Pharmacoepidemiology, Volume 4, Issue 2 (June 2025) – 4 articles

Background: The validated Screening Tool of Older People’s Prescriptions (STOPP) identifies potentially inappropriate prescribing (PIP)—treatments where potential risk outweighs potential benefit. STOPP is particularly important for people aging with HIV and comorbidities, since PIP may exacerbate symptoms and decrease adherence. Methods: We analyzed data from the DC Cohort, a longitudinal cohort of people with HIV (PWH). We applied STOPP criteria to identify PIP among DC Cohort participants aged ≥ 50 years who completed a Patient Reported Outcomes (PROs) survey. All medications prescribed in the 2 years prior to PROs survey completion were considered. Negative binomial models were used to evaluate factors associated with PIP and structural equation modeling was used to evaluate whether symptom burden mediates the relationship between PIP and quality of life. Results: Of 1048 eligible DC Cohort participants, 486 (46%) had at least one PIP. The most common systems implicated were musculoskeletal (23%), analgesic drugs (16%), and the central nervous system (13%). Age, race/ethnicity, HIV transmission factor, social determinants of health, and type of HIV care site were significantly associated with number of PIP in the crude models. In the multivariable model with just demographic variables, the association between age (aIRR: 1.03 (95% CI: 1.02, 1.04)), intravenous drug use (aIRR: 1.68 (95% CI: 1.20, 2.35)), White, non-Hispanic race (aIRR: 0.67 (95% CI: 0.50, 0.92)), site type (aIRR: 0.75 (95% CI: 0.62, 0.92)), and the expected number of PIPs remained significant. In the fully adjusted multivariable model with demographics and SDOH, the association between age, intravenous drug use, White, non-Hispanic race, and expected number of PIPs remained significant. Statistical evidence that symptom burden mediates the relationship between PIP and each of the QOL dimensions was present. Conclusions: Future interventions should work to decrease PIP among these high-risk groups, especially for PIP associated with increased symptom burden. Full article

Background: Incretin mimetics, including glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonist) and dipeptidyl peptidase-4 (DPP-4) inhibitors, have been increasingly utilized for glycemic control in patients with type 2 diabetes (T2D). Studies have demonstrated additional improvements in weight loss, cardiovascular health, and renal outcomes. Animal studies have shown an association between GLP-1 receptor agonists and C-cell proliferation and elevated calcitonin, resulting in an FDA black box. Insulin resistance in patients with T2D, along with the use of other glucose control medications, confounds the relationship between incretin mimetics and thyroid cancers. The true effect of incretin mimetics on thyroid cancer remains uncertain and speculative due to this confounding. Methods: This retrospective cohort study compared patients with T2D, who were new users of incretin mimetics, to new users of metformin. Study patients used no other anti-diabetes medications beyond the study medications. The risks of incident thyroid cancer and subsequent thyroidectomy were quantified using Cox proportional hazards regression models fitted with adjustments for demographic and medical covariates over a three-year study period. Medullary thyroid cancer (MTC) and multiple endocrine neoplasia type II (MEN2) cases were quantified. Results: Of the 91,394 patients, 28 incretin mimetic users had a diagnosis of thyroid cancer, and nine of these patients underwent a subsequent thyroidectomy procedure. No incretin mimetic user was diagnosed with MTC or MEN2. There was no statistically significant effect on the overall incretin mimetic category (1.28 aHR, 0.83–1.96), the incretin mimetic subcategories of GLP-1 receptor agonists (1.35 aHR, 0.80–2.29), or DPP-4 inhibitor (0.62 aHR, 0.33–1.17) users in developing thyroid cancer within three years of drug initiation. Similarly, no association was found between the overall incretin mimetic category (1.02 aHR, 0.49–2.10), the subcategories of GLP-1 receptor agonists (1.26 aHR, 0.54–2.96), or DPP-4 inhibitors (0.32 aHR, 0.08–1.37) and a subsequent thyroidectomy. Conclusions: In this real-world cohort study, exposure to incretin mimetics overall or through the incretin mimetic subcategories of GLP-1 receptor agonists and DPP-4 inhibitors was not associated with risks of thyroid cancer or thyroidectomy compared to metformin users. Full article

Objective: The aim of this study was to investigate a possible relationship between the time to onset (TTO) of adverse events following immunization (AEFIs) and recall bias and to compare it between AEFIs of COVID-19 vaccines reported though the spontaneous reporting system (SRS) and those from a cohort event monitoring (CEM) study. Methods: A retrospective study comparing TTO patterns of AEFIs of four COVID-19 vaccines from the SRS and those from a CEM study was performed. Reports concerning AEFIs related to COVID-19 vaccination were used for the study. TTO patterns were stratified for vaccination dose number, perceived burden of the AEFI, and for being pre-defined. Additionally, since menstrual disorders received much media attention, their effect on the TTO pattern was investigated for SRS reports only. Results: A total of 160,613 reports from the SRS and 19,979 from the CEM, containing 755,647 and 103,703 AEFIs, respectively, were included. For AEFIs with a short TTO, no differences in TTO patterns were observed. However, the median TTO for AEFIs from the SRS was lower with increasing TTO duration. There were differences in both median TTO and time to reporting for AEFIs reported before and during episodes of media attention, but no correlation between the two could be found. Conclusions: Based on the performed TTO analyses, recall bias does not seem to be more evident in SRS compared to CEM studies for AEFIs with a short TTO. For AEFIs with a longer TTO, this may be more pronounced. Full article

Background/Objectives: Controversy exists over the use of passive reporting systems, especially the Vaccine Adverse Event Reporting System, in risk assessment. One limitation of these systems is that adverse event (AE) reporting rates cannot be calculated without knowing the number of shots administered or prescriptions in the case of pharmaceuticals. Adverse event reporting rates can be a factor in a risk assessment, though they should not be solely relied on; they can be used to compare the relative safety profiles of different vaccine products or pharmaceuticals. This study introduces the Denominator-Adjusted Rate Estimates of Substance Adverse Events Frequency Evaluation (DARE-SAFE) method to analyze pharmacovigilance reporting rates for vaccines and common pharmaceuticals. Methods: We calculated reporting rates for the top 250 most prescribed drugs in the US Food and Drug Association (FDA) Adverse Event Reporting System and common vaccines in the Vaccine Adverse Events Reporting System. For vaccines, we used USA Centers for Disease Control (CDC) dose data and OpenVAERS reports. For pharmaceuticals, we utilized prescription data from ClinCalc and FAERS reports for 2022. Results: VAERS reporting rates varied significantly across vaccine types. COVID-19 vaccines showed a 63.0 ± 0.6 times higher rate of VAERS deaths per dose and an 18.95 ± 0.02 times higher rate of total adverse event reports per dose compared to influenza vaccines. The ratio of total VAERS reports to deaths for vaccines was 73 ± 4 to 1 (R² = 0.94). For pharmaceuticals, the ratio of total adverse event reports to deaths was 26 ± 2 (R² = 0.46), with a strong correlation between serious adverse events and deaths (ratio 9.1 ± 0.3, R² = 0.79). Conclusions: DARE-SAFE provides a standardized method for comparing reporting rates across different medical products. The observed differences between vaccines and pharmaceuticals, as well as among different vaccine types, warrant further investigation into reporting practices, actual safety profiles, and potential biases in surveillance systems. Full article