A novel approach for pharmacological substantiation of safety signals using plasma concentrations of medication and administrative/healthcare databases: A case study using Danish registries for an FDA warning on lamotrigine

Wang, Wenyi; Battini, Vera; Carnovale, Carla; Noordam, Raymond; Dijk, Ko Willems van; Kragholm, Kristian; Heemst, Diana van; Soeorg, Hiie; Sessa, Maurizio

doi:10.1016/j.phrs.2023.106811

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…The study’s strengths lie in its population-based approach and the extensive analysis of a large number of subjects encompassing the entire Danish population [ 39 ]. Furthermore, the use of rigorous statistical methods effectively minimized residual confounding [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Comparing major and mild cognitive impairment risks in older type-2 diabetic patients: a Danish register-based study on dipeptidyl peptidase-4 inhibitors vs. glucagon-like peptide-1 analogues

Battini,

Barbieri,

Carnovale

et al. 2024

J Neurol

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Introduction The prevalence of major and mild cognitive impairment (CI) in type-2 diabetes older patients is 15–25% and 30–60%, respectively, thus affecting quality of life and health outcomes. There is, therefore, the need of head-to-head studies aiming at identifying the optimal treatment for individuals with type-2 diabetes at increased risk of mild and major CI. This study focuses on the risk of developing mild and major CI in Danish patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 analogues (GLP-1a) using administrative and healthcare registers. Methods An active comparator design with a 3-year follow-up period was used. The main outcome was the hospital admission with a diagnosis of mild CI or major CI. Multivariate Cox Regression analysis was performed using the high-dimensional propensity score to obtain adjusted Hazard Ratio (HR) estimates. Inverse probability of treatment weighting (IPTW) and marginal structured model were used to calculate risk differences while accounting for the variations of confounders throughout the follow-up period. Results Our results show a significant higher risk of major CI between DPP-4i and GLP-1a in unadjusted [HR (95% CI) = 3.13 (2.45–4.00), p < 0.001] and adjusted analyses [HR (95% CI) = 1.58 (1.22–2.06), p = 0.001]. No statistically significant differences were observed for mild CI. IPTW resulted stable throughout the follow-up period. Marginal structure modeling (β (95% CI) = 0.022 (0.020–0.024), p < 0.001) resulted in a higher risk of major CI for DPP-4i when compared to GLP-1a. Discussion DPP-4i was associated with an increased risk of developing major CI when compared to GLP-1a among older individuals with type-2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Comparing major and mild cognitive impairment risks in older type-2 diabetic patients: a Danish register-based study on dipeptidyl peptidase-4 inhibitors vs. glucagon-like peptide-1 analogues

Battini,

Barbieri,

Carnovale

et al. 2024

J Neurol

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“…An emerging use of DA is represented by the combination with other source of data, including in vitro/ex vivo assays to corroborate the biological plausibility (Salem et al, 2019), or electronic healthcare records (EHRs) to substantiate (or refuse) the research hypothesis or, under certain circumstances, to enhance signal detection for events with high background incidence (Pacurariu et al, 2015;Roberto et al, 2023;Wang et al, 2023). The correlation between disproportionality measures and pharmacokinetic/ pharmacodynamic features (e.g., lipophilicity, receptor affinity/ occupancy) may be used to explore the underlying pharmacological basis.…”

Section: Rationale For Conducting a Disproportionality Analysismentioning

confidence: 99%

Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems

Cutroneo,

Sartori,

Tuccori

et al. 2024

Front. Drug Saf. Regul.

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Spontaneous reporting systems remain pivotal for post-marketing surveillance and disproportionality analysis (DA) represents a recognized approach for early signal detection. Although DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient, their role remain irreplaceable for rapid detection of rare and unpredictable adverse drug reactions with strong drug-attributable component (e.g., designated medical events), especially when developed by a multidisciplinary team and combined with a careful case-by-case analysis (individual inspection of reports for causality assessment or to uncover reporting patterns and clinical features). In the recent past, a remarkable increase in publications of pharmacovigilance studies using DAs was observed, albeit the quality was debated: several publications contained “spin”, namely, misinterpretation of results to infer causality, calculate incidence, or provide risk stratification, which may ultimately result in unjustified alarm. The development of dedicated Guidelines by the international READUS-PV project (https://readus-statement.org/) will allow reproducible and transparent publication of accurate DAs, thus supporting their real transferability and exploitation by regulators and clinicians. This review offered a perspective on methodological aspects (and understanding) of DAs, their rationale, design, reporting, and interpretation.

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A novel approach for pharmacological substantiation of safety signals using plasma concentrations of medication and administrative/healthcare databases: A case study using Danish registries for an FDA warning on lamotrigine

Cited by 2 publications

References 37 publications

Comparing major and mild cognitive impairment risks in older type-2 diabetic patients: a Danish register-based study on dipeptidyl peptidase-4 inhibitors vs. glucagon-like peptide-1 analogues

Comparing major and mild cognitive impairment risks in older type-2 diabetic patients: a Danish register-based study on dipeptidyl peptidase-4 inhibitors vs. glucagon-like peptide-1 analogues

Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems

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