Pharmacoepidemiology and Drug Safety最新文献

Purpose: To characterize long-term effects of COVID-19 among older adults (aged ≥ 65 years).

Methods: This retrospective descriptive study utilized Medicare Fee-for-Service beneficiaries' claims to characterize post-COVID condition diagnosis code usage, long COVID (defined as post-COVID condition diagnoses made ≥ 28 days after an initial COVID-19 diagnosis) incidence, patient demographics, and concurrent diagnoses.

Results: During April 1, 2020 to May 21, 2022, 193 691 (0.6%) of 31 847 927 Medicare beneficiaries were diagnosed with post-COVID conditions using ICD-10-CM diagnosis codes U09.9 and B94.8, regardless of prior COVID-19 diagnosis. Post-COVID condition diagnosis rate was higher among nursing home residents (18.7 per 1000 person-years) than community-dwelling beneficiaries (2.8). Among community-dwelling beneficiaries with a post-COVID condition diagnosis, 17.5% did not have any prior COVID-19 diagnosis code U07.1 recorded. Among beneficiaries with COVID-19 diagnosis, there were no significant sex, age, or race/ethnicity differences between those with post-COVID conditions ≥ 28 days after COVID-19 (i.e., long COVID) and those without post-COVID conditions. Certain myopathies and interstitial pulmonary disease codes were disproportionately present concurrently with long COVID compared to COVID-19.

Conclusions: In this large study of 32 million Medicare beneficiaries, we found approximately 194 000 post-COVID condition diagnoses. Post-COVID condition diagnosis rate was higher among nursing home residents, highlighting the substantial burden of COVID-19 in this vulnerable population. Community-dwelling beneficiaries were less likely to seek medical care for COVID-19 events than nursing home residents, which may suggest differences in COVID-19 severity and respiratory disease detection between these populations. Long COVID risk after COVID-19 infection may be similar across demographic groups.

Background: Drug shortages are an increasing and worldwide problem. Oral antibiotics are one of the most used medicines worldwide and have recently been affected by drug shortages. Despite this, little is known about the impact of antibiotic shortages on prescribing practices.

Aim: To explore the impact of oral antibiotic shortages on national antibiotic utilisation.

Methods: A cross-sectional study of oral antibiotic shortages and antibiotic utilisation was conducted using Australian reimbursement and regulatory data from January 2022 to December 2023. All nationally reimbursed oral antibiotics were included in the study. The number and duration of reported antibiotic shortages per product were determined for each active ingredient. The clinical impact was assessed using national utilisation in Defined Daily Doses per 100 000 inhabitants. Changes in trends were analysed using Joinpoint regression.

Results: Shortages were reported for eighteen of the twenty-one (86%) oral antibiotics reimbursed in Australia. For ten active ingredients, shortages did not coincide with changes in utilisation data. No clear relation between the number and duration of shortages and impact on utilisation was observed. Changes in utilisation coinciding with shortages were observed for eight active ingredients. For cefaclor (-20% decrease in utilisation) and roxithromycin (-26% decrease), the impact of shortages is most clearly reflected by decreases in utilisation. For the other six, minor changes in utilisation were observed coinciding with shortages.

Conclusions: Antibiotic shortages were common in Australia during 2022 and 2023. The impact of shortages differs per antibiotic, for some antibiotics there are shortages coinciding with declines in utilisation. For others, shortages occur without apparent changes in utilisation.

Purpose: The p.G12C mutation in KRAS is commonly found in many cancers and was previously untreatable until drugs like sotorasib were developed. However, up to 15% of patients treated with sotorasib have experienced hepatobiliary adverse events. To investigate whether these side effects are more common among sotorasib users, a pharmacovigilance study is necessary.

Methods: This study used the FDA adverse event reporting system (FAERS) database, a publicly available repository of reported drug adverse events, and AERSMine, an open-access pharmacovigilance tool, to investigate these adverse events.

Results: A total of 428 hepatobiliary adverse events were linked to sotorasib. Hepatic cytolysis had the highest reported relative risk at 26.541 and a safety signal of 4.726. Elevated liver and biliary enzymes such as AST, ALT, ALP, and GGT were commonly observed, but with lower reported relative risk and safety signal values, which supports previous real-world reports.

Conclusions: These findings highlight the hepatobiliary risks associated with sotorasib and underscore the importance of closely monitoring liver function in patients who are using the medication. This is particularly crucial for patients with hepatobiliary cancers, as disease progression and adverse events could be misinterpreted.

Background: During the pandemic, there was concern that underascertainment of COVID-19 outcomes may impact treatment effect estimation in pharmacoepidemiologic studies. We assessed the impact of outcome misclassification on the association between inhaled corticosteroids (ICS) and COVID-19 hospitalisation and death in the United Kingdom during the first pandemic wave using probabilistic bias analysis (PBA).

Methods: Using data from the Clinical Practice Research Datalink Aurum, we defined a cohort with chronic obstructive pulmonary disease (COPD) on 1 March 2020. We compared the risk of COVID-19 hospitalisation and death among users of ICS/long-acting β-agonist (LABA) and users of LABA/LAMA using inverse probability of treatment weighted (IPTW) logistic regression. We used PBA to assess the impact of non-differential outcome misclassification. We assigned beta distributions to sensitivity and specificity and sampled from these 100 000 times for summary-level and 10 000 times for record-level PBA. Using these values, we simulated outcomes and applied IPTW logistic regression to adjust for confounding and misclassification. Sensitivity analyses excluded ICS + LABA + LAMA (triple therapy) users.

Results: Among 161 411 patients with COPD, ICS users had increased odds of COVID-19 hospitalisations and death compared with LABA/LAMA users (OR for COVID-19 hospitalisation 1.59 (95% CI 1.31-1.92); OR for COVID-19 death 1.63 (95% CI 1.26-2.11)). After IPTW and exclusion of people using triple therapy, ORs moved towards the null. All implementations of QBA, both record- and summary-level PBA, modestly shifted the ORs away from the null and increased uncertainty.

Conclusions: We observed increased risks of COVID-19 hospitalisation and death among ICS users compared to LABA/LAMA users. Outcome misclassification was unlikely to change the conclusions of the study, but confounding by indication remains a concern.

Background and objectives: Based on the Adverse Event Reporting System (FAERS) data from the US FDA, this study mined the adverse drug reactions of obeticholic acid (OCA) in the real world and provided reference for clinical safe drug use.

Methods: Adverse event reports for OCA from the second quarter of 2016 to the third quarter of 2023 were extracted. The analysis for adverse reaction signal detection was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods.

Results: A total of 5661 OCA-related adverse event reports were collected, and 105 OCA-related adverse reaction signals were obtained, involving 14 systems, among which 46 new signals were not previously mentioned in the product labeling. Severe adverse event of OCA accounted for a relatively high proportion (1445 cases, 25.53%), among which the number of hospitalization reports was the largest (1042 cases, 18.41%). The top five adverse events were pruritus, fatigue, constipation, elevated blood alkaline phosphatase, and abdominal distention. The top five adverse reaction signals intensity were abnormal blood alkaline phosphatase, abnormal ratio of albumin globulin, spider nevus, combined with abnormal bilirubin, and γ-abnormal glutamyl transferase.

Discussion: Based on the pharmacovigilance study of the FAERS database, it is necessary to strengthen the clinical medication monitoring of OCA, so as to provide reference for effective pharmaceutical monitoring and rational clinical medication.

Introduction: Masking is a reporting bias where drug safety signals are muffled by elevated reporting of other medications in spontaneous reporting databases. While the impact of masking is often limited, its effect when using restricted designs, such as active comparators, can be consequential.

Methods: We used data from the US Food and Drugs Administration Adverse Event Reporting System (1999Q3-2013Q3) to study masking in a real-world example. Rosiglitazone, a thiazolidinedione with elevated reporting after safety concerns over cardiovascular risks, was the masking candidate. We hypothesized that stimulated reporting masked signals for another thiazolidinedione, pioglitazone. We computed estimates of proportional reporting ratios and information components, using the Bayesian confidence propagation neural network, for pioglitazone-myocardial infarction and pioglitazone-cardiac failure under unrestricted and active comparator designs, with and without the mask, before (1999Q3-2007Q1) and after (2007Q2-2013Q3) safety concerns. Relative change-in-estimates were computed to compare results with and without rosiglitazone.

Results: From 1999Q3-2007Q1, relative change-in-estimates of proportional reporting ratio for pioglitazone-myocardial infarction was 0.00 in unrestricted design and 0.10 in active comparator, and for pioglitazone-cardiac failure, the change was 0.01 and 0.62, respectively. From 2007Q2-2013Q3, relative change-in-estimates for pioglitazone-myocardial infarction was 0.41 in unrestricted design and 18.00 in active comparator; the change for pioglitazone-cardiac failure was 0.04 and 1.03, respectively. Relative changes in estimates of information component mirrored these trends.

Conclusions: Masking can influence signal detection in active comparator designs where external events impact reporting rates in reference sets. Evaluating masking in related contexts is essential for drug safety monitoring and resource allocation for follow-up studies.

Purpose: To describe the development of INSIGHT, a real-world data quality tool to assess completeness, consistency, and fitness-for-purpose of observational health data sources.

Methods: We designed a three-level pipeline with data quality assessments (DQAs) to be performed in ConcePTION Common Data Model (CDM) instances. The pipeline has been coded using R.

Results: INSIGHT is an open-source tool that identifies potential data quality issues in CDM-standardized instances through the systematic execution and summary of over 588 configurable DQAs. Level 1 focuses on conformance to the ConcePTION CDM specifications. Level 2 evaluates the temporal plausibility of events and uniqueness of records. Level 3 provides an overview of distributions, outliers, and trends over time to facilitate fit-for-purpose evaluation. Therefore, level 1 and 2 assure a proper data standardization, while level 3 provides information regarding the study population, and potential sub-populations. The DQAs are run locally and assessed centrally by a data quality revisor together with the data access provider's representatives.

Discussion: Data quality is the sum of several internal and external features of the data. While DQAs can provide reassurance about fitness-for-purpose for secondary-use data sources, improvements in data collection are essential to reduce errors and enhance overall data quality for Real World Evidence.

Conclusion: INSIGHT aims to support clinical and regulatory decision-making for medicines and vaccines by evaluating the quality of observational health data sources to support fit for purpose assessment. Assessing and improving data quality will enhance the reliability and quality of the generated evidence.

Study registration: This research was registered in EU PAS registration with number EU50142.

Purpose: Increases in adult stimulant prescribing pose a potential risk due to the higher prevalence of contraindicated conditions among this population. We sought to identify patient, provider, and visit characteristics predictive of potentially inappropriate adult stimulant prescriptions.

Methods: We conducted a repeated cross-sectional study using the National Ambulatory Medical Care Survey, a nationally representative weighted sample of 5 453 702 723 ambulatory care visits from 2012 to 2019. Potentially inappropriate prescriptions were defined as prescriptions to patients with potentially contraindicated conditions, as determined by US Food and Drug Administration stimulant labels.

Results: Of the 5 453 702 723 visits, stimulant use was prevalent at 121384694 (2.23%) visits and newly prescribed at 18880152 (0.34%) visits. Of these, 4 620 138 (24.47%) new stimulant prescriptions and 28 055 947 (23.11%) prevalent prescriptions were potentially inappropriate. Potentially inappropriate prescribing increased over time and with age. Visits to primary care providers (relative risk [RR] 1.65, 95% CI 1.05-2.59) were predictive of inappropriate prescribing. Non-Hispanic Black (RR 0.48, 95% CI 0.33-0.70) and Hispanic race/ethnicity (RR 0.46, 95% CI 0.35-0.60), coronary artery disease (RR 0.54, 95% CI 0.33-0.86), pregnancy (RR 0.05, 95% CI 0.03-0.11), hypertension (RR 0.69, 95% CI 0.56-0.84), and glaucoma (RR 0.07, 95% CI 0.02-0.24) were predictive of decreased prevalent stimulant prescriptions; substance abuse was predictive of new stimulant prescribing (RR 2.14, 95% CI 1.07-4.27).

Conclusions: The proportion of potentially inappropriate adult stimulant prescriptions increased over time and with patient age. Visits to primary care providers were predictive of potentially inappropriate prescribing, and a history of substance abuse was predictive of new stimulant prescriptions; therefore, quality improvement interventions regarding safe stimulant prescribing practices may be warranted.

Background: Cancer medicines usually have uncertain efficacy and safety profiles when they are first approved by medicines regulators because this evidence usually emerges post-market. Little is known about the extent to which post-market evidence is evaluated and integrated into evidence review processes in regulatory and clinical contexts.

Objectives: The objective of this scoping review is to examine the literature on how post-market evidence on benefits and harms is evaluated and integrated in regulatory decisions and guidance for clinical decision-making.

Methods: This scoping review focussed on the organisations that review cancer medicines and post-market evidence for their benefits and harms. It examined all regulatory or clinical contexts in which this post-market evidence might be included in evidence review processes for evaluation then integration into regulatory or clinical contexts. Four electronic databases were searched. Titles and abstracts were screened for all retrieved references followed by full-text screening by two independent reviewers according to pre-specified inclusion criteria.

Results: In total, 28 studies met inclusion criteria. These included 31 assessments by medicines regulators, four by clinical practice guideline developers and two by health technology assessment agencies. Half of the studies evaluated clinical outcomes for benefit or harms (e.g., overall survival, serious adverse events). We found that more published literature evaluated and integrated post-market evidence for benefits and harms of cancer medicines in regulatory than in clinical situations, such as treatment guidelines and health technology assessments. In these studies, post-market evidence for harms seemed to be integrated more often than for benefits. And the studies showed a gap: only some of the evaluated post-market evidence was subsequently integrated in both regulatory and clinical situations.

Conclusion: Overall, these findings raise important questions around the availability, accessibility, and assessment of post-market evidence for benefits and harms of cancer medicines so that it can be used by health professionals working in cancer services and by people with cancer.