Pharmacoepidemiology and Drug Safety最新文献

Background: Preregistration of study protocols in a public repository promotes transparency and reproducibility in pharmacoepidemiological research. Despite its clear benefits, preregistration remains underutilized.

Purpose: Here, we discuss the advantages of preregistration, explore barriers to its implementation, and highlight existing repositories for preregistering real-world evidence study protocols. A relatively new option is the Real-World Evidence Registry within the Open Science Framework (OSF), which we briefly introduce.

Purpose: The Food and Drug Administration Adverse Event Reporting System (FAERS) is an important source of information on suspected adverse drug reactions, but does not standardise drugs. The Adverse Event Open Learning Through Universal Standardization (AEOLUS) System Provides Standardisation of drugs in FAERS to RxNorm, but its coverage leaves room for improvement and mapping accuracy has not been established. Furthermore, drugs are not mapped to the Anatomical Therapeutic Chemical (ATC) Classification System, which is frequently used in pharmacovigilance studies. Here we develop and evaluate the Aioli system, an extension of AEOLUS, to increase the mapping of drugs in FAERS to RxNorm, and to provide mappings to the ATC coding system.

Methods: Several changes and extensions were made to the AEOLUS mapping process to increase the number of drugs standardized to RxNorm. Information in FAERS fields about ingredient, route, dose amount, dose form, and dose unit was used to map to the most appropriate ATC code. Mapping accuracy was assessed on an evaluation set of 122 FAERS records.

Results: Aioli mapped 94.1% of drug names in FAERS to RxNorm, compared to 90.4% by AEOLUS. In addition, Aioli mapped 80.4% of drug names to ATC codes. Evaluation showed high accuracies, with 92.2% correct mappings to RxNorm and 94.0% to ATC.

Conclusions: We have developed and evaluated the Aioli system that maps drugs in the FAERS database to RxNorm and ATC codes. With increased coverage of drugs and the mapping to ATC, Aioli further improves the usability of FAERS data in pharmacovigilance studies.

Objective: Based on the FAERS database, this study aims to compare the safety of dabrafenib, trametinib, and their combination therapy, providing a reference for clinically safe medication.

Methods: Adverse event data for dabrafenib, trametinib, and their combination were extracted from the FAERS database. Descriptive statistical analysis was performed, and adverse event signals were mined using the Reporting Odds Ratio (ROR) method and the Bayesian Confidence Propagation Neural Network (BCPNN) method.

Results: The dabrafenib group yielded 11 048 adverse event reports with 311 positive signals across 22 organ systems. The trametinib group had 7848 reports with 249 positive signals across 21 organ systems. The combination therapy group had 13 544 reports with 418 positive signals across 23 organ systems. Signals were primarily concentrated in investigations, while adverse event reports mainly focused on general disorders and administration site conditions. The distribution of adverse events within System Organ Classes (SOCs) differed among the three groups.

Conclusion: Dabrafenib was associated with stronger reporting signals for adverse events such as fever, hyperpyrexia, and tumor progression. Trametinib was associated with skin-related or infectious adverse events like rash, acneiform dermatitis, and paronychia. The combination therapy increased the risk of ocular and cardiovascular adverse events. These signals indicate potential risks but require clinical confirmation. Clinical practice should prioritize monitoring different adverse events based on patient characteristics and drug type.

Purpose: This study assessed serious clinical outcomes comparing glucagon-like peptide 1 receptor agonists (GLP-1-RAs) with sodium glucose co-transporter 2 inhibitors (SGLT2-Is) in patients with type 2 diabetes (T2DM) and patients without diabetes using two chronic weight management (CWM) regimens.

Methods: We performed a new user, active comparator cohort study in a large, national U.S. claims database. Adults who initiated GLP-1-RAs, SGLT2-Is, naltrexone/bupropion (NalBup), or phentermine/topiramate (PhenTop) from 1 January 2016 to 31 December 2023 were included. Potential confounding was controlled using propensity score weighting for 82 clinical and demographic covariates, and risk ratios (RRs) were estimated.

Results: This study included 330,684 GLP-1-RA users and 264,277 SGLT2-I users with T2DM. Among CWM patients without diabetes, we studied over 25,000 GLP-1-RA users, 5019 NalBup users, and 3841 PhenTop users. In both indications, GLP-1-RA users had higher rates of hospitalizations for gallbladder and biliary diseases with RRs ranging from 1.14 (95% CI: 1.06-1.22) in T2DM patients to 3.32 (95% CI: 1.44-7.64) in CWM patients. No reduction in the rate of cardiovascular events was observed for GLP-1-RA users with RRs ranging from 0.92 (95% CI: 0.37-2.25) in CWM patients to 1.03 (95% CI: 0.99-1.08) in T2DM patients. In T2DM patients, GLP-1-RA users had a lower rate of acute liver injury (RR: 0.76; 95% CI: 0.64-0.91).

Conclusions: This study corroborates an increased risk of hospitalization for gall bladder and biliary conditions among users of GLP-1-RAs and found similar rates as comparators of MI or stroke when GLP-1-RAs were used for T2DM or CWM. This real-world study complements placebo-controlled trials and can further inform prescribing decisions.

Protocol registration: The study protocol was pre-registered at the Center for Open Science's Real-World Evidence Registry and is publicly accessible online (https://doi.org/10.17605/OSF.IO/PSY74).

Purpose: Owing to their rapid antipyretic effects and predictable pharmacokinetic properties, acetaminophen (AAP) are commonly administered intravenously to severely ill patients. However, the potential development of hypotension as a consequence of intravenous AAP administration has not been thoroughly addressed. In this study, we aimed to identify the risk factors associated with the occurrence of serious hypotension following intravenous AAP administration during fever in patients with hematologic malignancies.

Methods: This retrospective study included hospitalized patients in the hemato-oncology department. Patients were evaluated for serious adverse drug reactions (ADRs) resulting from intravenous administration of AAP between January and December 2023 at a tertiary hospital. The control group comprised patients who received intravenous AAP but did not experience hypotension. After univariable analysis, multivariable analysis was performed to identify the risk factors for serious hypotension.

Results: The serious hypotension group included 37 patients, while the control group had 111 patients randomized in a 1:3 ratio based on age and sex. Three risk factors were identified as increasing the likelihood of serious hypotension: body temperature prior to administration, acute kidney injury, and bacteremia. The mean arterial pressure prior to administration decreased the risk of developing serious hypotension by 0.96 times with an increase of 1 mmHg. There were no significant differences in the length of hospitalization or 90-day mortality between the two groups.

Conclusions: Given that patients with hematologic malignancies and associated risk factors may develop serious hypotension that can lead to death, it is essential to closely monitor blood pressure during intravenous administration of AAP.

Background: Interstitial lung disease (ILD)/pneumonitis is an important safety risk of trastuzumab deruxtecan (T-DXd) treatment. This study assessed the effectiveness of additional risk minimization measures (aRMMs) outlined in the educational material (EM) for the product regarding physicians' awareness, knowledge, and implementation related to the risk, early detection, and management of ILD/pneumonitis.

Methods: A web-based survey was conducted among prescribers of T-DXd from seven European countries (Austria, Denmark, France, Germany, Sweden, Spain, and the UK) between 03/2021 and 11/2022. The overall effectiveness of the aRMMs was determined as the percentage of physicians correctly responding to questions in the awareness, knowledge, and implementation domains, with cut-off thresholds of ≥ 80%, ≥ 60%, and ≥ 75%, respectively.

Results: Overall, 172 prescribing physicians from seven countries completed the survey questionnaire (response rate: 3.1%). The majority (73.8%) of the physicians acknowledged receiving EMs. In all, 91.6%, 46.7%, and 76.7% of the physicians correctly responded to questions in the awareness, knowledge, and implementation domains, respectively. The low score observed in the knowledge domain was primarily because the respondents did not acknowledge fever as a typical symptom of ILD/pneumonitis. When a post hoc sensitivity analysis was performed where "fever" was not classified as a mandatory answer to the question about typical symptoms for ILD/pneumonitis, the proportion of physicians achieving the threshold increased to 68.6%.

Conclusion: The aRMMs effectively imparted awareness and supported the management of T-DXd-induced ILD/pneumonitis.

Introduction: Many clinical data networks often focus on a single use-case or disease. By contrast, the TriNetX Dataworks-USA Network contains real-world clinical information that can be applied to multiple research questions and use cases. The purpose of this study is to describe the Network's characteristics, as well as its generalizability to the US population, particularly the healthcare-seeking population.

Methods: Using the Dataworks-USA Network, a large, regularly updated data network containing de-identified patient electronic health record (EHR) information from across the United States, basic demographics were summarized and compared to the US Census Bureau International Database (IDB) 2022 data and the National Cancer Institute's version of the Census Bureau's U.S. County Population Data for 2022 to examine the generalizability of the Network.

Results: Patients in the Dataworks-USA Network are approximately 5 years older than the Census, and the Network has a larger proportion of female patients. The Network has a lower proportion of patients identified as Asian and White race, and a higher proportion who identify as other relative to the Census; other races are similar between the two data sources (< 1% difference). Regionally, Dataworks-USA has a smaller proportion of patients in all race categories compared with the Census due to the larger proportion of patients of Unknown or Other race.

Conclusions: TriNetX's Dataworks-USA Network provides a robust data source for many use cases and is broadly generalizable to the US population, particularly the healthcare-seeking population, with differences related to the underlying nature of the data sources.

Objective: The objective of this study was to evaluate 12-month persistence of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) treatment in US patients with axial spondyloarthritis (axSpA) using real-world data, and patient baseline characteristics associated with increased or decreased persistence probability.

Methods: Anonymized US claims from Merative MarketScan provided patient data relative to an index date (initiation of a new b/tsDMARD of interest for axSpA), from which patients were followed for 12 months or until b/tsDMARD non-persistence (≥ 90-day gap or b/tsDMARD switch) or MarketScan disenrollment. Persistence probabilities were estimated using Kaplan-Meier survival curves. Association of variables with persistence was estimated using multivariable Cox regression analyses.

Results: Of the 5970 adults with axSpA, 76.7% were prescribed a TNFi as their index b/tsDMARD, and 55.1% were b/tsDMARD-unexposed while 44.9% were b/tsDMARD-exposed before index b/tsDMARD. b/tsDMARD persistence probability was 67.8%, 57.7%, and 54.4% at 6, 9, and 12 months, respectively. 12-month persistence probabilities stratified by index b/tsDMARD mode of action or history of b/tsDMARD treatment ranged from 51.8% to 55.7%. Female sex and history of dactylitis were associated with decreased b/tsDMARD persistence, while history of inflammatory bowel disease, uveitis, and obesity were associated with increased persistence probability.

Conclusions: Around half of patients studied were non-persistent with any given b/tsDMARD within a year of initiating therapy. Persistence was not considerably affected by index b/tsDMARD mode of action or history of b/tsDMARD treatment. Patient characteristics associated with decreased persistence probability, including female sex and dactylitis, may help clinicians recognize patients who may benefit from additional support to improve long-term treatment outcomes.

Background: Counseling women who are either pregnant or contemplating pregnancy on their use of prescribed drugs remains a major clinical challenge. Since the thalidomide tragedy in the 1960s, the use of drugs during pregnancy has been subject to widespread concern due to the potential for unwanted effects on the unborn child, notably major congenital malformations.

Objective: To examine the risk of major congenital malformations following first trimester exposure to all marketed prescription drugs in Denmark.

Study design: This was a population-based cohort study utilizing national health registries in Denmark. We studied all singleton livebirths in Denmark between January 1, 2004, and December 31, 2017, and we linked data from the National Danish Prescription Register, Birth Register, Patient Register, and Cause of Death Register. Using logistic regression analysis, we compared exposed liveborn to unexposed liveborn children while controlling for important confounders. The main outcome measure was major congenital malformations, and the secondary outcomes included organ-specific major congenital malformations as defined by EUROCAT.

Results: Of 326 drugs with at least 5 livebirths with major congenital malformations, 31 were associated with an increased risk of major congenital malformations compared to unexposed livebirths (adjusted Odds Ratio [aOR] ≥ 2.0). Compared to livebirths of women who discontinued treatment prior to pregnancy, 17 drugs with an increased risk (aOR ≥ 2.0) were identified. Among 115 drugs prescribed to ≥ 1000 women during the first trimester, only insulins had aORs ≥ 2.0 for overall major congenital malformations. There were > 100 drugs with no increased risk of major congenital malformations.

Conclusions: Using a complete nationwide dataset, > 100 null-associations between first-trimester drug exposure and overall major congenital malformations were documented. This provides important insights and reassurance to support pregnant women and inform shared decision making. We confirm previously known teratogenic drugs and other potential teratogenic drugs, clopidogrel and liraglutide, were identified. These latter associations should be addressed in future studies using disease-specific confounder control.