Empirical validation of the reverse parametric waiting time distribution and standard methods to estimate prescription durations for warfarin

Thrane, J.; Støvring, Henrik; Hellfritzsch, Maja; Hallas, Jesper; Pottegård, Anton

doi:10.1002/pds.4581

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…We estimated the duration of each dispensing using reverse parametric waiting time distribution [29, 30]. According to a validation study using warfarin as a case, which has a large interindividual variation in daily dose, this approach gives less bias and higher precision than traditional methods assuming a fixed daily dose [31]. The method considers the time from the last dispensing of each patient before an index time point, or reverse waiting time.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the method can take into account covariates predictive of the time from one dispensing to the next, such as age, sex and amount filled. This can reduce misclassification on the individual level [31]. In practice, we pooled all dispensings of a study drug to new users within the last year before 1 November 2015, and used their last filling in this time interval in a reverse parametric waiting time distribution model with 90th percentile interarrival distribution and adjustment for age, sex, and number of tablets dispensed.…”

Section: Methodsmentioning

confidence: 99%

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Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: A nationwide pharmacoepidemiological study

et al. 2019

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Objective To compare effectiveness and safety of warfarin and the direct oral anticoagulants (DOAC) dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation in routine care. Methods From nationwide registries, we identified treatment-naïve patients initiating warfarin, dabigatran, rivaroxaban or apixaban for non-valvular atrial fibrillation from July 2013 to December 2015 in Norway. We assessed prescription duration using reverse waiting time distribution. Adjusting for confounding in a Cox proportional hazards model, we estimated one-year risks for ischemic stroke, transient ischemic attack (TIA) or systemic embolism, major or clinically relevant non-major bleeding; intracranial; gastrointestinal; and other bleeding. We censored at switch of treatment or 365 days of follow-up. Results We included 30,820 treatment-naïve patients. Compared to warfarin, the adjusted hazard ratios (HR) for ischemic stroke, TIA or systemic embolism were 0.96 (95% CI 0.71–1.28) for dabigatran, 1.12 (95% CI 0.87–1.45) for rivaroxaban and 0.97 (95% CI 0.75–1.26) for apixaban. Corresponding hazard ratios for major or clinically relevant non-major bleeding were 0.73 (95% CI 0.62–0.86) for dabigatran, 0.97 (95% CI 0.84–1.12) for rivaroxaban and 0.71 (95% CI 0.62–0.82) for apixaban. Statistically significant differences of other safety outcomes compared to warfarin were fewer intracranial bleedings with dabigatran (HR 0.28, 95% CI 0.14–0.56), rivaroxaban (HR 0.40, 95% CI 0.23–0.69) and apixaban (HR 0.56, 95% CI 0.34–0.92); fewer gastrointestinal bleedings with apixaban (HR 0.70, 95% CI 0.52–0.93); and fewer other bleedings with dabigatran (HR 0.67, 95% CI 0.55–0.81) and apixaban (HR 0.70, 95% CI 0.59–0.83). Conclusion After 1 year follow-up in treatment-naïve patients initiating oral anticoagulation for non-valvular atrial fibrillation, all DOACs were similarly effective as warfarin in prevention of ischemic stroke, TIA or systemic embolism. Safety from bleedings was similar or better, including fewer intracranial bleedings with all direct oral anticoagulants, fewer gastrointestinal bleedings with apixaban and fewer other bleedings with dabigatran and apixaban.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: A nationwide pharmacoepidemiological study

et al. 2019

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“…For some medications, clinical input may be used to guide the duration of individual prescriptions (eg, assuming use of one defined daily dose or one tablet per day), or datadriven methods may be utilized, such as the parametric or reverse waiting time distribution. [99][100][101][102] Currently, all registries contain information on both reimbursed and non-reimbursed medications. However, until 2017, the Finnish registry recorded information only on reimbursed medications.…”

Section: Prescription Registriesmentioning

confidence: 99%

Nordic Health Registry-Based Research: A Review of Health Care Systems and Key Registries

Laugesen

Ludvigsson

Schmidt

et al. 2021

CLEP

285

230

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The Nordic countries are Denmark, Finland, Iceland, Norway, and Sweden and comprise a total population of approximately 27 million. The countries provide unique opportunities for joint health registry-based research in large populations with long and complete follow-up, facilitated by shared features, such as the tax-funded and public health care systems, the similar population-based registries, and the personal identity number as unique identifier of all citizens. In this review, we provide an introduction to the health care systems, key registries, and how to navigate the practical and ethical aspects of setting up such studies. For each country, we provide an overview of population statistics and health care expenditures, and describe the operational and administrative organization of the health care system. The Nordic registries provide population-based, routine, and prospective data on individuals lives and health with virtually complete follow-up and exact censoring information. We briefly describe the total population registries, birth registries, patient registries, cancer registries, prescription registries, and causes of death registries with a focus on period of coverage, selected key variables, and potential limitations. Lastly, we discuss some practical and legal perspectives. The potential of joint research is not fully exploited, mainly due to legal and practical difficulties in, for example, cross-border sharing of data. Future tasks include clear and transparent legal pathways and a framework by which practical aspects are facilitated.

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“…The Waiting Time Distribution approach is also data driven, but is based on a formal statistical model, which allows maximum likelihood estimation and explicit inclusion of covariates in the estimation [10]. The method has been validated for the oral anticoagulant warfarin, a drug with near chronic treatment, albeit with variable intensity [9].…”

Section: Discussionmentioning

confidence: 99%

“…It could therefore potentially aid in identifying discrepancies between actual and intended usage. The reverse WTD has been validated in simulation studies and empirically for warfarin treatment [8,9].…”

Section: Introductionmentioning

confidence: 99%

Persistence of statin treatment – the impact of analytic method when estimating drug survival

et al. 2021

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Background: There is ample evidence for several pharmaceutical treatments that adherence in terms oftreatment duration and dose is suboptimal. The actual drug intake cannot be observed directly in prescriptiondatabases, which only register drug redeemed and a limited number of patient characteristics. Consequently,the actual dose and duration of treatment must be inferred from observed redemptions. Persistence can thenbe expressed as treatment duration (also referred to as drug survival).Method: We used data from the Norwegian Prescription Database (NorPD) on redemptions of statins (ATCcodeC10AA) for the period 2010-2019 to explore three methods for determining prescription durations andin turn persistence (treatment duration): (i) The DDD-method using the number of DDD redeemed; (ii) Thedose-unit approach using the number of tablets redeemed; (iii) The reverse waiting time distribution method(WTD), which estimates prescription duration as the 90th percentile of the distribution within which patientsin ongoing treatment will have a new subsequent redemption. The three methods for estimating prescriptionduration were then used to estimate treatment duration using Kaplan Meier (KM) survival functions. For theDDD-method and the dose-unit approach we conducted sensitivity analyses assuming that one DDD or onetablet would last for 1.00, 1.25 or 2.00 days. We also tested the impact of grace periods in sensitivity analyses.Results: Treatment duration and drug survival varied substantially for the same patients depending on thechosen method, duration of a DDD or a tablet, and inclusion of grace periods. The 25th percentile of treatmentduration was 100 days for the DDD approach with one DDD per day, 100 days with the dose-unit approachwith one tablet per day and 453 days with the WTD approach.Conclusion: When estimating treatment duration from prescription databases one should be aware that thesemeasures of persistence are highly influenced by the chosen methodology. The choice of method should beinformed by the clinical context with a preference for use of methods based on a formal model.

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Empirical validation of the reverse parametric waiting time distribution and standard methods to estimate prescription durations for warfarin

Abstract: Comparing the different methods, the rWTD algorithm performed best and led to unbiased estimates of prescribed doses and thus prescription durations and reduced misclassification on the individual level upon inclusion of covariates.

Cited by 8 publications

References 23 publications

Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: A nationwide pharmacoepidemiological study

Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: A nationwide pharmacoepidemiological study

Nordic Health Registry-Based Research: A Review of Health Care Systems and Key Registries

Persistence of statin treatment – the impact of analytic method when estimating drug survival

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