Drug Safety[JOURNAL]
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200 papers
Sexual Dysfunction in Male Patients After Initiating Treatment with Antidepressants.
Westphal L, Gräf DD, Le H … +2 more , Hallgreen CE, Andersen M
Drug Saf · 2026 Apr · PMID 41203969 · Full text
INTRODUCTION: Sexual side effects of serotonergic drugs are well documented. However, observational evidence comparing specific antidepressants remains sparse. OBJECTIVE: The aim of this study was to compare the risk of...
INTRODUCTION: Sexual side effects of serotonergic drugs are well documented. However, observational evidence comparing specific antidepressants remains sparse. OBJECTIVE: The aim of this study was to compare the risk of developing healthcare-recorded sexual dysfunction among male patients after initiating treatment with citalopram, sertraline, venlafaxine, or mirtazapine. METHODS: We conducted a new-user, active comparator cohort study of adult males in Denmark who started treatment with any of the study drugs between 2001 and 2015, allowing multiple cohort entries per person. Data from Danish national healthcare registers included 170,580 new treatment episodes of citalopram, 67,721 of mirtazapine, 51,984 of sertraline, and 19,820 of venlafaxine. A separate analysis examined patients with prior depression-related hospital visits. Results were reported as incidence rates as well as unmatched and propensity score-matched hazard ratios. RESULTS: In our primary analysis with 1-year follow-up and washout periods, incidence rates ranged from 18.80 (95% CI 17.60-20.00) to 28.5 (95% CI 26.00-31.30) per 1000 person-years. Venlafaxine was associated with the highest risk of healthcare-recorded sexual dysfunction compared with citalopram (hazard ratio [HR] 1.27; 95% CI 1.02-1.46), which was particularly pronounced among those with previous hospital contact for depression (HR 1.93; 95% CI 1.14-1.27). No significant difference was observed for sertraline (HR 0.99; 95% CI 0.90-1.09), while mirtazapine demonstrated modest evidence of a lower risk relative to citalopram (HR 0.87; 95% CI 0.81-0.93). Findings remained consistent across all analyses. CONCLUSIONS: The risk of developing sexual dysfunction varies across antidepressant treatment. Healthcare providers should discuss the potential for sexual side effects, particularly when multiple treatment options are available.
A National Response to Warfarin Shortages: Evaluating Regulatory Substitution and Notified Shortages and Their Effects on Antithrombotic Dispensings, Pathology Monitoring and Adverse Event Trends in Australia.
Azroun R, Ellett LK, Pratt N … +2 more , Ward M, Janetzki J
Drug Saf · 2026 Jun · PMID 41186801 · Publisher ↗
BACKGROUND: Medicine shortages are an increasing threat to medicine safety and access. In Australia, a 7-month shortage of Coumadin 5-mg tablets (Dec 2022-Jul 2023) prompted Therapeutic Goods Administration (TGA) interve...
BACKGROUND: Medicine shortages are an increasing threat to medicine safety and access. In Australia, a 7-month shortage of Coumadin 5-mg tablets (Dec 2022-Jul 2023) prompted Therapeutic Goods Administration (TGA) intervention via the Serious Scarcity Substitution Instrument (SSSI), allowing pharmacists to substitute 5-mg warfarin tablets with lower-strength tablets. Understanding the impact of this shortage on anticoagulant use and safety is essential for informing future regulatory responses. AIMS: The aim of this study was to assess the impact of the 2023 warfarin shortage in Australia on dispensing of warfarin and direct oral anticoagulants (DOACs), International Normalised Ratio (INR) testing, and adverse event reporting. METHODS: Monthly national dispensing data (January 2020-August 2024) were obtained from Pharmaceutical Benefits Scheme (PBS) Date of Supply data. INR pathology data were sourced from Services Australia. The TGA Medicines Shortages Database identified relevant shortage periods. Warfarin-related adverse events were extracted from the TGA Database of Adverse Event Notifications. Interrupted time series assessed changes in dispensing and INR testing trends over time. RESULTS: Warfarin dispensing declined by 1094 prescriptions per month prior to March 2023 (p < 0.0001). A short-term increase occurred in March 2023 (+ 8625 prescriptions; p = 0.0017) following implementation of the SSSI, although this was not sustained. At the warfarin strength level, dispensing rose for warfarin 1 mg and 2 mg but fell for 5 mg, with subsequent compensatory increases; 3 mg remained stable. DOAC dispensing increased steadily before March 2023 (+ 3771 prescriptions per month; p < 0.0001) but declined thereafter (- 3056 per month; p < 0.0001), most notably for rivaroxaban and dabigatran, while apixaban decreased non-significantly. INR testing briefly increased during the shortage and SSSI. A modest rise in haemorrhage-related adverse events was observed. CONCLUSION: Warfarin supply was maintained during the 2023 shortage through strength-based substitution under the SSSI, with limited impact on DOAC dispensing.
Sexual Dysfunctions Associated with Proton Pump Inhibitors: Insights from VigiBase, the World Health Organization Pharmacovigilance Database.
Crisafulli S, Ciccimarra F, Scapini F … +7 more , L'Abbate L, Jannini EA, De Martino MC, Giannetta E, Mestres J, Tuccori M, Trifirò G
Drug Saf · 2026 Apr · PMID 41171556 · Full text
BACKGROUND: Over the years, several observational studies and case reports have been published hypothesizing a potential association between the use of proton pump inhibitors (PPIs) and sexual dysfunctions in both male a...
BACKGROUND: Over the years, several observational studies and case reports have been published hypothesizing a potential association between the use of proton pump inhibitors (PPIs) and sexual dysfunctions in both male and female patients. OBJECTIVES: We aimed to investigate the potential association between PPI use and sexual dysfunction onset using VigiBase, the World Health Organization international pharmacovigilance database. METHODS: All individual case safety reports of sexual dysfunctions containing PPIs (i.e. omeprazole, lansoprazole, rabeprazole, pantoprazole and esomeprazole) as suspected or interacting drugs until 4 September, 2024 were selected from VigiBase using the Standardised MedDRA Query "Sexual dysfunction". A descriptive analysis of the selected individual case safety reports was carried out. Potentially new safety signals were identified through a disproportionality analysis and calculated as a reporting odds ratio (ROR) along with a 95% confidence interval (CI), which were adjusted via Bonferroni correction for multiple testing. To account for age-related effects on sexual functions, a subgroup analysis was carried out by restricting the study population only to patients aged from 18 to 64 years. RESULTS: A total of 420,598 individual case safety reports concerning PPIs were collected in VigiBase during the study period. Of these, 841 containing at least one Preferred Term included in the "Sexual dysfunction" Standardised MedDRA Query reporting information on sex were retrieved. Overall, disproportionate reporting for omeprazole concerning erectile dysfunction (adjusted ROR, 1.76; 95% CI 1.54-2.01) was observed, while two statistically significant adjusted RORs for esomeprazole, i.e. genital discomfort (ROR, 3.66; 95% CI 1.34-10.04) and oestrogen deficiency (ROR, 3.80; 95% CI 1.03-13.99) in female patients were found. The subgroup analysis confirmed the statistically significant disproportionate reporting of erectile dysfunction for omeprazole (adjusted ROR: 1.80; 95% CI 1.49-2.16), and generated new potential safety signals including an omeprazole-induced libido decrease (adjusted ROR, 1.49; 95% CI 1.05-2.12) and esomeprazole-induced hypogonadism (adjusted ROR, 5.22; 95% CI 1.22-22.34) in male individuals, and omeprazole-induced genital discomfort (adjusted ROR, 3.55; 95% CI 1.13-11.09) in female individuals. CONCLUSIONS: Findings of this study suggest the presence of safety signals of PPI-induced sexual dysfunctions, such as erectile dysfunction, genital discomfort and oestrogen deficiency. However, further observational studies are required to validate and further characterise these potential safety signals.
Strengthening Signal Detection in Pharmacovigilance by Using International Nonproprietary Name (INN) Stems.
Balocco R, Aronson JK, Malan SF … +1 more , Figueras A
Drug Saf · 2026 Apr · PMID 41138033 · Full text
'Stems', which mark pharmacological relationships between substances, form the backbone of the International Nonproprietary Name (INN) system, developed by the WHO in the 1950s. In this paper, we propose using the INN st...
'Stems', which mark pharmacological relationships between substances, form the backbone of the International Nonproprietary Name (INN) system, developed by the WHO in the 1950s. In this paper, we propose using the INN stems to enhance pharmacovigilance signal detection. After analysis of historical cases and current pharmacovigilance practices, we discuss how stem-based classification could facilitate understanding of the adverse-effects profile of each stem, to be used as a benchmark for early identification of adverse drug reactions that deviate from expected class effects, in other words signals associated with newly marketed medicines or different uses of well-known medicines. We propose a potential framework for integrating stem-based analysis into existing pharmacovigilance databases, supplemented by artificial intelligence approaches, such as machine learning. While acknowledging limitations, such as stem variability and reporting bias, we suggest that this approach offers potential advantages for regulatory authorities and healthcare professionals in post-marketing surveillance. Implementation of stem-based post-marketing surveillance could enhance signal-detection efficiency and contribute to improved patient safety through earlier identification of unexpected adverse effects and adverse reactions.
Incretin-Based Drugs and the Risk of Dementia Among Patients with Type 2 Diabetes.
Wang YH, Johnson K, Beradid S … +5 more , Yin H, Yu OHY, Suissa S, Azoulay L, Renoux C
Drug Saf · 2026 Apr · PMID 41123870 · Publisher ↗
BACKGROUND: Incretin-based drugs, namely glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, may have neuroprotective effects. Thus, we assessed whether these drugs are as...
BACKGROUND: Incretin-based drugs, namely glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, may have neuroprotective effects. Thus, we assessed whether these drugs are associated with a decreased risk of dementia among patients with type 2 diabetes. METHODS: Using the Clinical Practice Research Datalink from the UK, we formed two new user cohorts of patients at least 50 years of age with type 2 diabetes starting incretin-based drugs or sulfonylureas between 2007 and 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia were estimated separately for GLP-1 RAs and DPP-4 inhibitors using Cox proportional hazards models with propensity score fine-stratification weighting and inverse probability of censoring weights. RESULTS: Among 275,144 initiators of DPP-4 inhibitors or sulfonylureas, followed for 750,846 person-years, DPP-4 inhibitors were associated with a reduced dementia risk compared with sulfonylureas (4.4 vs. 5.7 events per 1000 person-years; HR 0.77, 95% CI 0.71-0.85). HRs decreased with increasing cumulative duration of use and dose. Similar associations were observed across dementia subtypes and individual DPP-4 inhibitors molecules. Among 181,215 initiators of GLP-1 RAs or sulfonylureas, followed for 530,415 person-years, GLP-1 RAs were associated with a similar reduction in dementia risk compared with sulfonylureas, although with high uncertainty (2.3 vs. 3.1 events per 1000 person-years; HR 0.74, 95% CI 0.46-1.18). The magnitude of the association increased with cumulative duration of use and dose but with high uncertainty. CONCLUSIONS: In this population-based study, DPP-4 inhibitors, and possibly GLP-1 RAs, were associated with a reduced dementia risk compared with sulfonylureas.
Anticholinergic Drug Use in Elderly Patients: Compliance with STOPP-START and BEERS Criteria in Spain-A Descriptive Study.
Santandreu J, Caballero FF, González-Burgos E
Drug Saf · 2026 Feb · PMID 41107681 · Publisher ↗
INTRODUCTION: Dementia is the most prevalent neurodegenerative disorder. Several studies have demonstrated an association between anticholinergic drug use and an increased risk of cognitive and physical impairment. Howev...
INTRODUCTION: Dementia is the most prevalent neurodegenerative disorder. Several studies have demonstrated an association between anticholinergic drug use and an increased risk of cognitive and physical impairment. However, anticholinergic drugs are commonly prescribed for various clinical conditions, and their cumulative effects, referred to as anticholinergic burden, can contribute to cognitive decline and dementia. Although the causal relationship remains inconclusive, a higher anticholinergic burden is linked to a greater risk of cognitive deterioration. OBJECTIVE: This study aims to assess the compliance of patients aged ≥ 65 years with the STOPP-START and Beers criteria concerning the concurrent use of medications with high anticholinergic potency in situations where their use is not clinically justified. METHODS: This observational descriptive study was conducted using data from the Spanish Database for Pharmacoepidemiological Research (BIFAP). The study population comprised male and female patients aged ≥ 65 years. RESULTS: Of the 81,405 patients who developed dementia during the study period, 46.7% had been exposed to multiple anticholinergic drugs. Among them, 81.1% used these drugs sequentially, while 18.9% used two or more simultaneously. The absolute risk of developing dementia was 6.5% in patients who met the STOPP-START and BEERS criteria, compared to 13.4% in those who did not. CONCLUSION: Although a high anticholinergic burden is a risk factor for cognitive decline, the unjustified concurrent use of multiple anticholinergic drugs remains uncommon among the elderly population in Spain.
Navigating Non-interventional Post-authorization Studies in East Asia: Regulatory Challenges, Opportunities, and Future Directions.
Peters J, Ali AK, Moitinho de Almeida M … +8 more , Asao K, Hammad TA, He X, Michel A, Rubino A, Sawada S, Sobel RE, de Vogel S
Drug Saf · 2026 Mar · PMID 41105321 · Full text
Post-authorization studies (PAS) are often mandated by regulatory authorities as a condition of marketing authorization of pharmaceutical products. This article explores specific regulations and trends in China, Japan, a...
Post-authorization studies (PAS) are often mandated by regulatory authorities as a condition of marketing authorization of pharmaceutical products. This article explores specific regulations and trends in China, Japan, and South Korea, highlighting the scientific and operational limitations that such PAS pose to the stakeholders in these regions including significant variations in regulatory requirements. Pharmacovigilance guidelines and publications on regional regulatory trends were reviewed. Active surveillance studies are widely adopted to fulfill post-authorization requirements in East Asia countries. These are primary data collection studies, i.e., traditional site-based studies that monitor the frequency of all adverse events (and clinical outcomes when requested) of the newly approved pharmaceutical product during a predefined treatment period. Such studies generally present limitations regarding the product's safety profile characterization, including the absence of a comparator group, selection bias, limited sample size, and considerable resources needed to conduct the studies. These limitations explain the trend toward hypothesis testing studies, conducted with secondary data (e.g., large electronic database studies) as preferred over traditional active surveillance studies. Harmonizing regulatory approaches and enhancing access to comprehensive data sources are critical for generating fit-for-purpose evidence to support regulatory decision making in these regions. Therefore, we propose a decision tool to assist with the planning of PAS in China, Japan, and South Korea. This article is endorsed by the International Society for Pharmacoepidemiology (ISPE).
24th ISoP Annual Meeting "Pharmacovigilance: Back to the Future" 24-27 October 2025 Cairo, Egypt.
Drug Saf · 2025 Dec · PMID 41099921 · Publisher ↗
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Correction: Charting and Sidestepping the Pitfalls of Disproportionality Analysis.
Fusaroli M, Sartori D, van Puijenbroek EP … +1 more , Norén GN
Drug Saf · 2025 Dec · PMID 41091354 · Full text
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Systematic Review Examining the Effectiveness of Professional, Organisational and Structural Interventions in Primary Care to Reduce Medication-Related Hospitalisations and Deaths.
Khalil H, Bell BG, Keers RN … +7 more , Lewis PJ, Foreman M, Taylor A, Iyen B, Sheikh A, Ashcroft DM, Avery AJ
Drug Saf · 2026 Apr · PMID 41087738 · Full text
BACKGROUND: Medication-related adverse events in primary care are a leading cause of hospital admissions and mortality, commonly resulting from medication errors. Previous reviews have assessed interventions broadly acro...
BACKGROUND: Medication-related adverse events in primary care are a leading cause of hospital admissions and mortality, commonly resulting from medication errors. Previous reviews have assessed interventions broadly across healthcare settings, but few have focused specifically on interventions targeting medication errors in primary care. OBJECTIVE: To evaluate the effectiveness of professional, organisational, and structural interventions in primary care settings in reducing medication-related hospital admissions, emergency department (ED) visits, and mortality. METHODS: We conducted a systematic review using the Cochrane methodology of systematic reviews and PRISMA guidelines for reporting. A comprehensive search of CENTRAL, MEDLINE, Embase, CINAHL, and trial registries up to October 2024 was undertaken. Randomised controlled trials conducted in primary care that assessed the impact of interventions on hospital admissions, ED visits, and mortality were included. Cochrane Risk of bias assessments and random-effects meta-analyses were performed. RESULTS: Interventions were classified according to the Cochrane Effective Practice and Organisation of Care criteria into Professional, Organisational and Structural. Sixty-two studies met the inclusion criteria. Professional interventions, including educational training and clinical decision tools, showed little to no effect on primary outcomes (risk ratio [RR] 1.01, 95% confidence interval [CI] 0.94-7.00 for hospital admissions; RR 1.00, 95% CI 0.98-1.02 for mortality; very-low to low certainty evidence). Organisational interventions, such as pharmacist-led medication reviews and multidisciplinary care models reduced the number of hospital admissions (RR 0.81, 95% CI 0.70-0.95; low-certainty evidence), but had uncertain effects on ED visits and mortality. Structural interventions, such as system-level support and quality monitoring, showed a reduction in hospital admissions (RR 0.90, 95% CI 0.83-0.97; moderate-certainty evidence), but evidence for other outcomes showed limited or very-low certainty. CONCLUSION: Organisational and structural interventions in primary care may reduce medication-related hospital admissions and may help inform clinical practice through implementation of multidisciplinary care models and system-level quality monitoring approaches. However, the overall certainty of evidence is low to very low, highlighting the need for high-quality trials to better inform clinical practice and policy.
Harm to Children from Prescribing and Administration Errors in Acute Care: A Multidisciplinary Panel Assessment.
Mumford V, Raban MR, Fitzpatrick E … +13 more , Woods A, Merchant A, Badgery-Parker T, Li L, Gates P, Day RO, Ambler G, Dalla-Pozza L, Gazarian M, Gardo A, Barclay P, White L, Westbrook JI
Drug Saf · 2026 Mar · PMID 41053408 · Full text
INTRODUCTION: Medication errors continue to cause inpatient harm in children and can be difficult to both identify and classify. Medication error studies often focus on assessing potential harm and there is little publis...
INTRODUCTION: Medication errors continue to cause inpatient harm in children and can be difficult to both identify and classify. Medication error studies often focus on assessing potential harm and there is little published data on actual harm from medication errors in children. OBJECTIVE: Our aim was to use multidisciplinary panels to identify and describe the actual harm resulting from prescribing and administration medication errors occurring at a major paediatric hospital. METHODS: We reviewed medication error data collected from retrospective medication record reviews to identify prescribing errors (26,369 orders, 19,692 errors and 3782 patients) and prospective direct observations (5137 dose administrations, 3663 errors and 1530 patients) to identify administration errors. Errors with the potential to cause serious harm and with evidence that the error reached the patient formed the dataset for our study. Case studies (n = 566) describing the prescribing and administration errors and a brief clinical summary were reviewed by multidisciplinary panels to determine whether there was evidence in patients' records of actual harm and to rate the severity of the harm identified. RESULTS: Actual harm was identified in 89 case studies and rated as minor in 43% (n = 38), moderate in 48% (n = 43) and serious in 9% (n = 8). There were no cases of harm rated as severe resulting in death. Antibacterials were the most common medications in cases with harm (n = 38/89 cases), and dosing errors (n = 32/89) the most common error type associated with harm. Younger patients had a significantly (t = 2.4, df = 198, p = 0.017) greater risk of actual harm from medication errors, and children aged under 12 months formed a higher proportion of those with actual harm (χ (1, N = 566) = 10.5, p = 0.001). The most frequent type of administration errors leading to harm were wrong infusion rates of intravenous antibiotics (19/67 cases); 12 of these instances occurred in children under 12 months. Administration errors were more likely to result in actual harm (1.83%; 67 /3663 errors) compared with prescribing errors (0.21%; 42/19,692). CONCLUSIONS: We found higher rates of actual harm associated with medication errors in younger patients, wrong dose prescribing errors and intravenous antibiotic administration errors. These important findings provide opportunities for developing tailored interventions targeting identified high-risk areas to enable the successful reduction of preventable harms in paediatric patients.
Statistical Methods for Multi-jurisdictional Australian Vaccine Safety Investigations of Rare Adverse Events.
Morgan HJ, Bloomfield L, Clothier HJ … +7 more , Ngeh S, Cadby G, Carcione D, Boyd JH, Kattan GS, Buttery JP, Effler P
Drug Saf · 2026 Mar · PMID 41032228 · Full text
BACKGROUND: In Australia, surveillance of adverse events following immunisation is primarily conducted by states and territories, with each jurisdiction only able to view and analyse reports originating from their own po...
BACKGROUND: In Australia, surveillance of adverse events following immunisation is primarily conducted by states and territories, with each jurisdiction only able to view and analyse reports originating from their own population. Distributed data models (aka federated data models) are a form of decentralised collaboration, with each site maintaining ownership of its data from end-to-end including data collection, storage and analysis. The primary benefit of this model is that it maintains independence and autonomy while enabling interdependence, collaboration and scalability. OBJECTIVE: We aimed to investigate statistical methods for a multi-jurisdictional collaboration when conducting a rigorous assessment of rare adverse events following immunisation at a national level. METHODS: Victoria and Western Australia have independently established routine data linkage for vaccine safety surveillance. A data collaboration model is proposed, whereby each jurisdiction can generate de-identified population-level data for adverse events following immunisation, using agreed case definitions and analytical methods. To demonstrate its utility, Victoria and Western Australia combined data from a self-controlled case series via a meta-analysis approach using aggregate data and a pooled approach using individual-level data to investigate the association between coronavirus disease 2019 vaccines and Guillain-Barré syndrome. RESULTS: There were 519 and 176 new Guillain-Barré syndrome International Classification of Diseases, Tenth Revision, Australian Modification coded admissions in Victoria and Western Australia, respectively, between 01/01/2020 and 31/12/2023. Combining data using a fixed-effect meta-analysis method (relative incidence: 2.64, 95% confidence interval 1.90, 3.66) and a pooled method (relative incidence: 2.45, 95% confidence interval 1.76, 3.41) confirmed the known increased incidence in the 42 days following a coronavirus disease 2019 Vaxzevria vaccination. Both methods resulted in a decreased standard error when compared with either state alone. CONCLUSIONS: This project represents an ongoing successful collaboration between two Australian jurisdictions using data linkage to investigate rare adverse events following immunisation and inform accurate benefit-risk analyses. The decision to use meta-analysis and pooled analysis methods should be considered on a case-by-case basis and may depend on data-sharing agreements, the ease of pooling potentially discordant data variables and underlying population characteristics.
Choosing an Index Date for Untreated Patients in External Comparator Studies.
Antunes L, Rippin G, Ralphs E … +3 more , Luguzis A, Arnold K, Lee H
Drug Saf · 2026 Mar · PMID 41021206 · Publisher ↗
BACKGROUND AND OBJECTIVE: Selecting an index date (also called time zero or baseline) can be challenging for External Comparator (EC) studies when comparing against untreated patients. Existing literature addresses metho...
BACKGROUND AND OBJECTIVE: Selecting an index date (also called time zero or baseline) can be challenging for External Comparator (EC) studies when comparing against untreated patients. Existing literature addresses methods for defining an index date for untreated patients in observational studies generally, but not for EC studies specifically, which are likely to benefit from customized approaches. METHODS: A simulation study was performed to assess different index date assignments and analytical approaches in terms of bias and other performance characteristics: The first approach took the time from a major clinical event (say, diagnosis date) to treatment start as observed in the treated cohort and randomly assigned these times to the untreated cohort to derive the index dates. This approach was applied without and with the condition that the emulated index dates in the untreated cohort needed to be before the observed event times (index date emulation [IDE] and modified index date emulation approach [mIDE]). The second approach was to start the follow-up period at the diagnosis date (early index date approach [EID]) and to perform an analysis according to a time-dependent Cox model (or its generalization, e.g., a Marginal Structural Cox Model). This model was applied both in a traditional but also in a modified manner (modified early index date approach, mEID), where the modified model coded the treatment cohorts before the true (treated patients) and emulated (untreated patients, using IDE) treatment start dates to belong to a third treatment category. This allowed the treatment comparison of interest to be restricted to the time after the true and emulated treatment start dates. RESULTS: The IDE and mEID approaches were shown to be unbiased with identical performance, while mIDE and EID exhibited significant bias. CONCLUSIONS: We showed that our EC analysis approach based on emulated index dates for untreated patients constitutes a valid concept, which may be advantageous for many external comparator studies.
Comment on: Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study.
Weng CH, Chan PA, Magagnoli J … +1 more , Bennett CL
Drug Saf · 2026 Feb · PMID 41003919 · Publisher ↗
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Authors' Response to Weng et al.'s Comment on "Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study".
Mansi IA, Boktor M
Drug Saf · 2026 Feb · PMID 41003918 · Publisher ↗
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Content Analysis of Promotional Materials for Prescription Drugs Authorized Under Emergency Use Authorization.
Kelly B, Aikin KJ, Sullivan HW … +7 more , Madson G, Jeffroy-Menard AC, Hawkins D, Vu K, Liu S, McCormack L, Quinn SC
Drug Saf · 2026 Mar · PMID 40999286 · Publisher ↗
INTRODUCTION: Under Section 564 of the Federal Food, Drug and Cosmetic Act, the United States (US) Food and Drug Administration (FDA) may, pursuant to a declaration by the US Department of Health and Human Services Secre...
INTRODUCTION: Under Section 564 of the Federal Food, Drug and Cosmetic Act, the United States (US) Food and Drug Administration (FDA) may, pursuant to a declaration by the US Department of Health and Human Services Secretary, based on one of four types of determinations, authorize an unapproved product or unapproved uses of an approved product for emergency use. Although sponsors are not prohibited from promoting products with Emergency Use Authorizations (EUAs), little is known about how they promote these products. OBJECTIVES: The aim of this study was to investigate how EUAs are being described in promotional materials disseminated to health care providers (HCPs) and consumer audiences. METHODS: A content analysis was conducted on promotional materials for drugs authorized under an EUA that were submitted to the FDA between April 2020 and April 2023. Each material was coded for the presence or absence and location of certain words, phrases, or resources relating to EUAs and product risk information. Statistical analyses include descriptive statistics and bivariate analyses comparing materials created for consumer and HCP audiences. Readability statistics were also conducted for consumer materials. RESULTS: The sample included 423 promotional materials. Most materials included risk information; however, few included a formal definition of an EUA. Materials for HCPs were more likely to contain links to fact sheets and other information and resources related to EUAs. The reading level of consumer materials was very difficult (requiring graduate-level education). CONCLUSION: Although most of the materials contained risk and benefit information in promotional materials about EUAs, improvements could be made through the inclusion of a specific definition of "EUA" and more prominent information about limitations of use in consumer materials. Readability could also be improved for consumer materials by applying plain language principles.
Charting and Sidestepping the Pitfalls of Disproportionality Analysis.
Fusaroli M, Sartori D, van Puijenbroek EP … +1 more , Norén GN
Drug Saf · 2026 Feb · PMID 40993470 · Full text
Disproportionality analysis is used by many pharmacovigilance organizations for detecting and assessing signals of potential adverse drug reactions. However, its goal is often misunderstood and the approach misapplied, l...
Disproportionality analysis is used by many pharmacovigilance organizations for detecting and assessing signals of potential adverse drug reactions. However, its goal is often misunderstood and the approach misapplied, leading to erroneous conclusions due to neglected violated assumptions. In this paper we illustrate how simplistic use and interpretation of disproportionality analysis can lead to incorrect conclusions. Using VigiBase, the WHO global database of adverse event reports, and the Information Component disproportionality metric, we provide selected examples to highlight common sources of error that can introduce spurious disproportionalities or lead to missing important signals: confounding (by age, sex, indication, comedication), effect modification (by age), notoriety bias, masking, misclassification (by miscoding, incomplete or imprecise event retrieval), neglecting report utility, and violated independence assumption. Additionally, we present how sophisticated analyses may introduce new biases or amplify existing ones, such as collider bias or masking amplification. Due to its pitfalls, disproportionality analysis plays a supportive rather than decisive role in signal detection and assessment. Careful design and interpretation of disproportionality analysis, with appropriate subgrouping and clinical assessment, are essential. While subgrouping can mitigate some pitfalls, it reduces sample size and may introduce or amplify existing biases and needs to be used with care. Further development of tools to detect and mitigate biases in disproportionality analyses, and to assess their risk of bias, is needed.
Managing Drug Interactions with Enzalutamide in Patients with Prostate Cancer: A Podcast.
Morgans AK, Looney B, Mack J … +1 more , Bianco J
Drug Saf · 2026 Jan · PMID 40956486 · Full text
Enzalutamide is an oral androgen receptor signaling inhibitor used in the treatment of prostate cancer. Elderly patients with prostate cancer commonly have age-related comorbidities that require concomitant, active treat...
Enzalutamide is an oral androgen receptor signaling inhibitor used in the treatment of prostate cancer. Elderly patients with prostate cancer commonly have age-related comorbidities that require concomitant, active treatment. As a moderate inducer of the cytochrome P450 (CYP) enzymes CYP2C9 and CYP2C19, and a strong inducer of CYP3A4, there is potential for drug-drug interactions (DDIs) when enzalutamide is coadministered with other drugs that are CYP3A4 substrates-resulting in loss of efficacy or increased risk of unintended drug-related adverse events. In this podcast, we describe enzalutamide including its dosing, pharmacokinetics, and potential for interaction with coadministered drugs using several hypothetical patient cases with real-world clinical implications. Discussion of each patient case will highlight management strategies and illustrate that nearly all enzalutamide drug-drug interactions can be effectively managed with appropriate knowledge of which drugs pose interaction risks, when dose adjustments are indicated, and when alternative drugs can be substituted. Supplementary file1 (MP4 192541 KB).
Characterizing the FDA Adverse Event Reporting System (FAERS) as a Network to Improve Pattern Discovery.
Davis R, Dang O, De S … +1 more , Ball R
Drug Saf · 2026 Feb · PMID 40956485 · Publisher ↗
INTRODUCTION: In drug-safety monitoring systems, adverse events (AEs) associated with the use of medical products often consist of complex patterns of clinical events. Network analysis (NA) was used for pattern recogniti...
INTRODUCTION: In drug-safety monitoring systems, adverse events (AEs) associated with the use of medical products often consist of complex patterns of clinical events. Network analysis (NA) was used for pattern recognition and characterizing the Vaccine Adverse Event Reporting System (VAERS), but limited applications of NA to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) left its network description incomplete. METHODS: In this analysis, the network properties of FAERS were characterized and leveraged to facilitate pattern discovery. Reported AE information in FAERS is represented using preferred terms (PTs) in Medical Dictionary for Regulatory Activities terminology. The FAERS subsets were analyzed with drugs and PTs as nodes and interconnections as edges. Global characteristics, like the scale-free nature of the distribution, were examined to explore theoretical and structural considerations. Metrics that assess connectivity and edge weighting algorithms based on report co-occurrence or clustering were applied. RESULTS: Serious AE reports from 2016 to 2023 (2,062,099) were represented as a network of 20,965 nodes (16,847 PTs and 4116 drugs) with more than four million interconnections. Characteristics of FAERS subnetworks were determined with heavy-tailed degree distributions, high local clustering, and low diameters. Complexities related to structural and evolutionary characteristics were revealed as the log-normal model fits the degree distribution better than the power law. CONCLUSIONS: Network-based techniques identified clinically relevant patterns and clustering patterns representative of known adverse drug reactions. Comparisons to VAERS reveal similarities in networks of AE reporting systems. This initial systematic application of NA to FAERS describes the overall network characteristics of the FAERS database and provides insight into the use of network applications in drug safety research.
Implied ADR-Admissions: A Cohort Study Introducing a Novel Administrative Data Approach for Identifying Drug-Related Hospitalisations.
Schechner M, Rottenkolber M, Weglage C … +6 more , Brišnik V, Haerdtlein A, Guthrie B, Jaehde U, Grill E, Dreischulte T
Drug Saf · 2026 Mar · PMID 40956484 · Full text
BACKGROUND: Adverse drug reactions (ADRs) are a key contributor to unplanned hospitalisations, particularly in patients with polypharmacy. Traditional detection methods, such as expert reviews or diagnostic coding, are l...
BACKGROUND: Adverse drug reactions (ADRs) are a key contributor to unplanned hospitalisations, particularly in patients with polypharmacy. Traditional detection methods, such as expert reviews or diagnostic coding, are limited in scalability and sensitivity. OBJECTIVE: This study introduces and evaluates a novel scalable method, implied ADR-admissions, that links drug exposures to adverse events using administrative data to improve the detection of plausible drug-related hospitalisations. METHODS: A retrospective cohort study was conducted using linked health data from 123,662 individuals aged ≥ 40 years with polypharmacy in two Scottish health boards. Implied ADR-admissions were defined as emergency hospitalisations with one of 15 adverse events plausibly linked to drug exposure (based on a structured consensus process) within the prior 90 days. Incidence was compared with three existing approaches: adverse event-admissions (regardless of drug exposure), explicit ADR-admissions (explicitly coded as ADRs) and preventable ADR-admissions (with prior medication error). Multivariate logistic regression was used to identify predictors of implied ADR-admissions. RESULTS: Over 1 year, 2.6% experienced an implied ADR-admission, compared with 5.7% with adverse event-admissions, and 0.4% with explicit ADR-admissions. For gastrointestinal bleeding, the implied ADR-admission incidence was 20 times higher than the preventable ADR-admission incidence. Key predictors for implied ADR-admissions included prior hypokalaemia-related hospitalisation and use of potentially inappropriate medications. CONCLUSIONS: The implied ADR-admission approach has improved specificity relative to broad adverse event definitions while enhancing sensitivity beyond methods that rely solely on explicit ADR codes or pre-specified medication errors. It offers a scalable automated tool for pharmacovigilance, though further validation is needed prior to routine use in medication safety monitoring.
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