Triangulation of pharmacoepidemiology and laboratory science to tackle otic quinolone safety.
drug safety
pharmacoepidemiology
quinolones
real-world evidence
translation
triangulation
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
revised:
15
09
2021
received:
07
06
2021
accepted:
04
10
2021
pubmed:
7
10
2021
medline:
25
3
2022
entrez:
6
10
2021
Statut:
ppublish
Résumé
The scientific method requires studies with high internal and external validity. Though both are necessary, they do not go hand-in-hand: The more controlled a study is to enhance internal validity, the less applicable to real-world clinical care, and vice versa. In the many instances where evidence from clinical trials is not available, scientific inference must rely on more extreme approaches on this spectrum, such as mechanistic (limited generalizability/strong bias control) and real-world evidence (RWE) studies (higher generalizability/lesser bias control). Illustrate how triangulating mechanistic and RWE studies can enhance scientific inference by delivering the supporting evidence for both. We describe our research on an unexpected and highly unlikely drug safety issue: the risk of tympanic membrane (TM) perforations resulting from otic quinolone therapy. Tightly controlled laboratory studies using cell culture and rodent models were complemented with pharmacoepidemiological studies of real-world data to translate mechanistic findings and corroborate RWE. We present a cascade of mechanistic and RWE studies investigating fibroblast cytotoxicity, delayed healing of perforated TMs, and spontaneous TM perforations after otic quinolone exposure, all suggesting local tissue toxicity. Triangulation of mechanistic and RWE studies allowed incremental progress toward robust evidence on otic quinolone toxicity.
Sections du résumé
BACKGROUND
BACKGROUND
The scientific method requires studies with high internal and external validity. Though both are necessary, they do not go hand-in-hand: The more controlled a study is to enhance internal validity, the less applicable to real-world clinical care, and vice versa. In the many instances where evidence from clinical trials is not available, scientific inference must rely on more extreme approaches on this spectrum, such as mechanistic (limited generalizability/strong bias control) and real-world evidence (RWE) studies (higher generalizability/lesser bias control).
OBJECTIVES
OBJECTIVE
Illustrate how triangulating mechanistic and RWE studies can enhance scientific inference by delivering the supporting evidence for both.
METHODS
METHODS
We describe our research on an unexpected and highly unlikely drug safety issue: the risk of tympanic membrane (TM) perforations resulting from otic quinolone therapy. Tightly controlled laboratory studies using cell culture and rodent models were complemented with pharmacoepidemiological studies of real-world data to translate mechanistic findings and corroborate RWE.
RESULTS
RESULTS
We present a cascade of mechanistic and RWE studies investigating fibroblast cytotoxicity, delayed healing of perforated TMs, and spontaneous TM perforations after otic quinolone exposure, all suggesting local tissue toxicity.
CONCLUSION
CONCLUSIONS
Triangulation of mechanistic and RWE studies allowed incremental progress toward robust evidence on otic quinolone toxicity.
Identifiants
pubmed: 34611995
doi: 10.1111/bcpt.13668
pmc: PMC9298360
doi:
Substances chimiques
Quinolones
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-80Informations de copyright
© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
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