Pharmacoepidemiology and Drug Safety最新文献

Background: Successful prevention of cardiovascular diseases (CVD) may reduce the burden of diseases. Preventive medication is an important measure to decrease the risks of cardiovascular events, in particular myocardial infarction and stroke. The aim of this study is to analyze the prevalence of CVD preventive medication in Germany over time with respect to sex and age and to compare it with the temporal development of strokes.

Methods: The study is based on statutory health insurance claims data from the AOK Niedersachsen (AOKN) covering the years 2005-2018. The study population comprises all AOKN insured persons aged 18 years and older (N = 2 088 495). Age-standardized time trends of the prevalence of CVD preventive medication and incidence of stroke were calculated for men and women in different age groups. After that, the relationship of both measures was examined in an ecological correlation.

Results: We found a clear increase in medication prevalence over time. In 2018, about 35% of the total population and about 85% of those over 85 years of age received CVD preventive medication. At the same time, age-standardized incidence rates of ischemic stroke were decreasing slightly. The ecological correlation showed a negative association between medication prevalence and stroke incidence especially in the higher age groups.

Conclusion: High correlation coefficients indicate that higher medication prevalence could be linked to better population health. Further research is needed to draw conclusions about the effects of increasing medicalization, including adverse risks and side effects at the population level.

Purpose: To assess adverse neurological risks following influenza vaccination in older adults.

Methods: Using a linked database of healthcare administrative claims data and vaccination records from an urban city in Japan (April 1, 2014, to March 31, 2020), we conducted an observational study utilizing a self-controlled case series design. We identified individuals aged ≥ 65 years who experienced adverse neurological outcomes, defined as hospitalizations related to epilepsy, paralysis, facial paralysis, neuralgia, neuritis, optic neuritis, migraine, extrapyramidal disorders, Guillain-Barre syndrome, or narcolepsy. We used conditional Poisson regression to analyze within-subject incidence rate ratios, comparing the risk of these outcomes during risk periods following influenza vaccination (0-6 days and 7-29 days after each vaccination) with nonvaccination periods. Our analysis was adjusted for age and season groups as time-varying covariates.

Results: We enrolled 3283 eligible individuals (men: 1643; mean [standard deviation] age: 76 [7.3] years). The incidence rate ratio for the outcome during the risk periods was 0.93 (95% confidence interval, 0.66-1.30) in risk period 1 (0-6 days after vaccination) and 1.14 (0.96-1.35) in risk period 2 (7-29 days after vaccination), respectively.

Conclusions: We found no evidence that the risk of adverse neurological events was increased after influenza vaccination in older adults. These results may help reassure older adults who are hesitant to receive influenza vaccination because of concerns regarding adverse neurological outcomes.

The German Cystic Fibrosis (CF) Registry (GCFR) is a national General Data Protection Regulation-compliant centralised database sponsored by the German Cystic Fibrosis Association (Mukoviszidose e.V.) and based on informed consent for each participating patient, ethical approval, and data protection votes. The aims of the GCFR are to optimise quality of care for CF at the centres, generate epidemiologic overviews, address research questions related to improved CF care, and inform caregivers, patients (aimed at patient empowerment), and health authorities and industry (aimed at care planning and pharmacovigilance). Established in 1995, the Registry has captured data on > 9600 individuals with a combined total of more than 140 000 annual assessments with an estimated coverage rate of > 90%. Patient data are collected after informed consent and confirmed diagnosis of CF, or a CFTR-related disorder, or a screening-positive inconclusive diagnosis of CF (i.e., CFSPID). The registry collects core, encounter, and annual health data. Data include demographics, anthropometrics, lung function, microbiology, CF-specific complications and chronic medications, hospitalisations, demand-oriented antibiotic therapies, and outcomes (death and transplants). Real world and pharmacovigilance studies have been published and additional research underway; there is a formal process for requesting access to the GCFR.

Purpose: Studies on antihypertensive treatment are important, as hypertension remains the major risk factor for cardiovascular morbidity and premature death. However, antihypertensive medicines are also used for other conditions, and the use of these medicines as a proxy for a diagnosis of hypertension might lead to misclassification in pharmacoepidemiological studies. This study aimed to investigate to what extent people dispensed antihypertensive medicines have been diagnosed with hypertension.

Methods: Cross-sectional study with data covering all healthcare and all dispensed prescriptions of antihypertensive medicines 2019 and diagnoses recorded 2015-2019 from the Stockholm Region, Sweden. Multinomial logistic regressions were used to assess the probability of having hypertension concerning age, sex, and antihypertensive drug class.

Results: A total of 386 860 individuals were included, 49% men, 12% incident users, and 80% of all had a recorded diagnosis of hypertension. In 73% of incident users, only one antihypertensive drug class was dispensed, as compared to 36% of prevalent users. A total of 38% of incident users and 9% of prevalent users had none of the diagnoses selected for the study recorded in any health record during 5 years. Prevalent and older users over the age of 65 from high (50%-79%) to very high (80% and more) probability of a recorded diagnosis of hypertension. Patients on antiadrenergic agents, high-ceiling diuretics, aldosterone antagonists, or beta receptor blockers had a lower probability of having a recorded diagnosis of hypertension than patients dispensed angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers.

Conclusion: Most patients dispensed antihypertensive medicines have a diagnosis of hypertension. However, caution is needed using data on dispensed medicines to classify incident antihypertensive users and younger patients as having a diagnosis of hypertension.

Introduction: The aim of this study is to use observational methods to evaluate reliability of evidence generated by a study of the effect of glucagon-like peptide 1 receptor agonists (GLP-1RA) on chronic lower respiratory disease (CLRD) outcomes among Type-2 diabetes mellitus (T2DM) patients.

Research design and methods: We independently reproduced a study comparing effects of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP4-i) on CLRD outcomes among patients with T2DM and prior CLRD. We reproduced inputs and outputs using the original study data (national administrative claims) and evaluated the robustness of results in comparison to alternate design/analysis decisions. To evaluate generalizability, we applied an analysis protocol and conducted a meta-analysis across a research network that includes a diverse array of populations and data sources. We also produced additional analyses evaluating individual drugs within the GLP-1RA class and CLRD outcomes.

Results: We confirmed alignment of study inputs and outputs and closely reproduced effect estimates and sensitivity analyses. Adjusted effect estimates were robust to empirical calibration. Network meta-analysis confirmed original findings but indicated weaker effects than originally published. Meta-analysis of drugs within the GLP-1RA class against DPP4-i provided evidence that effects vary within the GLP-1RA class, indicating stronger effects for exenatide and weaker effects of dulaglutide.

Conclusions: This study supports and establishes the reliability of the original study by (1) producing consistent findings in a range of alternate databases and populations, (2) demonstrating effects for multiple drugs within the GLP-1RA class, and (3) independently confirming the reproducibility of the original study and its findings. This reliability evaluation provides the beginnings of a broader framework for using standardized tools and distributed data networks to systematically interrogate the reliability of findings generated using observational data.

Purpose: To measure the impact of national regulatory actions implemented in France in August 2018 and June 2019 to reduce the risk of meningioma associated with the use of cyproterone acetate (CPA).

Methods: Using the French National Healthcare database, we calculated the monthly number of CPA users among cisgender women, men and transgender women in 2010-2021, the monthly proportion of users with cerebral imaging screening, and the annual rate of meningioma surgery associated with CPA use. CPA discontinuations and switches were analysed.

Results: Between 2018 and 2021, the number of individuals exposed to CPA fell by 85% (55 000 in August 2018 versus 7900 users of high-dose CPA in December 2021), corresponding to two waves of decrease in both use and initiation. This drop was greater among cisgender women (88%) than men (69%) or transgender women (50%). Cerebral imaging screening increased from 11% in June 2018 to 70% in June 2021 for ciswomen (13%-51% for men, 9%-60% for transwomen). After CPA discontinuation, no massive shift to a single product was observed, but, instead, dispersion towards other hormonal therapies. The overall annual rate of meningioma surgery associated with CPA exposure spectacularly decreased between 2017 and 2021 (-93% for ciswomen and -86% for men).

Conclusion: In France, high-dose CPA use sharply decreased after the implementation of national regulatory measures without a massive switch to other hormonal therapies. The increase in cerebral imaging screening did not result in an increase in meningioma surgery associated with CPA, but rather a massive drop of over 90%.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Purpose: Long-term opioid therapy (LTOT) has been shown to be associated with opioid overdose, but the definition of LTOT varies widely across studies. We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment.

Methods: Data were from a large private health insurance provider in North Carolina linked to mortality records from 2006-2018. Eligible patients were adults (18-64) newly initiating opioid therapy after a pain diagnosis or surgery. We defined LTOT as ≥ 1 opioid prescription per month totaling ≥ 60 days' supply within 90 days. We used inverse probability (IP)-weighted cumulative incidence functions to estimate three-year risk of opioid overdose and IP-weighted Fine-Gray models to estimate sub-distribution hazard ratios, comparing LTOT to short- to medium-term opioid therapy (SMTOT). We also examined modification by derived indication of acute pain or surgery versus chronic pain.

Results: We identified 491 369 patients, and 1.7% were exposed to LTOT. The three-year risk of opioid overdose was 0.3 percentage points (RD_w = 0.003, 95% CI: 0.001, 0.005) higher in LTOT patients compared to patients with SMTOT. The weighted hazard of opioid overdose was 4.4 times as high (HR_w 4.42, 95% CI 2.41, 8.11) among patients exposed to LTOT versus SMTOT. We did not find meaningful modification by clinical indication for opioid therapy.

Conclusions: Exposure to LTOT was associated with increased risk of opioid overdose in this population of privately insured patients using a rigorous definition of LTOT. These findings confirm the importance of guidelines to minimize duration of opioid therapy whenever possible.

Purpose: Real-world evidence (RWE) is increasingly considered in regulatory and health technology assessment (HTA) decision-making, though perspectives on its relevance may vary. Expanding on a recent review regarding regulatory decisions, this study aimed to identify factors influencing the need for RWE in HTA decision-making, confirm and enrich factors with stakeholder views, and evaluate similarities and differences between regulatory and HTA needs.

Methods: Previous scoping review methodology was used to identify factors influencing the need for RWE in HTA decision-making. Semi-structured interviews with stakeholders were conducted to confirm and enrich literature-derived factors for both regulatory and HTA contexts. Insights from the reviews and interviews were combined to explore similarities and differences in RWE needs across these domains.

Results: The HTA review, featuring 118 articles, revealed two major themes and six subthemes, encompassing 45 factors. The need for RWE depended on (1) questions addressable with RWE, and (2) contextual factors. Stakeholder interviews confirmed literature-derived factors. While contextual factors aligned between regulatory and HTA decision-making, question-related factors partly differed. Unlike the benefit-risk assessment in regulatory decision-making, RWE serves as direct input for the HTA, and involves specific details and a broader scope. Regulators require RWE for orphan status submissions, alternative approval pathways and to evaluate the impact of risk minimization measures, whereas HTA uses RWE to guide comparator selection, evaluate treatment implementation, quality of care and general healthcare impacts.

Conclusion: Contextual factors that influence the need for RWE are similar between regulatory and HTA decision-making, with variations seen in questions addressable with RWE.

Background: Patient and public involvement (PPI) in research is required to improve the relevance, feasibility, and interpretability. However, research on PPIs in pharmacoepidemiology (PE) is still limited. This study aimed to provide an overview of PPI implementation in pharmacoepidemiology through an environmental scan.

Methods: The environmental scan combined systematic reviews and expert interviews. A systematic review was conducted in MEDLINE, EMBASE, and the Cochrane Library from January 1, 2010, to June 30, 2023, to identify PE studies in which PPIs were mentioned. An additional review covered British Medical Journal's (BMJ) original articles from January 1, 2019, to June 30, 2023, via a similar method. In parallel, a cross-sectional study was conducted with a standardized questionnaire for French PE research teams, involving interviews via videoconference.

Results: We identified 3615 references for screening, among which 232 were selected for full-text screening. However, no studies have reported the use of PPIs in PE studies. The additional BMJ review identified 1058 references, 74 of which met the full-text selection criteria, and eight were included. Of 13 French PE research teams surveyed, three had prior PPI experience, and 12 affirmed the relevance of PPI in PE. The respondents identified barriers such as PE's complexity (n = 9). They suggested training for patients (n = 9) and collaboration with specialist teams (n = 5) to facilitate PPI.

Conclusion: Our environmental scan highlighted the emergence and relevance of PPIs in PE studies, even though they are still uncommon. Tools are needed to acculture and assist PE researchers in engaging in PPIs.