Dataset Information

Use of Exposure Data to Establish Causality in Drug-Adverse Event Relationships: An Example with Desvenlafaxine.

ABSTRACT: Causality algorithms help establish relationships between drug use and adverse event (AE) occurrence. High drug exposure leads to a higher likelihood of an AE being classified as an adverse drug reaction (ADR). However, there is a knowledge gap regarding what concentrations are predictive of ADRs, as this has not been systematically studied. In this work, the Spanish Pharmacovigilance System (SEFV) algorithm was used to define the relationship between the AE occurrence and drug administration in 178 healthy volunteers participating in five desvenlafaxine single-dose clinical trials, a selective serotonin and norepinephrine reuptake inhibitor that may cause dizziness, headache, nausea, dry mouth, constipation and hyperhidrosis. Eighty-three subjects presented 172 AEs that were classified as possible (101), conditional (31), unrelated (24) and probable (16). AUC_∞ and C_max were significantly higher in volunteers with vs. without ADRs (5981.24 ng·h/mL and 239.06 ng/mL and 4770.84 ng·h/mL and 200.69 ng/mL, respectively). Six of 19 subjects with conditional AEs with an SEFV score of 3 points presented an AUC_∞ ≥ 6500 ng·h/mL or a C_max ≥ 300 ng/mL (i.e., above percentile 75) and were summed one point on their SEFV score and classified as "possible" (4 points), improving the capacity of ADR detection.

SUBMITTER: Rodriguez-Lopez A

PROVIDER: S-EPMC10819155 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Use of Exposure Data to Establish Causality in Drug-Adverse Event Relationships: An Example with Desvenlafaxine.

Rodríguez-Lopez Andrea A Mejía-Abril Gina G Zubiaur Pablo P Calleja Sofía S Román Manuel M Abad-Santos Francisco F Ochoa Dolores D

Pharmaceuticals (Basel, Switzerland) 20240103 1

Causality algorithms help establish relationships between drug use and adverse event (AE) occurrence. High drug exposure leads to a higher likelihood of an AE being classified as an adverse drug reaction (ADR). However, there is a knowledge gap regarding what concentrations are predictive of ADRs, as this has not been systematically studied. In this work, the Spanish Pharmacovigilance System (SEFV) algorithm was used to define the relationship between the AE occurrence and drug administration in ...[more]

PMID: 38256902

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Project description:Focality in electro-clinical or neuroimaging data often motivates epileptologists to consider epilepsy surgery in patients with medically-uncontrolled seizures, while not all focal findings are causally associated with the generation of epileptic seizures. With the help of Hill's criteria, we have discussed how to establish causality in the context of the presurgical evaluation of epilepsy. The strengths of EEG include the ability to determine the temporal relationship between cerebral activities and clinical events; thus, scalp video-EEG is necessary in the evaluation of the majority of surgical candidates. The presence of associated ictal discharges can confirm the epileptic nature of a particular spell and whether an observed neuroimaging abnormality is causally associated with the epileptic seizure. Conversely, one should be aware that scalp EEG has a limited spatial resolution and sometimes exhibits propagated epileptiform discharges more predominantly than in situ discharges generated at the seizure-onset zone. Intraoperative or extraoperative electrocorticography (ECoG) is utilized when noninvasive presurgical evaluation, including anatomical and functional neuroimaging, fails to determine the margin between the presumed epileptogenic zone and eloquent cortex. Retrospective as well as prospective studies have reported that complete resection of the seizure-onset zone on ECoG was associated with a better seizure outcome, but not all patients became seizure-free following such resective surgery. Some retrospective studies suggested that resection of sites showing high-frequency oscillations (HFOs) at >80Hz on interictal or ictal ECoG was associated with a better seizure outcome. Others reported that functionally-important areas may generate HFOs of a physiological nature during rest as well as sensorimotor and cognitive tasks. Resection of sites showing task-related augmentation of HFOs has been reported to indeed result in functional loss following surgery. Thus, some but not all sites showing interictal HFOs are causally associated with seizure generation. Furthermore, evidence suggests that some task-related HFOs can be transiently suppressed by the prior occurrence of interictal spikes. The significance of interictal HFOs should be assessed by taking into account the eloquent cortex, seizure-onset zone, and cortical lesions. Video-EEG and ECoG generally provide useful but still limited information to establish causality in presurgical evaluation. A comprehensive assessment of data derived from multiple modalities is ultimately required for successful management.

Dataset Information

Use of Exposure Data to Establish Causality in Drug-Adverse Event Relationships: An Example with Desvenlafaxine.

Publications

Use of Exposure Data to Establish Causality in Drug-Adverse Event Relationships: An Example with Desvenlafaxine.

Similar Datasets

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