Drug Safety最新文献

{"title":"Systematic Evaluation of Australian Risk Management Plans for Biologic Medicines.","authors":"Jun Ni Ho, Jodie Belinda Hillen, Benjamin Daniels, Renly Lim, Nicole Pratt","doi":"10.1007/s40264-025-01557-2","DOIUrl":"10.1007/s40264-025-01557-2","url":null,"abstract":"<p><strong>Background: </strong>Risk management plans (RMPs) are a critical element of pharmacovigilance. However, few studies have examined the quality and type of information included in RMPs, and none has examined the RMPs in the Australian medicines regulatory context.</p><p><strong>Objectives: </strong>This study aims to characterise safety concerns, particularly missing information listed in the current Australian RMPs for commonly used biologic medicines, and identify additional pharmacovigilance and risk minimisation activities proposed to address identified gaps.</p><p><strong>Methods: </strong>A descriptive review of RMPs included in the Australian Public Assessment Reports (2009-2024) was performed for 15 biologic medicines approved for use and universally funded in Australia for inflammatory arthropathies, inflammatory bowel diseases and inflammatory skin conditions. We extracted and quantified safety concerns (important identified risks, important potential risks and missing information) from the latest Australian Public Assessment Reports, and further categorised missing information by specific populations and conditions. We then qualitatively described the additional activities proposed.</p><p><strong>Results: </strong>There were 246 safety concerns listed for the 15 medicines of interest: 85 important identified risks (34.6%), 81 important potential risks (32.9%) and 80 instances of missing information (32.5%). More than half (n = 9, 60%) of the reviewed medicines listed children and adolescents as the most common populations with missing information. Pregnant women (n = 8, 53%) and those with hepatic and renal impairment (n = 7, 47%) were also commonly listed as having missing information. Additional pharmacovigilance activities were proposed for two thirds of the medicines (n = 10, 77%) where missing information was listed. Only one third of the reviewed medicines (n = 5, 33%) had specific proposals or protocols listed in the current Australian Public Assessment Reports to address missing information.</p><p><strong>Conclusions: </strong>Our study identified important gaps in RMPs for commonly used biologic medicines at the post-market phase. Despite some medicines having an extensive market history, these safety concerns remain unaddressed. Regular monitoring and critical review of RMPs are recommended to prioritise post-market studies and address outstanding safety concerns.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1063-1072"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191652","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 Minimisation Measures of Advanced Therapy Medicinal Products Authorised in the EU Between 2009 and 2023: A Cross-Sectional Study.","authors":"Sharon C M Essink, Inge M Zomerdijk, Sabine M J M Straus, Helga Gardarsdottir, Marie L De Bruin","doi":"10.1007/s40264-025-01550-9","DOIUrl":"10.1007/s40264-025-01550-9","url":null,"abstract":"<p><strong>Introduction: </strong>Because of the novelty of advanced therapy medicinal products (ATMPs), pro-active risk management is needed post-authorisation; for example, through implementation of additional risk minimisation measures (aRMMs).</p><p><strong>Objective: </strong>We described which aRMMs were introduced at marketing authorisation (MA) for ATMPs authorised in the European Union (EU), and for what safety concerns.</p><p><strong>Methods: </strong>We included all ATMPs ever authorised in the EU until December 31, 2023. Data on safety concerns and aRMMs was collected from the European public assessment reports (EPARs) related to initial MA for each ATMP. Safety concerns were categorised using the Medical Dictionary for Regulatory Activities (MedDRA^®) or context of use, where appropriate.</p><p><strong>Results: </strong>Of the 25 included ATMPs, most (n = 23, 92.0%) were authorised with aRMMs. Of these 23 ATMPs, all (100%) had educational material for healthcare professionals. Additionally, educational material for patients/caregivers was in place for 18 (78.3%) ATMPs and a controlled distribution or controlled access programme for 16 (69.6%). Safety concerns related to 'Long term effects' (n = 23, 92.0%), 'Injury, poisoning and procedural complications' (n = 22, 88.0%), and 'Use in special populations' (e.g., use in pregnancy) (n = 20, 80.0%) were common among all 25 ATMPs. ATMPs often had aRMMs introduced that addressed safety concerns related to 'Injury, poisoning and procedural complications' (n = 19/23; 82.6%), 'General disorders and administration site conditions' (n = 8, 34.8%), and/or 'Immune system disorders' (n = 8, 34.8%).</p><p><strong>Conclusion: </strong>The majority of ATMPs were authorised with aRMMs. Whilst educational materials were most prevalent, controlled distribution or controlled access programmes were also commonly introduced. For many ATMPs, aRMMs addressed risks related to 'Injury, poisoning and procedural complications'.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1005-1022"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988062","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":"Interplay of Spontaneous Reporting and Longitudinal Healthcare Databases for Signal Management: Position Statement from the Real-World Evidence and Big Data Special Interest Group of the International Society of Pharmacovigilance.","authors":"Salvatore Crisafulli, Andrew Bate, Jeffrey Stuart Brown, Gianmario Candore, Rebecca E Chandler, Tarek A Hammad, Samantha Lane, Judith Christina Maro, G Niklas Norén, Antoine Pariente, Mulugeta Russom, Maribel Salas, Andrej Segec, Saad Shakir, Andrea Spini, Sengwee Toh, Marco Tuccori, Eugène van Puijenbroek, Gianluca Trifirò","doi":"10.1007/s40264-025-01548-3","DOIUrl":"10.1007/s40264-025-01548-3","url":null,"abstract":"<p><p>Signal management, defined as the set of activities from signal detection to recommendations for action, is conducted using different data sources and leveraging data from spontaneous reporting databases (SRDs), which represent the cornerstone of pharmacovigilance. However, the exponentially increasing generation and availability of real-world data collected in longitudinal healthcare databases (LHDs), along with the rapid evolution of artificial intelligence-based algorithms and other advanced analytical methods, offers a wide range of opportunities to complement SRDs throughout all stages of signal management, especially signal detection. Integrating information derived from SRDs and LHDs may reduce their respective limitations, thus potentially enhancing post-marketing surveillance. The aim of this position statement is to critically evaluate the complementary role of SRDs and LHDs in signal management, exploring the potential benefits and challenges in integrating information coming from these two data sources. Furthermore, we presented successful cases of the interplay between SRDs and LHDs for signal management, along with future opportunities and directions to improve such interplay.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"959-976"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972875","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":"Incretin-Based Drugs and the Incidence of Endometrial Cancer Among People with Type 2 Diabetes: Active Comparator New-User Design.","authors":"Sonny M Rothman, Hui Yin, Oriana H Y Yu, Michael Pollak, Laurent Azoulay","doi":"10.1007/s40264-025-01551-8","DOIUrl":"10.1007/s40264-025-01551-8","url":null,"abstract":"<p><strong>Introduction: </strong>The use of incretin-based drugs may be associated with a decreased risk of endometrial cancer among women with type 2 diabetes.</p><p><strong>Methods: </strong>Using data from the UK Clinical Practice Research Datalink and linked databases, two new-user active comparator cohorts of women with type 2 diabetes who initiated glucagon-like peptide 1 receptor agonists (GLP-1 RAs) or sulfonylureas (cohort 1) and DPP-4 inhibitors or sulfonylureas (cohort 2) were assembled. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident endometrial cancer.</p><p><strong>Results: </strong>Cohort 1 included 9239 new users of GLP-1 RAs and 80,086 new users of sulfonylureas. The GLP-1 RAs were not associated with a decreased risk of endometrial cancer when compared with sulfonylureas (HR: 1.11, 95% CI: 0.66-1.88). In a duration-response secondary analysis, use of GLP-1 RAs for more than two years was associated with an increased risk of endometrial cancer (HR: 2.47, 95% CI: 1.37-4.43) when compared to sulfonylureas When analysed by drug type, exenatide was associated with an elevated risk when compared to sulfonylureas (HR: 2.26, 95% CI:1.06-4.82). Cohort 2 included 42,486 new users of DPP-4 inhibitors and 79,353 new users of sulfonylureas. DPP-4 inhibitors were not associated with a decreased risk of endometrial cancer compared with sulfonylureas (HR: 1.00, 95% CI: 0.76-1.32). In a duration-response secondary analysis, use of DPP-4 inhibitors for more than two years was associated with an increased risk of endometrial cancer (HR: 1.63, 95% CI: 1.14-2.33) when compared to sulfonylureas.</p><p><strong>Conclusions: </strong>In this population-based study, the use of GLP-1 RAs and DPP-4 inhibitors was not associated with a decreased risk of endometrial cancer when compared with the use of sulfonylureas among women with type 2 diabetes.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1023-1033"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985755","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":"Evaluation of Data Quality and Utility of the Japan Drug Information Institute in Pregnancy (JDIIP) Consultation Case Database for Pregnancy Pharmacovigilance.","authors":"Shinichi Matsuda, Naho Yakuwa, Mikako Goto, Manabu Akazawa, Kunihiko Takahashi, Tatsuhiko Anzai, Sachi Koinuma, Izumi Fujioka, Yoriko Miura, Mihoko Ota, Hiroaki Oka, Naoki Nitani, Tomiko Tawaragi, Atsuko Murashima","doi":"10.1007/s40264-025-01554-5","DOIUrl":"10.1007/s40264-025-01554-5","url":null,"abstract":"<p><strong>Introduction: </strong>Ensuring medication safety during pregnancy is crucial for protecting maternal and fetal health. However, fragmented data sources and the lack of comprehensive databases present substantial barriers to effective pharmacovigilance. The Japan Drug Information Institute in Pregnancy (JDIIP) database, which contains data on drug treatment counseling for pregnant women, is expected to help address the lack of comprehensive databases for pregnancy pharmacovigilance (PregPV).</p><p><strong>Objective: </strong>We evaluated the quality and utility of the JDIIP database for PregPV activities, particularly its ability to consolidate and utilize drug-exposure data among pregnant women in Japan.</p><p><strong>Methods: </strong>To assess the quality and utility of the JDIIP database for PregPV, we examined its alignment with 48 core data elements (CDEs) considered critical for PregPV, as recently proposed by a European Union consortium through the ConcePTION Project. We performed a detailed mapping of each CDE definition-including maternal lifestyle factors, drug exposure, and pregnancy outcomes-against the corresponding data elements captured in the JDIIP database.</p><p><strong>Results: </strong>The JDIIP database either directly collected or could derive 38 of the 48 specific items (79%) recommended by the ConcePTION Project. At the category level, the JDIIP database aligned closely with the CDE requirements for database management details, pregnancy details, maternal medical history, pregnancy medication exposure, live/stillborn birth outcomes, and malformation details, achieving coverage of over 80% of the necessary variables in each category. Some categories, such as maternal medical conditions arising during pregnancy and infant complications within the first year of life, showed less alignment, with coverage rates below 50%. Although the JDIIP database provides comprehensive coverage of critical pharmacovigilance elements, data collection for specific variables and categories that better align with the CDE framework can be enhanced to improve alignment with the CDE framework and strengthen pharmacovigilance capabilities.</p><p><strong>Conclusions: </strong>Our findings highlight the potential of the JDIIP database as a valuable resource for advancing PregPV research. Although the collection of certain maternal and infant data elements could be improved, the substantial alignment of the database with established CDEs positions it as a promising tool for advancing PregPV initiatives in Japan.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1035-1046"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076679","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":"Characteristics of Drug-RElated Hospitalizations for Nursing HOme Residents: Cross-Sectional RENHO Study.","authors":"Alice Lopez, Chiara Alfarano, Marianne Lepetit, Leila Chebane, Nassima Redjimi, Anaïs Couret, Didier Fabre, Virginie Gardette, Driss Berdaï, Maryse Lapeyre-Mestre, Haleh Bagheri","doi":"10.1007/s40264-025-01556-3","DOIUrl":"10.1007/s40264-025-01556-3","url":null,"abstract":"<p><strong>Background: </strong>Nursing home residents with advancing age are often exposed to polypharmacy, a well-known risk factor for adverse drug reactions (ADRs), which increases the risk of hospitalization. Therefore, we assessed the characteristics of and factors associated with ADR-related emergency department (ED) admissions among nursing home residents.</p><p><strong>Methods: </strong>We carried out a cross-sectional study using the Toulouse University Hospital discharge database to identify nursing home residents ED admissions from 1 April, 2019 to 31 March, 2020. Information was updated for 2 years after inclusion (re-admissions). Emergency department medical files were analyzed to identify factors associated with these admissions (including demographics, functional dependency level, comorbidities, body mass index, ED admission in the previous 12 previous months, and number of drugs).</p><p><strong>Results: </strong>We identified 1514 patients (corresponding to 2024 ED admissions), 409 of whom (27.0%) were admitted at least once for an ADR. Thirty-six nursing home residents were re-admitted in 2020 and/or 2021 for ADRs, half of whom were for the same ADR. The most frequent ADRs were falls (114, 24.3%), hemorrhagic events (106, 22.6%), and constipation (47, 10.0%) involving benzodiazepines and Z-drugs (170, 16.0%), antidepressants (125, 11.9%), antithrombotic drugs (110, 10.3%), and opioids (82, 7.7%). About 12% of ADRs were assessed as avoidable. Factors significantly associated with ADR-related ED admissions were the number of drugs (odds ratio 1.09; 95% confidence interval 1.05-1.13), previous ED admissions (odds ratio 3.47; 95% confidence interval 2.46-4.90), and overweight (odds ratio 1.54; confidence interval 1.15-2.06).</p><p><strong>Conclusions: </strong>Drug-induced iatrogenic disease could lead to ED admission for nursing home residents in approximately one-quarter of cases, 12% of which were assessed as avoidable. A previous history of ED admission and polypharmacy remain key associated factors. The awareness-raising campaigns for health professionals should be strengthened to prevent avoidable drug-induced ADRs.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"1047-1061"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526909","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":"Impact of Batoclimab Treatment on LDL-C with and Without Coadministration of Atorvastatin: Results from a Phase I Randomized Study in Healthy Participants.","authors":"Thomas Hardy, Su Liang, Philip Tedeschi, E Lin, Eliot A Brinton, Michael H Davidson","doi":"10.1007/s40264-025-01549-2","DOIUrl":"10.1007/s40264-025-01549-2","url":null,"abstract":"<p><strong>Introduction: </strong>Batoclimab is an anti-neonatal fragment crystallizable receptor monoclonal antibody in clinical development for the treatment of autoimmune diseases. In phase II trials, batoclimab resulted in dose-dependent reductions in pathogenic immunoglobulin G autoantibodies; however, dose-related increases in low-density lipoprotein cholesterol and other lipids were observed.</p><p><strong>Objective: </strong>This study examined the relationship between batoclimab treatment and lipid levels, and whether increases in low-density lipoprotein cholesterol could be mitigated by coadministration with atorvastatin, a widely used cholesterol-lowering agent.</p><p><strong>Methods: </strong>In this phase I, randomized, fixed-sequence, single-blind trial, 70 healthy participants received subcutaneous injections of batoclimab at various doses or placebo for 6 weeks. Open-label oral atorvastatin was coadministered in a subset of participants receiving batoclimab 340 mg or 680 mg weekly, starting 14 days before the first dose of the study drug, and continuing through the 6-week treatment period and 8-week safety follow-up. Key endpoints included changes in lipid parameters and atorvastatin pharmacokinetics.</p><p><strong>Results: </strong>Dose-dependent increases in total cholesterol and low-density lipoprotein cholesterol were observed with batoclimab doses ≥ 255 mg weekly, comparable to previous observations, whereas coadministration of atorvastatin 10 mg or 40 mg daily mitigated these changes. Batoclimab had little effect on atorvastatin pharmacokinetics. Dose-dependent decreases in serum albumin up to 37% were observed with batoclimab doses ≥ 255 mg weekly, returning to near-baseline levels 4 weeks after stopping batoclimab. As expected, coadministration of atorvastatin did not meaningfully impact the albumin level. The majority of adverse events were mild in severity.</p><p><strong>Conclusions: </strong>Atorvastatin can mitigate clinically significant increases in low-density lipoprotein cholesterol that may occur with batoclimab treatment.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":"993-1004"},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982662","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":"R Value-Based Criteria Outperform Alkaline Phosphatase Less than Twice Normal in Identifying Hy's Law Cases in Clinical Trials.","authors":"Jasmine Amirzadegan, Edwige Chiogo Vouffo, Ling Lan, Eileen Navarro Almario, Mark I Avigan, Paul H Hayashi","doi":"10.1007/s40264-025-01603-z","DOIUrl":"https://doi.org/10.1007/s40264-025-01603-z","url":null,"abstract":"<p><strong>Background: </strong>It is unknown whether nR value [(ALT or AST/ULN) ÷ (AP/ULN)] ≥ 5 is better than alkaline phosphatase less than twice the upper limit of normal (AP < 2x ULN) in identifying hepatocellular drug-induced liver injury (HC DILI) consistent with Hy's law in clinical trials.</p><p><strong>Objective: </strong>We aimed to compare nR value ≥ 5 and AP < 2x ULN in clinical trial DILI cases with ALT or AST ≥ 3x ULN and total bilirubin (TB) > 2x ULN.</p><p><strong>Methods: </strong>We retrospectively categorized clinical trial, DILI cases from July 2020 to April 2024 with ALT or AST ≥ 3x ULN and jaundice as meeting nR value ≥ 5, AP < 2x ULN, both, or neither. We determined positive predictive values (PPVs) and sensitivities for HC DILI-related fatality (death or liver transplant) and acute liver failure (ALF).</p><p><strong>Results: </strong>Of 1314 liver injuries across 73 drug applications, 294 (22%) were attributed to DILI; 55 had ALT or AST ≥ 3x ULN and TB > 2x ULN. We excluded three cases (Gilbert's, high baseline enzymes, hepatitis B reactivation). Of 52 remaining, 16 (31%) met nR ≥ 5, five (10%) AP < 2x ULN, 21 (40%) both, and 10 (19%) neither. There were four DILI fatalities. Excluding one cholestatic fatality, nR ≥ 5 and AP < 2x ULN had PPVs for HC DILI fatality of 8 and 4%, respectively; sensitivities were 100 and 33%, respectively. One patient survived HC DILI-related ALF. Including this ALF case with the fatalities, nR ≥ 5 and AP < 2x ULN had PPVs of 11 and 4%, respectively; sensitivities were 100 and 25%, respectively. All fatalities and ALF cases were due to different drugs.</p><p><strong>Conclusion: </strong>While the number of cases with the most severe DILI outcomes was small, particularly those that resulted in fatalities or ALF, nR ≥ 5 better approximated Hy's Law and was more sensitive than AP < 2x ULN in detecting fatalities and ALF.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946770","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":"External Comparator Studies: Performance of Four Missing Data-Handling Approaches, Stratified by Four Different Marginal Estimators.","authors":"Gerd Rippin, Héctor Sanz, Wilhelmina E Hoogendoorn, Joan A Largent","doi":"10.1007/s40264-025-01586-x","DOIUrl":"https://doi.org/10.1007/s40264-025-01586-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Missing data and unmeasured confounding may bias results of external comparator (EC) studies. Previous research quantified these effects, but there were still knowledge gaps in terms of studying a broader set of missing data-handling approaches. This knowledge gap is addressed by investigating four different ways to handle missing data for a set of four distinct marginal estimators.</p><p><strong>Methods: </strong>An extensive simulation study was conducted based on two real EC case studies. Four different variants of missing data-handling approaches were assessed in terms of bias and other performance characteristics. Specifically, multiple imputation (MI) for the trial and EC cohorts was conducted by applying within-cohort MI, across-cohort MI and a mixed within-across-cohort MI scheme. Dropping a covariate from the analysis model if missingness exceeded a certain threshold was also added as an analysis strategy. All simulation results were generated for a set of four marginal estimators: the average treatment effect of the untreated (ATU), the average treatment effect (ATE), the average treatment effect of the treated (ATT), and the average treatment effect in the overlap population (ATO). Missingness was simulated to occur only in the EC cohort, and propensity score weighting was applied as causal inference method.</p><p><strong>Results: </strong>Overall, within-cohort MI and the ATU showed best performance in terms of mitigating bias, while the strategy of leaving out prognostic factors (covariates) due to a higher percentage of missingness performed worst.</p><p><strong>Conclusions: </strong>Performances of four missing data-handling strategies were assessed for a set of four different marginal estimators. Our results add clarity with regard to potential residual bias for researchers conducting EC studies when using propensity score weighting in the case of missing data or unmeasured confounding. This enables researchers to select most appropriate statistical approaches to minimise bias, potentially by including an additional bias estimation and correction step.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946758","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":"Navigating Medical Device Safety: Current Status, Challenges, and Future Regulatory Directions.","authors":"Omar Aimer, Catherine Baldridge","doi":"10.1007/s40264-025-01599-6","DOIUrl":"https://doi.org/10.1007/s40264-025-01599-6","url":null,"abstract":"<p><p>Medical devices are indispensable in modern healthcare. They enable the prevention, diagnosis, and treatment of diseases while enhancing patient outcomes. However, the increasing complexity of these devices, particularly those incorporating advanced technologies such as artificial intelligence (AI) introduces new challenges to their safe use. The vulnerabilities of medical devices can lead to adverse events ranging from minor complications to severe injuries or fatalities, and there is an increasing health risk to those devices that are interconnected to electronic health management systems and internet protocols. Despite efforts by regulatory authorities such as the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Health Canada, disparities in reporting systems and monitoring practices persist globally, hindering effective safety oversight. This paper explores the current landscape of medical device safety, focusing on regulatory frameworks, reporting systems, and the challenges posed by fragmented data collection and underreporting. It highlights the critical role of postmarket surveillance (PMS) in identifying risks and ensuring device performance in real-world settings. The integration of emerging technologies, such as AI for predictive safety and blockchain for traceability, offers promising solutions to enhance monitoring and mitigate risks early in the device lifecycle. In addition, the paper examines harmonization efforts led by organizations such as The International Medical Device Regulators Forum (IMDRF), the International Society of Pharmacovigilance (ISoP) and the World Health Organazition (WHO), which aim to standardize reporting practices and improve global collaboration. Key recommendations include leveraging real-world data, enhancing cybersecurity measures, and fostering international cooperation to streamline regulatory processes. By addressing these challenges and embracing innovation, stakeholders can ensure that medical devices continue to advance healthcare while maintaining the highest safety standards. Such collective efforts are essential for safeguarding patient trust and improving global health outcomes.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946709","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}