of which were identified after filtering out, and 3047 (9.0%) were IMEs. Eighty-three unique drug-adverse reaction pairs had a statistically significant RORs, among which 56 (67.5%) were not listed in the SmPC. Bamlanivimab, as both monotherapy and in combination with etesevimab, showed increased reporting of several cardiac adverse events, including acute myocardial infarction (MI) and cardiac arrest. For tixagevimab/cilgavimab, disproportionality was found for acute MI (N = 6; ROR 12.7, 95% CI 5.7-28.4) and atrial fibrillation (N = 29; ROR 9.0, 95% CI 6.2-13.0). For regdanvimab, disproportionality emerged for hypokalemia (N = 13; ROR 5.8, 95% CI 3.4-10.1). For casirivimab/imdevimab, 5 out of 15 PTs were classified as adverse event of special interest: seizure-like phenomena (N = 8; ROR, 44.2; 95% CI 21.9-89.1), Guillain-Barré syndrome (N = 6; ROR 13.4, 95% CI 6.0-30.0), encephalopathy (N = 13; ROR 5.4, 95% CI 3.1-9.3), generalized tonic-clonic seizure (N = 9; ROR 5.0, 95% CI 2.6-9.7), and seizure (N = 57; ROR 3.1, 95% CI 2.4-4.0).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This analysis identified potential cardiovascular and neuro","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presence of Benzodiazepines in Aquatic Environments: A Systematic Review of the Literature.","authors":"Jacopo Grisotto, Irene Cristini, Salvatore Crisafulli, Francesco Ciccimarra, Francesca Patuzzi, Federica Soardo, Elisabetta Mariavittoria Giunco, Giovanna Paolone, Gianluca Trifirò","doi":"10.1007/s40264-026-01703-4","DOIUrl":"https://doi.org/10.1007/s40264-026-01703-4","url":null,"abstract":"<p><strong>Introduction: </strong>Pharmaceuticals in aquatic environments are a growing environmental concern. Because of their widespread use and poor removal by conventional wastewater treatment, benzodiazepines are frequently detected in treated effluents.</p><p><strong>Objective: </strong>To synthesise global evidence on the occurrence and distribution of benzodiazepines and their metabolites across the urban water cycle.</p><p><strong>Methods: </strong>The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in performing this systematic review. Bibliographic databases PubMed (including PubMed Central and Medline), Embase and Scopus were searched, from the inception date to July 26th, 2024, using query terms related to benzodiazepines (BDZs) and water pollution. Titles, abstracts and full text of the articles were independently evaluated by six review authors.</p><p><strong>Results: </strong>Of 1973 records identified, 119 studies published between 2001 and 2024 met the inclusion criteria. Most research (N = 102) was conducted in European countries, followed by Asia (N = 29), America (N = 16), Africa (N = 5) and Australia (N = 2). Reported BDZ concentrations varied widely across the included studies, ranging from below analytical detection limits to several thousand ng/L, depending on the specific compound, sampling strategy, analytical technique, and environmental matrix. Most of the included studies searched BDZs in surface water (N = 61), followed by wastewater treatment plants (WWTP) effluents (N = 47) and WWTP influents (N = 40). Diazepam (N = 64 studies), oxazepam (N = 58 studies), lorazepam (N = 45 studies), temazepam (N = 31 studies) and alprazolam (N = 29 studies) were the most frequently detected compounds.</p><p><strong>Conclusion: </strong>Global data highlight the need for standardised monitoring frameworks, targeted sources mitigation, and advanced water treatment technologies capable of efficiently removing chemically stable pharmaceutical compounds. Strengthening these approaches is essential to reduce ecological risks, minimise human exposure, and safeguard the long-term integrity of aquatic ecosystems.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmenting Medical Judgment in Signal Confirmation: Design Considerations for an AI-Enabled Causality Assessment Framework.","authors":"Tarek A Hammad, Justine Rochon, Salman Afsar, Sue H Lee, Dona M Ely, Neda Hassanpour, Andrew Bate","doi":"10.1007/s40264-026-01700-7","DOIUrl":"https://doi.org/10.1007/s40264-026-01700-7","url":null,"abstract":"<p><p>The safety signal assessment process evaluates the potential causal association between a medicinal product and a specific adverse event by integrating multiple streams of evidence. Existing causality assessment methods remain challenged by the considerable manual effort involved and by decision variability, even when drawing on the same underlying domains of evidence. This work addresses the need in contemporary pharmacovigilance for a more efficient and harmonized approach to signal confirmation that preserves scientific rigor while mitigating the limitations of the current assessment processes. To address this need, the article describes design considerations for an artificial intelligence (AI)-enabled, integrated approach for safety signal causality assessment, referred to as Signal Confirmation through Omnichannel Pharmacovigilance Evidence (PV-SCOPE). As a conceptual proof-of-principle, the proposed approach describes how the Hammad-Afsar holistic causality assessment framework could be operationalized through multimodal evidence integration and structured approach, while preserving the central role of clinical and scientific reasoning in causality assessment. Because the AI workflow is presented as a design-oriented framework rather than a completed or validated model, the article focuses on architectural logic, governance, and validation and regulatory requirements rather than reporting performance results.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guillain-Barré Syndrome Following Recombinant Zoster Vaccine in US Medicare Adults Age 65 Years or Older.","authors":"Susan Dos Reis, Yueh-Yi Chiang, Alejandro Amill-Rosario, Haeyoung Lee, Abree Johnson, Kathleen Ryan, Driss Oraichi, Harry Seifert, Huifeng Yun, Susan Gamble, O'Mareen Spence","doi":"10.1007/s40264-026-01658-6","DOIUrl":"10.1007/s40264-026-01658-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Pre- and post-marketing studies detected Guillain-Barré syndrome following recombinant zoster vaccine. This study evaluated new-onset Guillain-Barré syndrome following recombinant zoster vaccine in older US adults.</p><p><strong>Methods: </strong>Using the Medicare Chronic Condition Warehouse administrative data, we implemented a self-controlled risk interval case-only design with a 1- to 42-day risk window and a 43- to 84-day control window following recombinant zoster vaccine. Participants were Medicare beneficiaries aged ≥65 years who received at least one dose of the recombinant zoster vaccine two-dose regimen from 2018 to 2020. New-onset Guillain-Barré syndrome was identified using an algorithm requiring an International Classification of Disease, Tenth Revision diagnosis code of G61.0 in the primary position in an inpatient setting or in any other setting followed by an inpatient encounter within 7 days, with no Guillain-Barré syndrome in the preceding 365 days. Conditional Poisson regression models estimated the relative risk and 95% confidence intervals (CIs). We estimated the attributable risk and 95% CI. Sensitivity analyses examined dose-specific effects, 60- to 183-day dose spacing, and coronavirus disease 2019 and seasonality.</p><p><strong>Results: </strong>Of 3,383,799 eligible participants, 75 experienced new-onset Guillain-Barré syndrome. The primary analysis detected a relative risk of 3.15 (95% CI 1.82, 5.68) and an attributable risk of 6.59 per 1,000,000 doses (95% CI 4.35, 7.96). The dose-specific analysis detected a relative risk of 5.33 (95% CI 2.59, 12.36) for dose 1. The coronavirus disease 2019 and seasonality analyses revealed an increased risk. Dose 2 and the 60- to 183-day dose spacing were not significant.</p><p><strong>Conclusions: </strong>The elevated risk of new-onset Guillain-Barré syndrome among US Medicare beneficiaries aged ≥65 years was detected after recombinant zoster vaccine dose 1 but not dose 2.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"859-867"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Fetal Exposure to Teratogenic Medications: Development of Evidence for the Teratogenic Risk Impact and Mitigation (TRIM) Tool.","authors":"Yanning Wang, Celeste L Y Ewig, Nicole E Smolinski, Gita A Toyserkani, Cynthia LaCivita, Esther H Zhou, Gerald J Dal Pan, Thuy Nhu Thai, Judith C Maro, Sonja A Rasmussen, Almut G Winterstein","doi":"10.1007/s40264-026-01653-x","DOIUrl":"10.1007/s40264-026-01653-x","url":null,"abstract":"<p><strong>Introduction: </strong>Preventing fetal exposure to teratogenic medications is a public health priority. The Teratogenic Risk Impact Mitigation (TRIM) tool has been developed to support regulatory decisions regarding risk mitigation programs. One of the explicit TRIM criteria requires medication-specific quantification of fetal exposure risk.</p><p><strong>Objective: </strong>To develop and compare population-based estimates of fetal exposure risk for medications with known teratogenicity.</p><p><strong>Methods: </strong>This retrospective US population-based cohort study used claims data from Medicaid and MarketScan^® databases from 01/2014 to 12/2018. Data were analyzed from 12/2023 to 12/2024. We included female patients aged 12-55 years with ≥ 1 teratogenic medication prescription. A validated algorithm identified pregnancies that ended with a live or non-live outcome among medication users. We estimated the fetal exposure rate as the number of pregnancies per at-risk medication exposure time, accounting for teratogenic risk profiles (e.g., ACE inhibitors exert risk in 2nd/3rd trimesters). Rates were averaged across databases to generate tertiles of high/medium/low fetal exposure risk.</p><p><strong>Results: </strong>Among 59,815,213 female enrollees (31,905,714 Medicaid; 27,909,499 MarketScan), 12,819,073 used ≥ 1 teratogenic medication. Fetal exposure rates ranged from 0-1512 per 1000 user-years (tertiles: 2.9 and 11.5), with higher rates observed in Medicaid. Medications that exhibited high rates included fluconazole (1512/1000 user-years, 95% CI 1504.5-1518.6) and sulfamethoxazole/trimethoprim (295, 95% CI 233.6-492.2), vedolizumab (53, 95% CI 46.7-60.2) and several anticonvulsants. Two medications, phentermine-topiramate, with a current risk mitigation program, and fingolimod, with a released risk management program, were also ranked in the highest tertile. Fetal exposures to medications prescribed for acute conditions occurred more frequently through initiation during pregnancy, while those for chronic medications occurred mostly because of conception during treatment.</p><p><strong>Conclusions: </strong>Fetal exposure risks differed across medications and populations, influenced by treatment chronicity, relevant teratogenic risk periods, and patient demographics, which can inform the development of risk mitigation programs. Data gleaned from this analysis will be used as an ordinal \"fetal exposure risk\" criterion score in our development of the TRIM decision tool.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"815-827"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QT Prolongation Risk of Antibody-Drug Conjugates.","authors":"Xu Steven Xu, Kinjal Sanghavi, Summer Feng, Sihang Liu, Jeff Barrett, Manish Gupta","doi":"10.1007/s40264-026-01656-8","DOIUrl":"10.1007/s40264-026-01656-8","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have emerged as an important therapeutic class in oncology, offering targeted delivery of potent cytotoxic agents to cancer cells, thereby reducing systemic toxicity. However, the potential for cardiac toxicity, particularly QT interval prolongation, remains a critical safety concern during ADC development and clinical use. We review the mechanisms underlying ADC-induced QT prolongation, including payload-related direct ion channel interactions and indirect effects mediated by systemic exposure. By systematically examining clinical and preclinical data across ADC classes, including auristatins, maytansinoids, topoisomerase inhibitors, and DNA alkylators, we highlight the risk evaluation of 14 US Food and Drug Administration-approved ADCs, along with their regulatory review outcomes and labeling recommendations. Most approved ADCs appear to have a low corrected QT prolongation risk at therapeutic doses; clear signals are largely confined to inotuzumab and gemtuzumab ozogamicin, whereas auristatin-, maytansinoid-, and topoisomerase-1-based ADCs have shown minimal or no corrected QT changes. Regulatory approaches to ADC QT assessment are flexible and largely driven by payload novelty: novel payloads generally require comprehensive non-clinical testing and early dedicated QT studies, whereas established payloads can often rely on prior safety data, permitting extrapolation without new QT studies and use of pooled clinical data plus concentration-QT analyses when exposure and the linker-payload structure align with historical experience. Finally, we outline a practical framework for integrating translational and regulatory considerations for evaluating QT interval prolongation risk into the development of ADCs for patients with cancer, aiming to enhance cardiac safety for patients and improve the design of preclinical and clinical studies.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"775-796"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical Appraisal of Artificial Intelligence for Rare-Event Recognition: Principles and Pharmacovigilance Case Studies.","authors":"G Niklas Norén, Eva-Lisa Meldau, Johan Ellenius","doi":"10.1007/s40264-026-01649-7","DOIUrl":"10.1007/s40264-026-01649-7","url":null,"abstract":"<p><p>Many high-stakes artificial intelligence (AI) applications target low-prevalence events, where apparent accuracy can conceal limited real-world value. Relevant AI models range from expert-defined rules and traditional machine learning to generative large language models (LLMs) constrained for classification. As the effort and expertise required to develop modern AI decrease, there is a risk that organizations devote too little time to understanding their limitations and sources of error. We outline key dimensions for critical appraisal of AI in rare-event recognition, including problem framing and test set design, prevalence-aware statistical evaluation, robustness assessment, and integration into human workflows. In addition, we propose an approach to structured case-level examination (SCLE), to complement statistical performance evaluation, and a set of considerations to guide procurement or development of AI models for rare-event recognition. We instantiate the framework in pharmacovigilance, drawing on three studies: rule-based retrieval of pregnancy-related reports, duplicate detection combining machine learning with probabilistic record linkage, and automated redaction of person names using an LLM. We highlight pitfalls specific to the rare-event setting including optimism from unrealistic class balance and lack of difficult positive controls in test sets-and show how cost-sensitive targets align model performance with operational value. While grounded in pharmacovigilance practice, the principles generalize to domains where positives are scarce, and error costs may be asymmetric.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"747-760"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Perspective on the Evolution and Future of Pharmacovigilance: Deliverables from the 24th Annual Meeting of the International Society of Pharmacovigilance Celebrating 25 Years of Excellence.","authors":"Mohamed A Elhawary, Brian Edwards, Hadir Rostom, Shanthi N Pal, Viola Macolic Sarinic, Priya Bahri, Deirdre McCarthy, Victoria Prudence Nambasa, Linda Härmark, Andrew Bate, Rebecca Chandler, Marco Tuccori, Fawaz Alharbi, Mohammed Fouda, Comfort Ogar, Jürgen Beckmann, Jayesh Pandit, Mayada Alkhakany, Christina Saad, Manal M Younus, Ivor Ralph Edwards, Omar Aimer","doi":"10.1007/s40264-026-01680-8","DOIUrl":"10.1007/s40264-026-01680-8","url":null,"abstract":"","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"733-745"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically Informed Research Designs in Perinatal Pharmacoepidemiology: A Methodological Overview.","authors":"Alexis C Carson, Mahmoud Zidan, Emilie Willoch Olstad, Kristina Gervin, Tessel E Galesloot, Iris Scholte, Eivind Ystrøm, Hedvig Nordeng, Marleen M H J van Gelder","doi":"10.1007/s40264-026-01647-9","DOIUrl":"10.1007/s40264-026-01647-9","url":null,"abstract":"<p><p>Despite the widespread use of medications during pregnancy, ethical and methodological barriers to clinical trials make observational studies necessary for evaluating medication safety in this population. Observational studies are prone to biases that often limit their validity due to the lack of randomization; integrating genetic information through discordant sibling designs, polygenic scores, and Mendelian randomization can address several confounding issues. However, application of these three approaches in perinatal pharmacoepidemiology has been limited. Complementing traditional designs with these genetically informed research designs can tackle common biases and strengthen causal inference. This paper focuses on applying genetically informed research designs to child outcomes in perinatal pharmacoepidemiology by reviewing various methods, discussing their strengths and limitations, and examining their application to date, as well as considerations for implementing them in future research. Such considerations include the availability of genetic data, the complexity of integrating genetic data with existing epidemiological data, and selection of appropriate genetic instruments for analyses. Incorporating causal inference in perinatal pharmacoepidemiology can ultimately contribute to enhancing safe medication use during pregnancy.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"761-773"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}