Importance of accounting for timing of time-varying exposures in association studies: Hydrochlorothiazide and non-melanoma skin cancer.
cumulative effects
flexible modeling
latency
time-varying exposure
weighted cumulative exposure
Journal
Pharmacoepidemiology and drug safety
ISSN: 1099-1557
Titre abrégé: Pharmacoepidemiol Drug Saf
Pays: England
ID NLM: 9208369
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
14
07
2023
received:
17
03
2023
accepted:
19
07
2023
medline:
14
11
2023
pubmed:
2
8
2023
entrez:
2
8
2023
Statut:
ppublish
Résumé
Hydrochlorothiazide (HCTZ), a widely prescribed antihypertensive drug with photosensitising properties, has been linked with non-melanoma skin cancer (NMSC) risk. However, previous analyses did not fully explore if and how the impact of past HCTZ exposures accumulates with prolonged use and/or depends on time elapsed since exposures. Therefore, we used different models to more comprehensively assess how NMSC risk vary with HCTZ exposure, and explore how the results may depend on modeling strategies. We used different parametric models with alternative time-varying exposure metrics, and the flexible weighted cumulative exposure model (WCE) to estimate associations between HCTZ exposures and NMSC risk in a population-based cohort of HCTZ users over 65 years old, in the province of Ontario, Canada. Among 3844 HCTZ users, 273 developed NMSC during up to 8 years of follow-up. In parametric models, based on all exposures, increased duration of past HCTZ use was associated with an increase of NMSC risk but cumulative dose showed no systematic association. Yet, WCE results suggested that only exposures taken 2.5-4 years in the past were associated with the current NMSC hazard. This finding led us to re-define the parametric models, which also confirmed that any HCTZ dose taken outside this time-window were not systematically associated with NMSC incidence. Our analyses illustrate how flexible modeling may yield new insights into complex temporal relationships between a time-varying drug exposure and risks of adverse events. Duration and recency of antihypertensive agents exposures must be taken into account in evaluating risk and benefits.
Substances chimiques
Hydrochlorothiazide
0J48LPH2TH
Antihypertensive Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1411-1420Subventions
Organisme : Canadian Institutes of Health Research (CIHR) Drug Safety and Effectiveness Network
ID : TD3-137716
Organisme : Canadian Institutes of Health Research (CIHR) Drug Safety and Effectiveness Network
ID : DMC-166262
Organisme : Canadian Network for Advanced Interdisciplinary Methods for Comparative Effectiveness Research
Informations de copyright
© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
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