The Prevalent New-User Design to Study Drug-Drug Interactions: The Example of Sulfonylureas and Warfarin Interaction on the Risk of Severe Hypoglycemia.
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引用次数: 0
Abstract
Purpose: The optimal design for pharmacoepidemiologic drug-drug interactions (DDIs) studies is unclear. Using the association between concomitant use of sulfonylureas and warfarin and the risk of severe hypoglycemia as a case study, a DDI with little or no clinical impact, we tested whether the prevalent new-user design can be applied in the area.
Methods: Among all patients initiating sulfonylureas in the UK's Clinical Practice Research Datalink (1998-2020), we identified those adding-on warfarin while on a sulfonylurea. For each co-exposed patient, we defined a prescription-based exposure set including other sulfonylurea users not adding-on warfarin (comparators). Within each exposure set, we matched each co-exposed patient to five comparators on time-conditional propensity scores (TCPS) and followed them using an as-treated approach. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of severe hypoglycemia associated with concomitant use of sulfonylureas and warfarin compared to use of sulfonylureas alone. Sensitivity analyses addressed the impact of different potential sources of bias.
Results: The study cohort included 17 890 patients co-exposed to sulfonylureas and warfarin and 88 749 matched comparators. After TCPS matching, patient characteristics were well-balanced between groups. Compared to use of sulfonylureas alone, concomitant use of sulfonylureas and warfarin was not associated with the risk of severe hypoglycemia (HR, 1.04; 95% CI, 0.92-1.17). Sensitivity analyses were consistent with the primary analysis (HRs ranging from 1.01 to 1.15, all not statistically significant).
Conclusions: Our study suggests that the prevalent new-user design could be used for the assessment of clinical effects of DDIs.
期刊介绍:
The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report.
Particular areas of interest include:
design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology;
comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world;
methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology;
assessments of harm versus benefit in drug therapy;
patterns of drug utilization;
relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines;
evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.