Pharmacoepidemiology and Drug Safety最新文献

Purpose: The use of common data models (CDMs) is increasing; however, the complexity of many CDM frameworks constitutes a barrier for their use. For many local and collaborative use cases, simpler CDMs can suffice. Here, we propose the EpiCore CDM, a simple CDM framework for use in Scandinavian pharmacoepidemiological studies.

Methods: The EpiCore CDM was developed based on a set of guiding principles. It should (i) accommodate the most common elements of typical data sources in the field and region, (ii) be accessible to users without needing advanced technical expertise or database infrastructure, (iii) prioritize structural and syntactic harmonization of data and defer clinical concept mapping to the analytical phase, (iv) be usable in both collaborative and single site settings, and (v) include support for quality control procedures.

Results: The EpiCore CDM comprises two mandatory administrative tables (person and observation), six optional event tables (diagnosis, procedure, encounter, drug, primcare, and cancer) and three optional lookup tables (drug_info, organisation_info, and prescriber_info). Each table, along with its columns and constraints is specified according to an EpiCore CDM specification template. This provides easy documentation and integrates with an R-package called EpiCoreAssistant, which provides quality control tools for testing the compliance of a CDM instance with the EpiCore specification. In the event that a project requires customization of the CDM, this is easily implemented in the template and testing. A step-by-step description is presented, demonstrating the steps involved in a typical CDM-based collaborative pharmacoepidemiological study using the EpiCore CDM.

Conclusions: We present the EpiCore CDM, a specification template and an R package that offers a simple framework for improved workflows, standardizations and collaboration, focused on Scandinavian pharmacoepidemiological studies and with relevance for a broad palette of register-based health care researchers.

Purpose: To study the effect of tricyclic antidepressant (TCA)/selective serotonin-norepinephrine reuptake inhibitor (SNRI) versus selective serotonin reuptake inhibitor (SSRI) on the risk of urinary tract infection (UTI) among people with multiple sclerosis (MS).

Methods: A case-control study was conducted using data from the UK Clinical Practice Research Datalink Aurum, nested within a cohort of people with MS. Each person with a UTI was matched to ≤ 4 controls on sex, region, age (±2 years), and time since MS diagnosis (±20%). Conditional logistic regression analyses were conducted to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) to compare TCA/SNRI to SSRI use and each antidepressant group to no antidepressant use. ORs were adjusted for smoking status, BMI, comorbidities, and recent drug prescriptions.

Results: Two thousand six hundred and sixty-four cases were matched to 3722 controls. TCA/SNRI versus SSRI use did not increase the risk of UTI (conditional aOR 1.21 [95% CI: 0.84-1.75]). TCA/SNRI use versus no antidepressant use did show an increased risk (conditional aOR [95% CI: 1.43 [1.21-1.69]), but SSRI versus no use did not (conditional aOR 1.15 [0.96-1.37]).

Conclusions: This study showed no increased risk of UTI for TCA/SNRI versus SSRI use among people with MS. However, effect estimates were imprecise due to small sample sizes.

Purpose: Observational comparative studies can be analyzed using intention-to-treat (ITT) (i.e., initial-treatment) or as-treated (AT) (i.e., per-protocol) approaches to estimate distinct treatment effects. Unfortunately, AT analyses have an increased vulnerability to selection bias from informative censoring. While methods for informative censoring adjustment are well established, the nuances of their implementation are less well documented.

Methods: We compared marginal hazard ratios for all-cause mortality from ITT and AT analyses comparing new users of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the clinical practice research datalink from 2019 to 2022 using inverse probability of treatment weights. We created inverse probability of censoring weights (IPCW) using (A) non-lagged and (B) lagged models to adjust for informative censoring in the AT analyses. We replicated analyses comparing acetylcholinesterase inhibitor and angiotensin receptor blocker initiators to assess the impact of IPCW in a different context.

Results: We identified 335 469 SSRI initiators and 24 318 SNRI initiators. While AT estimates (HR: 1.50, 95% CI: 1.30-1.74) were further from the null than ITT estimates (HR: 1.22, 95% CI: 1.12-1.32), applying IPCW attenuated AT estimates using both lagged and non-lagged models (lagged HR: 1.24, 95% CI: 1.08-1.44; non-lagged HR: 1.16, 95% CI: 1.00-1.33). In the 337 981 antihypertensive initiators, however, IPCW did not influence AT estimates.

Conclusions: Younger patients were more likely to discontinue SSRIs than SNRIs, resulting in biased AT estimates closer to estimates in older patients. IPCW attenuated this bias, highlighting the utility of weighting when censoring is linked to patient characteristics.

Objective: The COVID-19 pandemic caused disruptions in in-person mental health (MH) care and a rapid uptake of virtual MH care, but there is little research on the impacts of this on patients' ability to continue their MH medications. This study used population-level data to examine the impact of the pandemic on MH medication nonadherence.

Methods: This retrospective study used electronic health record and claims data to identify 149,977 patients with MH diagnoses at three U.S. health systems who filled at least one MH medication in the 9 months before and after 3/14/2020. The primary outcome was nonadherence to MH medications (i.e., a disruption in coverage ≥ 25%) during the pandemic.

Results: Pre-pandemic, 39% of patients had MH medication nonadherence, while 35% had nonadherence during the pandemic. Nonadherence during the pandemic improved for nearly all patient subgroups, with the exception of Black patients, for whom MH medication nonadherence increased from 47% to 49%. Asian, Black, and Hispanic patients were less adherent to MH medications during the pandemic than White patients, and patients with lower education or income were less adherent than patients with higher education or income. Non-rural patients were less adherent to MH medication than rural patients.

Conclusions: Adherence to MH medications improved during the pandemic for all subgroups except Black patients. Despite these improvements, disparities in MH medication adherence persisted for Asian, Black, and Hispanic patients and for patients with lower education or income, suggesting these populations may need additional outreach and support.

Purpose: Clopidogrel, an antiplatelet agent used to prevent ischemic events, may interact with proton pump inhibitors (PPIs), especially omeprazole and esomeprazole, and reduce its effectiveness. The evidence surrounding this interaction remains controversial. This study investigates whether co-prescribing clopidogrel with PPIs is associated with a higher incidence of major adverse cardiovascular events (MACEs) compared to clopidogrel monotherapy.

Methods: We conducted a retrospective cohort study analyzing data from the Real-world Evidence Research Network in Saudi Arabia from 2016 to 2023. Patients were followed from their initial clopidogrel prescription until the occurrence of MACEs or the end of follow-up. We employed stabilized inverse probability of treatment weighting (SIPTW) to adjust for potential confounders and the Cox proportional hazards model to assess risks.

Results: A total of 29 572 patients were included, with 21 480 in the clopidogrel + PPI group and 8092 in the clopidogrel-only group. Baseline characteristics were balanced post SIPTW, with similar mean ages (clopidogrel + PPI: 65.9 years; clopidogrel only: 66.1 years) and 64% male representation. The incidence rate of MACE was 3.22 versus 2.92 per 10 000 person-days in the clopidogrel + PPI and clopidogrel-only groups, respectively. The weighted hazard ratio for MACE was 1.20 (95% CI, 1.01-1.43).

Conclusions: In this large real-world cohort study, we observed a modest but statistically significant increase in the risk of MACEs among patients who received concomitant clopidogrel and proton pump inhibitor therapy. Given the widespread use of these medications, these findings emphasize the need for individualized risk assessments when co-prescribing PPIs and clopidogrel.

Background: Valproate-containing medicines (VPA) are first-line treatments for epilepsy; however, they pose teratogenic risks, restricting their use in women of childbearing age. We aimed to estimate the secular trends in the use of VPA and alternative treatments in young women, and to characterise dose/strength, treatment duration, and indication in new VPA users.

Methods: We conducted a multi-national population-based cohort study using primary care records from the Netherlands, Spain, and the UK (IPCI, SIDIAP, CPRD GOLD), primary and outpatient specialist care records from Germany and Belgium (IQVIA DA Germany, IQVIA LPD Belgium), and hospital records from Finland (ACI VARHA), all mapped to the OMOP Common data model. All women present in the databases aged ≥ 12 and ≤ 55 years on the 1st of January of each year in the period 2010-2022 (or latest available), with at least 365 days of prior observation, were included.

Results: A total of 2 948 860 (CPRD GOLD), 718 835 (IPCI), 2 494 052 (SIDIAP), 157 361 (ACI VARHA), 218 250 (IQVIA LPD Belgium); and 5 152 752 (IQVIA DA Germany) women were included. Among those, 6416, 1241, 10 398, 1447, 945, and 4002 started treatments with VPA, respectively. Incidence and prevalence of VPA use in young women decreased between 2010 and 2021, while the prevalence of the alternative treatments pregabalin and gabapentin increased, especially in CPRD (it rises from 0.5% to 1.5%). Median age of new VPA users ranged between 40 and 43 years. Anxiety and depressive disorder were frequent comorbidities, and the use of hormonal contraceptives we were able to capture was low. Average treatment duration varied substantially across databases.

Conclusion: Incidences and prevalence of use of VPA among young women declined since 2015. Conversely, alternative antiepileptics have increased in uptake, particularly gabapentinoids. The use of standardized federated analytics allowed for a rapid assessment of VPA utilization, supporting the regulatory agencies in their decision-making and improving patient safety across Europe.

Background: Clone-censor-weighting (CCW) can compare treatment regimens that are initially indistinguishable (such as starting treatment within specific time windows) without using landmarks or creating immortal time. The causal contrasts estimated in these cases and the analyses themselves can become quite complex; however.

Objective: Provide a tutorial on CCW for comparing initiation windows and illustrate the causal contrasts underlying such comparisons.

Methods: We identified patients with myocardial infarctions without past aspirin or clopidogrel use in Medicare's synthetic public data files. We assigned "clones" to three regimens: (1) initiation within 30 days; (2) initiation within 90 days; or 3) initiation from 30 to 90 days. Clones were censored when deviating from their assigned regimen by failing to initiate treatment in time or by initiating treatment too early. We addressed informative censoring using inverse probability of censoring weights (IPCW), calculated weighted 180-day risks of re-hospitalization or death using Kaplan-Meier methods, and visualized the portion of the population exposed during the first 90 days to compare exposure distributions underlying regimens.

Results: We identified 1589 patients experiencing myocardial infarction with no past medication use. 15% initiated within 30 days and 26% initiated between 30 and 90 days. After IPCW, the 180-day outcome risk was 40.2% in the 30-day regimen, 35.7% in the 90-day regimen, and 35.2% in the 30-to-90 day regimen.

Conclusions: Though CCW can be complex to implement and the effects it estimates can vary substantially across study populations that initiate treatments at different times, it is a useful tool for contrasting initiation windows.

Introduction: Despite substantial investments in analytical infrastructure and scientific research related to the development and analysis of real-world evidence in support of signal management, the impact on routine pharmacovigilance activities has been limited. Most organizations still rely largely on analyses of individual case reports and pre-existing evidence - especially during signal detection and validation.

Objective: This paper presents a set of recommendations for efforts to enable broader use of real-world evidence throughout pharmacovigilance signal management, in the future.

Outcome: The recommendations regard streamlined data access, data harmonization and use of reproducible analytical workflows to enable rapid and robust evidence generation. They emphasize the need for cross-disciplinary collaboration and for organizational adaptations to ensure adequate competence and supporting processes, including principles for how to integrate new types of evidence in decision-making. The execution of pilot studies under realistic conditions and the dissemination of their findings are highlighted as important steps toward defining the proposed change and driving progress in this area. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE).