Drug Safety[JOURNAL]
Sun
200 papers
Reporting Adverse Drug Events: A Comparison of an Online Patient Tool Versus Telephone-Based Monitoring in Community Pharmacy Patients in the Netherlands.
Habtemariam HD, Guchelaar HJ, Manson LEN … +3 more , Swen JJ, Kant AC, Böhringer S
Drug Saf · 2025 Nov · PMID 40517185 · Full text
BACKGROUND: Adverse drug events (ADEs) are events occurring after the administration of a drug. Several authorities are involved in capturing these ADEs to improve pharmacovigilance. These ADEs are reported directly to h...
BACKGROUND: Adverse drug events (ADEs) are events occurring after the administration of a drug. Several authorities are involved in capturing these ADEs to improve pharmacovigilance. These ADEs are reported directly to healthcare professionals or via the telephone, online, or e-mail and are crucial for maintaining drug safety. OBJECTIVE: Patient-reported adverse drug events (ADEs) are collected using various tools, though not much is known with regard to the comparability of these different methodologies. It is known that telephone-based surveys result in a higher report rate, although it is not known if this has an effect on the type of ADEs that are reported. In this prospective study, we aimed to investigate if there are differences in the number, type, and severity of ADEs reported via telephone and online in an event monitoring setting. METHODS: Patients included in Dutch community pharmacies were asked whether they experienced any ADEs via telephone and online (Lareb Intensive Monitoring) surveys as part of the PREPARE study. The PREPARE study was a multicenter study, researching the effect of genotype-guided dosing on the incidence of clinically relevant adverse drug reactions. With the paired data acquired in the PREPARE study, we investigated differences in the number, type, and severity of the reported ADEs. RESULTS: Patients (N = 525) completed both the telephone and online surveys. Of the 525 patients who completed both surveys, 326 reported ADEs via telephone and 239 online. A visual comparison showed a similar distribution in the type of ADEs among the methods except for less commonly reported types of ADEs and cardiac disorders. The perceived severity of ADEs were proportionally reported as more severe during the telephone survey versus the online survey. CONCLUSIONS: Our study showed a clear difference in the number of ADEs reported during telephone and online monitoring. Additionally, the differences in the type of ADEs and the severity distribution of both tools shows that the tools are not exchangeable (CT.gov identifier: NCT03093818).
Identifying Maternal Conditions Leading to Gabapentinoid Prescriptions in Pregnancy Using Electronic Health Records from Six European Countries: A Contribution from the IMI ConcePTION Project.
Beau AB, Paoletti O, Bénévent J … +21 more , Beslay M, Moisset X, Ballardini E, Barrachina-Bonet L, Cavero-Carbonell C, Coldea A, García-Villodre L, Geldhof A, Gini R, Gissler M, Jordan S, Leinonen MK, Manfrini M, Martikainen V, Mitter VR, Morris JK, Neville AJ, Nordeng H, Puccini A, Mo J, Damase-Michel C
Drug Saf · 2025 Nov · PMID 40514582 · Full text
INTRODUCTION AND OBJECTIVE: Given the recent increase in the prescription and dispensation of gabapentinoids (gabapentin and pregabalin) and the importance of controlling for underlying maternal illnesses in drug safety...
INTRODUCTION AND OBJECTIVE: Given the recent increase in the prescription and dispensation of gabapentinoids (gabapentin and pregabalin) and the importance of controlling for underlying maternal illnesses in drug safety studies, we aimed to develop algorithms for identifying maternal conditions leading to gabapentinoid prescribing among pregnant women using data from six electronic healthcare data sources across Europe. METHODS: The study was conducted in Finland, France (Haute-Garonne), Italy (Emilia Romagna), Norway, Spain (Valencian region), and Wales (UK), covering three million pregnancies from 2006 to 2020. Algorithms were developed to detect epilepsy, neuropathic pain, and generalized anxiety disorder (GAD) (approved indications for gabapentinoids by the European Medicines Agency, with the exception of gabapentin for GAD) using data ± 1 year around the gabapentinoid prescription date. Data included prescriber specialty, primary and specialized health care diagnoses, and co-prescription/dispensation data. Additional analyses investigated potential unlicensed indications (such as fibromyalgia, restless legs syndrome, bipolar disorder) and potential for abuse (using codes for substance use disorders and alcohol withdrawal). RESULTS: Gabapentinoids were prescribed/dispensed in 1770 pregnancies (7.7 per 1000) in Spain, 2912 pregnancies (6.6 per 1000) in Wales, 3163 pregnancies (3.6 per 1000) in Norway, 2406 pregnancies (3.0 per 1000) in Finland, 908 pregnancies (2.2 per 1000) in Italy, and 269 pregnancies (1.9 per 1000) in France. A maternal condition related to gabapentinoid prescriptions was identified by the algorithm in 2797 (88.4%) in Norway, 2180 (74.9%) in Wales, 1269 (71.7%) in Spain, 1534 (63.8%) in Finland, 163 (60.6%) in France, and 396 (43.6%) pregnancies in Italy. Anxiety (licensed or unlicensed) was the most commonly captured condition in Wales (70.5%), Spain (51.5%), Finland (42.0%), and Italy (26.2%), whereas neuropathic pain prevailed in Norway (76.9%) and France (49.8%). Epilepsy was the least frequent maternal condition leading to gabapentinoid prescriptions across all data sources (below 15% of all pregnancies). The relative preponderance of these conditions differed between pregabalin and gabapentin. Additionally, unlicensed indications were captured in 0% to 13% of pregnancies, depending on the data source. The analyses of potential for abuse showed that records of alcohol withdrawal and/or substance use disorders (within 1 year before and after the gabapentinoids prescription/dispensation date) were present in 3% of pregnancies in Italy and up to 23% in Wales. CONCLUSIONS: Our study provides valuable insights into gabapentinoid use during pregnancy, with anxiety being the most common condition among pregnant women with gabapentinoid prescriptions in Finland, Italy, Spain, and Wales, whereas neuropathic pain predominated in France and Norway. Moreover, we found that between 3 and 23% of these pregnancies were associated with substance abuse, underscoring the need for careful prescribing of commonly abused medicines. The proposed methods for detecting maternal conditions leading to prescribing will facilitate accurate assessment of medication use and safety during pregnancy, whilst addressing confounding by indication.
Investigation of Ochratoxin A and Citrinin Occurrence in Medicinal Herbal Products from the Czech Market.
Toman J, Pickova D, Brandova K … +2 more , Ostry V, Malir F
Drug Saf · 2025 Nov · PMID 40506653 · Publisher ↗
INTRODUCTION: Medicinal plants are extensively utilized as dietary supplements to encourage disease prevention and to support the treatment of various health disorders. Unfortunately, several plants are known for mycotox...
INTRODUCTION: Medicinal plants are extensively utilized as dietary supplements to encourage disease prevention and to support the treatment of various health disorders. Unfortunately, several plants are known for mycotoxin contamination, which may overwhelm any beneficial effects the plants might have. OBJECTIVE: The purpose of the study was to determine the presence of ochratoxin A (OTA) and citrinin (CIT) in medicinal herbal products (MHP). METHODS: Sixty samples of different MHP types were purchased on the Czech market during 2020-2021. Both mycotoxins were determined using high-performance liquid chromatography with a fluorescence detector with immunoaffinity columns employed as a pretreatment. RESULTS: In total, 40% and 27% of samples were above the limit of quantification with the concentrations ranging up to 826.62 ng/g and 472.79 ng/g for OTA and CIT, respectively. The co-occurrence was confirmed in six MHP types. CONCLUSIONS: MHP could be a significant source of OTA and CIT. To protect the health of MHP users, it is desirable to continue monitoring the presence of mycotoxins in MHP. During this study, new OTA regulations for herbs came into force in the EU.
Comparison of Adverse Events in Pregnant Persons Receiving COVID-19 and Influenza Vaccines: A Disproportionality Analysis Using Combined Data from US VAERS and EudraVigilance Spontaneous Report Databases.
Roque-Pereira L, Sisay MM, Ogar CK … +5 more , Durán CE, van Puijenbroek E, Weibel D, Verhamme K, Sturkenboom M
Drug Saf · 2025 Oct · PMID 40495022 · Full text
BACKGROUND: Although multiple post-licensure studies demonstrated that coronavirus disease-2019 (COVID-19) vaccines are safe for use during pregnancy, none of them have identified a signal of disproportionate reporting....
BACKGROUND: Although multiple post-licensure studies demonstrated that coronavirus disease-2019 (COVID-19) vaccines are safe for use during pregnancy, none of them have identified a signal of disproportionate reporting. AIM: To assess the disproportionality in reported adverse events among pregnant persons receiving COVID-19 vaccination compared with influenza vaccines in spontaneous reporting databases. METHODS: Individual case safety reports (ICSRs) with COVID-19 vaccines (Pfizer, AstraZeneca, Moderna and Johnson & Johnson) and influenza vaccines were retrieved from spontaneous reporting databases in the Vaccine Adverse Event Report System (VAERS) and the EudraVigilance (EV) system between 1 December 2020 and 31 October 2023. Both datasets were combined through a common data model. Pregnancy-associated ICSRs were identified using adaptations to the European Medicines Agency (EMA) algorithm based on age groups and key medical conditions. We compared the disproportionate reporting of High-Level Terms (HLT) after COVID-19 vaccines of interest (e.g. mRNA vaccine) with another COVID-19 viral vector-based/protein subunit and influenza vaccines during pregnancy. The proportional reporting ratio (PRR) with 95% confidence intervals (CIs) was calculated using a combined dataset. PRR met the predefined criteria (PRR ≥ 2, lower 95% CI ≥ 2 and N ≥ 3), confirming a potential signal of disproportionate reporting (SDR). RESULTS: A total of 22,383 pregnancy-related ICSRs were included. Five associations met the PRR threshold: inborn errors of steroid synthesis 35.1 (95% CI 7.8-158.3); non-site-specific embolism and thrombosis 15.9 (95% CI 3.1-82.2); general signs and symptoms not elsewhere classified (NEC) 11.17 (95% CI 3.3-38.1); peripheral nervous system disorders congenital NEC 4.2 (95% CI 2.3-7.7); and vascular anomalies congenital NEC 3.7 (95% CI 2.4-5.6), all associated with viral vector-based/protein subunit. CONCLUSIONS: Despite this analysis, several statistical disproportionalities were identified during pregnancy; the case-by-case analysis shows that embolism and thrombosis require prioritized investigation through proper causal inference studies.
Comment on "Drug-Induced Cognitive Impairment".
Ben Salem C
Drug Saf · 2025 Jul · PMID 40481937 · Publisher ↗
Abstract loading — click title to view on PubMed.
Authors' reply to Chaker Ben Salem's comment on: "Drug-Induced Cognitive Impairment".
Reimers A, Odin P, Ljung H
Drug Saf · 2025 Jul · PMID 40481936 · Publisher ↗
Abstract loading — click title to view on PubMed.
Large-scale Empirical Identification of Candidate Comparators for Pharmacoepidemiological Studies.
Bohn J, Gilbert JP, Knoll C … +2 more , Kern DM, Ryan PB
Drug Saf · 2025 Nov · PMID 40467833 · Full text
BACKGROUND AND OBJECTIVE: The new user cohort design has emerged as a best practice for the estimation of drug effects from observational data. However, despite its advantages, this design requires the selection and eval...
BACKGROUND AND OBJECTIVE: The new user cohort design has emerged as a best practice for the estimation of drug effects from observational data. However, despite its advantages, this design requires the selection and evaluation of comparators for appropriateness, a process that can be challenging. The objective of this work was to introduce an empirical approach to rank candidate comparators in terms of their similarity to a target drug in high-dimensional covariate space. METHODS: We generated new user cohorts for each RxNorm ingredient and Anatomic Therapeutic Chemical level 4 class in five administrative claims databases then extracted aggregated pre-treatment covariate data for each cohort across five clinically oriented domains. We formed all pairs of cohorts with ≥ 1000 patients and computed a scalar similarity score, defined as the average of cosine similarities computed within each domain, for each pair. We then generated ranked lists of candidate comparators for each cohort. RESULTS: Across up to 1350 cohorts forming 922,761 comparisons, drugs that were more similar in the Anatomic Therapeutic Chemical hierarchy had higher cohort similarity scores. The most similar candidate comparators for each of six example drugs corresponded to alternative treatments used in the target drug's indication(s), and choosing the top-ranked comparator for randomly selected drugs tended to produce balance on most covariates. This approach also ranked highly those comparators chosen in high-quality published new user cohort design studies. CONCLUSION: Empirical comparator recommendations may serve as a useful aid to investigators and could ultimately enable the automated generation of new user cohort design-derived evidence, a process that has previously been limited to self-controlled designs.
An Evaluation of Duplicate Adverse Event Reports Characteristics in the Food and Drug Administration Adverse Event Reporting System.
Janiczak S, Tanveer S, Tom K … +4 more , Zhang R, Ma Y, Wolf L, Muñoz MA
Drug Saf · 2025 Oct · PMID 40467832 · Full text
INTRODUCTION: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) receives duplicate reports of adverse events associated with drug and therapeutic biological products. Duplicate reports, define...
INTRODUCTION: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) receives duplicate reports of adverse events associated with drug and therapeutic biological products. Duplicate reports, defined as multiple reports of the same adverse event(s) related to the administration of the same marketed product(s) to the same individual patient at a particular point in time, may be received in FAERS for many reasons. The presence of duplicate reports can negatively impact public health surveillance efforts by impeding both safety signal identification and signal evaluation. OBJECTIVES: To characterize the features and contributing factors associated with duplicate reports in FAERS. METHODS: We manually assessed a convenience sample of individual case safety reports (ICSRs) for duplication, resulting in two data sets: one consisting of non-duplicate reports and one with duplicate reports. We then compared key features of these two datasets, including both structured and unstructured data fields. Key comparison features included: report and reporter type, country of report origin, data source for report, and outcome. In addition, we evaluated information similarity of reports for seven data elements (e.g., age, sex, suspect products) within sets of duplicates using both structured and unstructured fields. We used pairwise sentence bidirectional encoder representations from transformers (SBERT) cosine similarity scores to examine free-text narrative similarity. RESULTS: Among the 2297 reports in the sample, 901 (39%) were classified as duplicates, consisting of 237 unique duplicate sets. Compared to non-duplicate reports, duplicates were more likely to be foreign reports (82% versus 37%), reported by healthcare professionals (89% versus 68%), mention other regulatory authority databases (42% versus 11%), describe published case reports (34% versus 11%), or have a serious outcome (97% versus 83%) (p < 0.0001). Within sets of duplicates (n = 237), coded information was frequently different, with only 16% (n = 39) having concordance of all 7 data elements. The narrative was highly similar among most sets of duplicates; we found that the median similarity score for the duplicate pairs was 0.87 compared to 0.48 for non-duplicate pairs. CONCLUSIONS: We observed differences in the attributes of and potential contributors to duplicate reports in FAERS that may inform duplicate prevention, detection, and management strategies. However, further studies are needed to better understand the implications of these findings and how potential regulatory changes and technological advances can be leveraged to further address duplicate reporting in adverse event reporting systems.
Systematic Evaluation of Australian Risk Management Plans for Biologic Medicines.
Ho JN, Hillen JB, Daniels B … +2 more , Lim R, Pratt N
Drug Saf · 2025 Sep · PMID 40448798 · Full text
BACKGROUND: 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 Austral...
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Predictive Models for Identifying Adult Patients at High Risk of Developing Opioid-Related Harms: a Systematic Review.
Yismaw MB, Peterson GM, Kefale B … +1 more , Bezabhe WM
Drug Saf · 2025 Nov · PMID 40434632 · Publisher ↗
INTRODUCTION: Opioids are the most frequently prescribed medications for managing moderate-to-severe pain and are associated with significant potential for harm. Several models have been developed to predict opioid-relat...
INTRODUCTION: Opioids are the most frequently prescribed medications for managing moderate-to-severe pain and are associated with significant potential for harm. Several models have been developed to predict opioid-related harms (ORHs). This study aimed to describe and evaluate the methodological quality of predictive models for identifying patients at high risk of ORHs. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, we reviewed published studies on developing or validating models for predicting ORHs, identified through a literature search of Scopus, PubMed, Embase, and Google Scholar. The quality of studies was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). The models were assessed by area under the curve (AUC) or c-statistic, sensitivity, specificity, accuracy, and positive or negative predictive value. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024540456). RESULTS: We included 36 studies involving participants aged 18 years or older. The frequently modeled ORHs were opioid use disorder (12 studies), opioid overdose (8 studies), opioid-induced respiratory depression (6 studies), and adverse drug events (4 studies). In total, 16 studies (44.4%) developed and validated tools. Most studies measured predictive ability using AUC (31, 86.1%), and some only reported sensitivity (14, 38.9%), specificity (11, 30.6%), or accuracy (4, 11.1%). Of the 31 studies that reported AUC values, 29 (93.5%) had moderate-to-high predictive ability (AUC > 0.70). History of opioid use (66.7%), age (58.3%), comorbidities (41.7%), sex (41.7%), and drug abuse and psychiatric problems (36.1%) were typical factors used in developing models. CONCLUSIONS: The included predictive models showed moderate-to-high discriminative ability for screening patients at risk of ORHs. However, future studies should refine and validate them in various settings before considering the translation into clinical practice.
The Role of Adverse Event Follow-Up in Advancing the Knowledge of Medicines and Vaccines Safety: A Scoping Review.
Kara V, Van Hunsel F, Bate A … +1 more , van Puijenbroek E
Drug Saf · 2025 Sep · PMID 40392520 · Full text
INTRODUCTION AND OBJECTIVE: Adverse events (AEs) associated with medication and vaccine use are of significant concern in pharmacovigilance (PV), necessitating robust detection, documentation, and reporting mechanisms. T...
INTRODUCTION AND OBJECTIVE: Adverse events (AEs) associated with medication and vaccine use are of significant concern in pharmacovigilance (PV), necessitating robust detection, documentation, and reporting mechanisms. The primary objective of this scoping review is to understand and evaluate the concept, implementation, frequency, and value of "follow-up" in the context of AE assessment. Secondary objectives include providing an overview of various definitions of "follow-up," describing the requirements and studies evaluating follow-up methods, and assessing how often follow-up is undertaken in assessing an AE, by whom, and its value. METHODS: This scoping review followed the 2018 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews. The protocol was registered on the Open Science Framework (OSF). The review included peer-reviewed literature and regulatory guidelines, the search strategy involved querying MEDLINE (via PubMed) and Embase for publications indexed from January 2013 to December 2023. The Rayyan collaborative review platform was used to manage duplicates and select eligible studies. Data extraction was performed using a standardized template, and the extracted data were summarized descriptively. RESULTS: The search yielded 4,428 articles, with 23 studies meeting the inclusion criteria. Methods for follow-up varied among the studies, with digital tools such as emails, online surveys, and SMS utilized in 22% of the studies, achieving response rates ranging from 29 to 31%. Telephone follow-up was employed in 17% of studies, showing higher response rates between 62 and 89%. In settings with limited digital access, home visits were conducted in 9% of studies; only one study reported a response rate which was 74%. The nature of the follow-up approach was diverse: 35% of studies conducted open-ended follow-up, where no pre-determined AEs were specified, whilst 22% of studies focused on specific AEs or outcomes; the remaining 43% had other reasons such as deduplication, assessing informativeness, characterizing unlisted adverse drug reactions (ADRs) or were related to studies evaluating follow-up methods. The initiation of follow-up activities, including methodological research, was driven by academia in 30% of studies, PV centers in 44%, and marketing authorization holders (MAHs) in 26%. Consent practices varied across the studies: 39% of studies did not pre-consent individuals prior to requesting follow-up, while 31% secured consent to contact prior to follow-up, and the other 30% related to studies evaluating follow-up methods. CONCLUSION: Despite the use of follow-up across all PV organizations, and existing regulatory guidance, there is a dearth of scientific research on the topic. While rates of follow-up were quoted between 19 and 100% there is inconsistency in the use of the term, and huge variability in the way follow-up was studied and the scenarios in which it was studied, constraining the ability to generalize. Further research is needed to determine the optimal types of reports and AEs that benefit most from follow-up, the correlation between the number of questions asked and response rates, and the impact of follow-up information on the evaluability of AE reports.
Risk of New-Onset Atrial Fibrillation in Opioid Users: A Systematic Review and Meta-Analysis on 24,006,367 Participants.
Menichelli D, Gazzaniga G, Pannunzio A … +5 more , Palumbo IM, Pani A, Pignatelli P, Valeriani E, Pastori D
Drug Saf · 2025 Oct · PMID 40383741 · Full text
BACKGROUND: Despite ongoing efforts, the prescription of opioids is still common. Long-term opioid use has been associated with an increased risk of adverse cardiovascular outcomes. OBJECTIVE: We aimed to evaluate the as...
BACKGROUND: Despite ongoing efforts, the prescription of opioids is still common. Long-term opioid use has been associated with an increased risk of adverse cardiovascular outcomes. OBJECTIVE: We aimed to evaluate the association between opioid use and the risk of new-onset atrial fibrillation. METHODS: We performed a systematic review and meta-analysis of studies retrieved from MEDLINE and EMBASE databases according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines from inception to 29 January, 2024. The protocol was registered at PROSPERO (CRD42024512500). Two authors independently screened and extracted data from included studies. The quantitative analysis included only observational studies and results were synthesised by a pooled hazard ratio. Risk of bias was performed according to the ROBINS-I Cochrane tool, and the summary of evidence according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations). RESULTS: Four out of 782 studies met the inclusion criteria for a quantitative analysis with 24,006,367 participants. Overall, 153,734 were opioid users. The proportion of women ranged from 13.2 to 100% and the median age ranged from 34 to 65 years. Studies reported 991,263 cases of new-onset atrial fibrillation. The pooled analysis showed a significant association between use of opioids and new-onset atrial fibrillation (hazard ratio 1.96, 95% confidence interval 1.43-2.69 with high heterogeneity). A sensitivity analysis by removing the study with the largest cohort showed similar results to the main analysis. In the summary of findings, the certainty of the evidence according to GRADE was moderate. CONCLUSIONS: We found a significant association between opioid use and the risk of new-onset atrial fibrillation. When prescribing opioids, the risk of new-onset atrial fibrillation should be considered, especially in the presence of other risk factors for atrial fibrillation.
Evaluation of Data Quality and Utility of the Japan Drug Information Institute in Pregnancy (JDIIP) Consultation Case Database for Pregnancy Pharmacovigilance.
Matsuda S, Yakuwa N, Goto M … +11 more , Akazawa M, Takahashi K, Anzai T, Koinuma S, Fujioka I, Miura Y, Ota M, Oka H, Nitani N, Tawaragi T, Murashima A
Drug Saf · 2025 Sep · PMID 40374964 · Full text
INTRODUCTION: 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 effe...
INTRODUCTION: 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). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Incretin-Based Drugs and the Incidence of Endometrial Cancer Among People with Type 2 Diabetes: Active Comparator New-User Design.
Rothman SM, Yin H, Yu OHY … +2 more , Pollak M, Azoulay L
Drug Saf · 2025 Sep · PMID 40347221 · Publisher ↗
INTRODUCTION: The use of incretin-based drugs may be associated with a decreased risk of endometrial cancer among women with type 2 diabetes. METHODS: Using data from the UK Clinical Practice Research Datalink and linked...
INTRODUCTION: The use of incretin-based drugs may be associated with a decreased risk of endometrial cancer among women with type 2 diabetes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Impact of Batoclimab Treatment on LDL-C with and Without Coadministration of Atorvastatin: Results from a Phase I Randomized Study in Healthy Participants.
Hardy T, Liang S, Tedeschi P … +3 more , Lin E, Brinton EA, Davidson MH
Drug Saf · 2025 Sep · PMID 40287571 · Full text
INTRODUCTION: 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-dependen...
INTRODUCTION: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Atorvastatin can mitigate clinically significant increases in low-density lipoprotein cholesterol that may occur with batoclimab treatment.
A Mixed-Methods Evaluation to Identify Industry Knowledge Needs and Challenges in Health Product Defect and Recall Reporting in Singapore.
Ang PS, Ng MSY, Teo DCH … +6 more , Dorajoo SR, Tan FM, Mai AQ, Ng WGW, Poh JWW, Choong CT
Drug Saf · 2025 Aug · PMID 40272756 · Publisher ↗
INTRODUCTION: Health product defects are complex issues affecting the quality standards of health products and indirectly impact public health outcomes. It is crucial for the pharmaceutical industry to be clear of the re...
INTRODUCTION: Health product defects are complex issues affecting the quality standards of health products and indirectly impact public health outcomes. It is crucial for the pharmaceutical industry to be clear of the reporting and case management requirements for such issues. The Health Sciences Authority of Singapore used a mixed-methods evaluation strategy, combining an online questionnaire and face-to-face focus group discussions to identify areas for knowledge enhancement and challenges faced by the industry regarding product defect reporting and recall procedures. These findings were used to plan training workshops. METHODS: A self-administered online survey was emailed to representatives of all pharmaceutical companies with registered medicines and/or vaccines, or cell, tissue and gene therapy products (CTGTPs) in Singapore. The aim was to find out the challenges faced with product defect reporting and recall procedures. Two face-to-face focus group discussions were conducted with selected companies, specifically those that conducted product recalls between September 2022 and August 2024. A two-day online industry training workshop was held in October 2024. Pre- and post-workshop quizzes, including self-rating questions, were conducted to quantify the participants' baseline knowledge and what they gained from the workshop. RESULTS: In total, 136 out of 463 individuals (29.4%) completed the online survey questionnaire for medicines and vaccines, while 24 out of 42 individuals (57.1%) completed the survey for CTGTPs. Seventeen industry professionals were invited for two focus group discussions. Participants provided feedback on existing processes, and requested clearer guidelines and examples on reportable defects, to aid their internal decision-making. The training workshop saw 318 and 271 industry professionals in attendance over two days, respectively, with 160 participating in both pre- and post-workshop quizzes. There was an improvement in average quiz scores ranging from 4.5% to 25.0% post-workshop. Participants' self-ratings also improved from a median of 3 (out of 5) to median of 4 from pre- to post-workshop. CONCLUSIONS: The series of evaluations revealed an enhanced understanding of regulatory requirements in industry professionals through a combination of surveys, focus group discussions and tailored training workshops. These initiatives can equip the industry with knowledge to make informed decisions and enhance overall compliance with product defect reporting and recall procedures. The findings would be used to streamline our processes related to defect and recall.
Correction: Major Adverse Cardiovascular Events Related to JAK Inhibitors: A Disproportionality Analysis Using the WHO Global Individual Case Safety Database.
Di Napoli R, Richez C, Scavone C … +5 more , Singier A, Demourgues M, Mascolo A, Capuano A, Salvo F
Drug Saf · 2025 Aug · PMID 40261507 · Full text
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A Drug Similarity-Based Bayesian Method for Early Adverse Drug Event Detection.
Shi Y, Yang Y, Liu R … +5 more , Sun A, Peng X, Li L, Zhang P, Zhang P
Drug Saf · 2025 Aug · PMID 40261506 · Full text
INTRODUCTION: Biochemical drug similarity-based methods demonstrate successes in predicting adverse drug events (ADEs) in preclinical settings and enhancing signals of ADEs in real-world data mining. Despite these succes...
INTRODUCTION: Biochemical drug similarity-based methods demonstrate successes in predicting adverse drug events (ADEs) in preclinical settings and enhancing signals of ADEs in real-world data mining. Despite these successes, drug similarity-based ADE detection shall be expanded with false-positive control and evaluated under a time-to-detection setting. METHODS: We tested a drug similarity-based Bayesian method for early ADE detection with false-positive control. Under the tested method, prior distribution of ADE probability of a less frequent drug could be derived from frequent drugs with a high biochemical similarity, and posterior probability of null hypothesis could be used for signal detection and false-positive control. We evaluated the tested and reference methods by mining relatively newer drugs in real-world data (e.g., the US Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS) data) and conducting a simulation study. RESULTS: In FAERS analysis, the times to achieve a same probability of detection for drug-labeled ADEs following initial drug reporting were 5 years and ≥ 7 years for the tested method and reference methods, respectively. Additionally, the tested method compared with reference methods had higher AUC values (0.57-0.79 vs. 0.32-0.71), especially within 3 years following initial drug reporting. In a simulation study, the tested method demonstrated proper false-positive control, and had higher probabilities of detection (0.31-0.60 vs. 0.11-0.41) and AUC values (0.88-0.95 vs. 0.69-0.86) compared with reference methods. Additionally, we identified different types of drug similarities had a comparable performance in high-throughput ADE mining. CONCLUSION: The drug similarity-based Bayesian ADE detection method might be able to accelerate ADE detection while controlling the false-positive rate.
Signal Monitoring for Adverse Events Following Immunisation with COVID-19 Vaccines During the SARS-CoV-2 Pandemic: An Evaluation of the South African Surveillance System.
Sankar C, Evans S, Meyer JC … +3 more , Gunter HM, Sekiti V, McCarthy K
Drug Saf · 2025 Aug · PMID 40238055 · Full text
INTRODUCTION: Monitoring of adverse events following immunisation (AEFI) is recommended for post-licensure surveillance. We investigated whether the South African surveillance system could detect signals of disproportion...
INTRODUCTION: Monitoring of adverse events following immunisation (AEFI) is recommended for post-licensure surveillance. We investigated whether the South African surveillance system could detect signals of disproportionate reporting and whether these signals aligned with globally identified AEFI and adverse events of special interest (AESI) post-coronavirus disease-2019 (COVID-19) vaccination. METHODS: This retrospective pharmacovigilance study undertook disproportionality analysis of the National Department of Health AEFI database from the start of the COVID-19 vaccine rollout on 17 May 2021 to 31 December 2022. We complemented this with AEFI reports for vaccines not on the routine Expanded Programme on Immunisation schedule, to address potential masking of signals due to the high reporting rate of COVID-19 vaccine AEFI. RESULTS: During the study period, 3846 AEFI were reported for 37,537,009 doses of COVID-19 vaccines (BNT162b2 and Ad26.COV2.S) administered. The overall reporting rate was 10.2 per 100,000 doses, 18.1/100,000 and 7.9/100,000 for Ad26.COV2.S and BNT162b2, respectively. Comparison with other countries suggests underreporting. Disproportionate reporting signals were obtained for three and seven AEFI following BNT162b2 and Ad26.COV2.S vaccines, respectively. An additional three AEFI signals from Ad26.COV2.S emerged in the augmented dataset, indicating masking. All Ad26.COV2.S signals, and one BNT162b2 signal, appear in the vaccines' product information. Among nine AESI evaluated, myocarditis/pericarditis presented as a signal of disproportionate reporting following BNT162b2 vaccination. CONCLUSIONS: This study is one of the first from a lower-middle-income country, using a spontaneous reporting system for signal detection post-COVID-19 vaccination. Signals aligned with those reported globally. The study highlights the need to further investigate underreporting, masking, and system attributes for system strengthening.
Investigating Risk of Cancer with Sodium-Glucose Cotransporter 2 Inhibitors: A Disproportionality Analysis in the WHO Global Pharmacovigilance Database Vigibase.
Gautier P, Elbaz M, Bouisset F … +2 more , Despas F, Montastruc F
Drug Saf · 2025 Aug · PMID 40232585 · Full text
INTRODUCTION: Use of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) has significantly increased due to their cardiovascular benefits. Whether SGLT-2is increase risk of cancer has been of concern since first clinica...
INTRODUCTION: Use of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) has significantly increased due to their cardiovascular benefits. Whether SGLT-2is increase risk of cancer has been of concern since first clinical trials, but this question remains unclear because of methodological limitations in previous studies. METHODS: We conducted a disproportionality analysis using Vigibase between 2014 and 2023 to estimate the association between SGLT-2i use and the risk of reporting of different subtypes of cancers, compared with glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors. RESULTS: Among 644 reported cases of cancer associated with SGLT-2i use, 427 (66.3%) were male, with a mean age of 66.5 ± 9.7 years. Sodium-glucose cotransporter 2 inhibitors showed increased reporting odds ratio for bladder cancer (ROR 4.46, 95% CI 3.23-6.17) and kidney cancer (ROR 1.84, 95% CI 1.25-2.69), but not for all other cancer subtypes. CONCLUSION: In this disproportionality analysis with a hypothesis-generating approach, SGLT-2is are associated with an increased risk of reporting bladder and kidney cancer. There is a need of an urgent clarification of this signal with further long-term observational studies.
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