Pharmacoepidemiology and Drug Safety最新文献

Background: Assessing medication safety in the pediatric population can take many forms, but given the shortcomings of traditional methods, there has been a shift toward leveraging real-world data to bolster these efforts.

Objectives: To characterize demographics, enrollment, and health characteristics among pediatric members in the Sentinel Distributed Database (SDD).

Methods: Using administrative healthcare data from the SDD between January 1, 2000, and May 8, 2023, we used descriptive statistics to characterize the demographics, enrollment, and select health characteristics of pediatric members in the following age groups: 29 days-< 24 months (infants), 2-< 6 years (young children), 6 -< 12 years (older children), 12-< 18 years (early adolescents), and 18-21 years (late adolescents).

Results: Older children (6-< 12 years of age) represented the largest pediatric age group in the SDD, with over 46 million members, though there were between 27.5 and 45.4 million members in each of the other age groups as well. Estimates of common health conditions and medication use were in line with current national estimates.

Conclusions: The FDA's Sentinel Distributed Database accurately captures key aspects of pediatric health and can be used as an adjunct to current methods to assess and monitor the safety of approved medical products in the pediatric United States population.

Purpose: Anticoagulation therapy is required to prevent thromboembolic complications in patients with heart valve surgery (HVS). However, caution must be taken due to the risk of bleeding. This study aimed to identify bleeding risk factors in patients with stable warfarin therapy and develop a predictive tool for high-risk patients.

Methods: This study is a nested case-control design using the Korean National Health Insurance Service-National Sample Cohort Data. We identified patients who underwent HVS and were prescribed warfarin within 1 week after the procedure. Of these, patients with the last two identical warfarin prescriptions within 6 months before the bleeding events were defined as the case group, while patients with no bleeding events within 6 months after HVS and two consecutive identical warfarin prescriptions were defined as the control group. Three machine learning models-logistic regression, support vector machine, and random forest-were trained and scored by fivefold validation to validate our feature selection processes. We developed a risk scoring system using adjusted odds ratios from multivariate logistic regression.

Results: Of 1 137 861 subjects, 1093 patients were eligible for the study cohort; 173 and 298 were selected as the case and control groups, respectively. After a series of machine learning processes, eight features were identified as significant risk factors for bleeding events.

Conclusion: Our finding suggests that furosemide, spironolactone, lacrimal system disorders, ursodeoxycholic acid, captopril, chronic kidney disease, zolpidem, and valsartan are the most important features for predicting bleeding events in patients taking a stable warfarin dose after HVS.

Purpose: The potential of vancomycin to cause acute kidney injury (AKI) in adult intensive care patients is subject to debate due to suboptimal designs of past studies. Therefore, we aimed to estimate the effect of initiating vancomycin versus one of several minimally nephrotoxic alternative antibiotics on the 14-day risk of AKI using the target trial emulation framework.

Methods: A hypothetical trial was emulated using routinely collected data from 15 Dutch intensive care units (ICUs) spanning 2010-2019. We used an active comparator control group with the following alternative antibiotics: clindamycin, linezolid, teicoplanin, meropenem, cefazolin, and daptomycin. AKI was diagnosed according to the KDIGO serum creatinine (SCr) criteria. Cumulative incidence curves were estimated using the Aalen-Johansen method and adjusted for confounding and selection bias through inverse probability of treatment and censoring weighting. Given the time lag of 24-48 h between changes in renal function and SCr, we summarized the estimates by calculating the absolute risks and risk differences at both 2 and 14 days after initiation.

Results: We included 1809 ICU admissions. After adjustment, vancomycin was associated with a higher risk of AKI at 14 days of follow-up compared to the alternative antibiotics (0.28 [95% confidence interval (CI) 0.21-0.34] vs. 0.17 [95% CI 0.14-0.20]; risk difference 0.11 [95% CI 0.04-0.19]), but not at 2 days of follow-up (0.10 [95% CI 0.06-0.12] vs. 0.10 [95% CI 0.08-0.11]; risk difference 0.00 [95% CI -0.03-0.03]).

Conclusions: Our findings indicate that vancomycin causes a higher risk of AKI compared to the alternative antibiotics. We recommend clinicians to be compliant with vancomycin-induced AKI prevention strategies, such as therapeutic drug monitoring or the consideration of an alternative antibiotic if possible.

Background: The quality of real-world data (RWD) directly impacts the value of real-world evidence (RWE) generated for regulatory decision-making. Data owners and investigators must be prepared to provide documentation on data quality assessments to regulators when submitting secondary data for regulatory purposes. While robust feasibility is required to justify the relevance of a data source for a specific research question, the reliability of the data, including the chain of custody and data journey prior to reaching the end user, is of equal importance for drawing valid, meaningful conclusions.

Aims: Recently, Castellanos et al. constructed a definition of RWD quality by synthesizing definitions across published guidelines to characterize quality attributes of Flatiron Health RWD. In this paper, the transparent reporting of how data quality attributes (as defined by Castellanos et al.) are met in a single RWD source is replicated for the Guardian Research Network (GRN), a database of aggregated electronic health records (EHRs) collected from a geographically representative consortium of regional community health systems with experienced cancer research programs.

Materials & methods: We first describe GRN, including the data elements collected, timeliness of data availability, representativeness, and data access considerations. We then provide descriptions of how data reliability (accuracy, traceability, timeliness, completeness) and relevance (availability, sufficiency, representativeness) are ensured and assessed in GRN, including illustrative examples of relevant data quality checks.

Results: Descriptions of GRN's data quality processes demonstrate structured approaches to ensuring both reliability and relevance, aligned with published guidelines. Illustrative examples highlight the application of specific quality checks and their outcomes for GRN data.

Discussion: These findings illustrate the importance of documenting and communicating data quality attributes for RWD sources intended for regulatory use. Structured, transparent reporting can support more informed feasibility assessments and facilitate regulator confidence in RWE generation.

Conclusion: Continued development of structured approaches to identifying data fit for regulatory use underscores the need for comprehensive information about putative data sources during feasibility to inform decision making, study design, and elicit transparent conversations with regulators.

Introduction: Pharmacovigilance plays a critical role in ensuring the safety of medicinal products, particularly those under additional monitoring (AM). The European Union (EU) implemented AM in 2012 to enhance post-marketing surveillance. However, its impact on adverse drug reaction (ADR) reporting and pharmacists' role remains insufficiently explored. This scoping review examines the influence of AM label on ADR reporting management, and pharmacists' awareness and involvement in AM medicines.

Methods: A systematic search across four scientific databases (Web of Science, Scopus, Science Direct, and PubMed) and gray literature sources, covering studies published between 2012 and 2024 in the EU, identified 17 relevant studies according to eligibility criteria: AM labeling's impact on pharmacovigilance in the EU. Relevant data (title, year of publication, country, field, design, objective, results) and relation with research questions were charted.

Results: AM label alone does not significantly increase ADR reporting rates. However, structured training programs and targeted interventions for healthcare professionals (HCPs), particularly pharmacists, lead to improved ADR reporting and patient safety outcomes. Pharmacists exhibit the highest awareness of AM among HCPs but often underutilize their role in ADR reporting. Different studies demonstrated that pharmacist-led interventions significantly increased ADR notifications. Education campaigns, standardized reporting protocols, and enhanced integration of AM into clinical practice can strengthen AM pharmacovigilance efforts.

Conclusions: This review highlights the need to implement structured AM training programs and develop systematic evaluation frameworks to assess the effectiveness of AM labeling in improving pharmacovigilance practices. Further research is required to optimize AM strategies and reinforce pharmacists' role in post-marketing drug safety.

Purpose: To evaluate the risk of major congenital malformations (MCMs) associated with quinolone exposure during the first trimester of pregnancy using a large administrative database in Japan.

Methods: A large claims database was used from January 2005 to November 2019. The dates of pregnancy onset and delivery were estimated using the developed algorithm. MCMs were defined according to the International Classification of Diseases, 10th revision codes. The risk of MCM associated with first-trimester quinolone prescriptions was evaluated in women with infectious diseases diagnosed during the first trimester of pregnancy. We evaluated the overall risk of MCMs in infants, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by comparing women with first-trimester prescriptions of quinolones with those without antibiotic prescriptions, adjusting for covariates with propensity score overlap weights.

Results: The prevalence of first-trimester infectious diseases was 51.6% (47 121/91390). Among 47 121 women diagnosed with infectious diseases, 1 320 were prescribed quinolones during their first trimester of pregnancy. The overall prevalence of MCMs was 6.0% (2282/37766) in women unexposed to antibiotics and 5.9% (78/1320) in those exposed to quinolones. The first-trimester prescription of quinolone was not significantly associated with the overall MCM prevalence when overlap-weighted ORs (wOR) were calculated using propensity score overlap weights for covariates (wOR 0.904, 95% CIs 0.684-1.196).

Conclusions: Prescription of quinolones in the first-trimester of pregnancy was not associated with an increased risk of MCMs in infants. Our findings may support clinical decision-making when considering quinolone use during the first-trimester of pregnancy.

Purpose: The objective of this study was to compare the prescribing information for elderly patients on drug labels in Japan, the United States (U.S.), and Europe to suggest improvements in Japanese package inserts.

Methods: We surveyed drug labeling regulations in the three regions and selected 39 new drugs approved in Japan between 2012 and 2023 for diseases common in the elderly and approved in the U.S. and Europe. We examined the prescribing information for elderly patients such as dose adjustment instructions and comparison of safety profiles by age.

Results: The results revealed that 7.7% of Japanese package inserts provided dosage adjustment instruction for elderly patients, compared with 46.2% and 79.5% of U.S. and European drug labels, respectively. Regarding safety profile comparisons between age groups, 30.8% of Japanese package inserts included this information compared with 94.9% and 23.1% of U.S. and European drug labels, respectively. No Japanese package inserts listed the number of elderly patients included in clinical trials; whereas this information appeared on 89.7% of U.S. labels and 7.7% of European summaries of product characteristics.

Conclusions: Japanese package inserts provide less prescribing information for elderly patients than U.S. and European drug labels. To promote appropriate drug use among elderly patients in Japan, package inserts should be improved by incorporating sufficient information, such as clear dosage adjustment instructions and differences in safety profiles by age groups. These enhancements would align Japanese package inserts with international quality, providing healthcare professionals with more comprehensive drug prescribing information for treating elderly patients.

Purpose: Despite guideline warnings and concerns for increased mortality, acute ischemic stroke (AIS) survivors older than 66 years of age still receive benzodiazepines (BZDs). We examined the BZD-associated effect on mortality within 30 days post-discharge on survival among older Medicare beneficiaries after an AIS.

Methods: We analyzed a sample of Medicare beneficiaries enrolled for at least 12 months before hospitalization for AIS. Our primary exposure was BZD initiation within 30 days post-discharge, and its primary outcome was 90 days mortality risk differences (RDs) from discharge using trial emulation with methods to address confounding (i.e., cloning, weighting, censoring, and inverse-probability-of-censoring weighting).

Results: Of 47 421 beneficiaries, 826 (1.74%) initiated BZD 30 days post-discharge, and 6392 (13.48%) died within 90 days. The median age was 79 (IQR: 12), with 55.3% female, 82.9% White, 10.1% Black, 1.7% Hispanic, 2.2% Asian, and 0.4% American Native. After standardization (based on age, sex, race/ethnicity, length of stay, and baseline dementia), the 90-day mortality risk revealed an RD of 26 events per 1000 (95% CI: 22, 33). Subgroup analyses revealed higher RDs in older age groups, particularly those aged 86 or older, with an RD of 84 events per 1000 (95% CI: 73, 106), and for patients with baseline dementia, with an RD of 87 events per 1000 (95% CI: 63, 112).

Conclusion: Initiating BZDs within 30 days post-AIS discharge was associated with increased 90 days mortality risk, especially in older adults 76 years and older and those with baseline dementia, highlighting their vulnerability to BZD adverse effects.

Plain language summary: This study looked at how starting to take benzodiazepines (BZDs) affects survival in older adults after a stroke. BZDs are medications typically used for anxiety, insomnia, and seizures. The study focused on patients 66 years old and older on Medicare and determined whether taking BZDs within 30 days after leaving the hospital increased their risk of dying within 90 days. The study analyzed over 47,000 patients, selecting those with more favorable outcomes, and found that 1.74% began taking BZDs after their stroke. After adjusting for factors like age, gender, race, hospital stay, and dementia, we found that starting BZDs was associated with a higher risk of death. The risk was particularly high in patients 86 years and older and those with dementia. The study concluded that prescribing BZDs to older stroke survivors could substantially raise the risk of death, especially in the oldest and most vulnerable patients.

Objectives: To examine the comparative risk of malignancy, venous thromboembolism (VTE), and heart failure (HF) associated with biologic/targeted synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) in patients with rheumatoid arthritis (RA).

Methods: We conducted an observational cohort study using 3 US insurance claims databases: Medicare (2009-2019), MarketScan (2009-2020), and Optum's de-identified Clinformatics Data Mart Database (CDM, 2009-2022). We included adults with RA initiating abatacept (reference), tumor necrosis factor inhibitors (TNFi), rituximab, interleukin-6 inhibitors (IL-6i), or Janus kinase inhibitors (JAKi). We used an as-treated approach as the primary analysis to estimate outcome incidence. Inverse probability of treatment weighting was applied to adjust for confounding. Database-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox-proportional hazard models, then combined through random-effects meta-analysis.

Results: We identified 26 908 abatacept, 11 176 IL-6i, 115 437 TNFi, 14 045 JAKi, and 12 097 rituximab initiators. Weighted HR (95% CI) of malignancy was 0.73 (0.60-0.88) for IL-6i, 0.85 (0.60-1.19) for JAKi, 1.30 (1.14-1.49) for rituximab, and 0.93 (0.85-1.02) for TNFi, compared to abatacept. Weighted HR (95% CI) for VTE was 0.92 (0.62-1.35), 1.17 (0.73-1.86), 1.43 (1.50-1.95), and 1.16 (0.93-1.46), respectively. Weighted HR (95% CI) for HF was 1.00 (0.69-1.46), 1.24 (0.62-2.51), 1.52 (1.04-2.22), and 1.54 (1.22-1.94), respectively.

Conclusion: We observed increased risks of malignancy, VTE, and HF among rituximab initiators; an increased risk of HF among TNFi initiators; and a lower risk of malignancy among IL-6i initiators, all compared to abatacept initiators. These findings should be interpreted with caution due to the potential influence of residual confounding.