Changes in surrogate outcomes can be translated into clinical outcomes using a Monte Carlo model

Walraven, Carl van; Coyle, Doug; Taljaard, Monica; Forster, Alan J.

doi:10.1016/j.jclinepi.2009.01.015

Cited by 12 publications

(12 citation statements)

References 60 publications

(37 reference statements)

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“…Because their dataset was drawn from a randomized trial of dabigatran versus warfarin, they were able to show that, whereas sites with more algorithm-consistent warfarin dosing had lower rates of adverse events among patients receiving warfarin, they did not have lower rates of adverse events among patients receiving dabigatran. Some have expressed doubts about whether TTR really is in the causal pathway to outcomes, 5 suggesting that instead, sites with higher TTR also might be delivering high-quality care in other ways. If this were true, then quality improvement efforts aimed at increasing TTR might not achieve the desired benefits in terms of preventing adverse events.…”

Section: Article See P 2309mentioning

confidence: 99%

Improving the Management of Warfarin May Be Easier Than We Think

Rose

2012

Circulation

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Section: Article See P 2309mentioning

confidence: 99%

Improving the Management of Warfarin May Be Easier Than We Think

Rose

2012

Circulation

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“…Claims of effectiveness of genotype‐guided warfarin dosing have typically been based on INR‐related parameters, principally PTTR and time to therapeutic stable INR or warfarin dose. While there is a well‐documented relationship between the dose of warfarin and INR, the same cannot be said for the relationship between INR and clinical outcomes that matter . Most bleeding events in patients with AF receiving warfarin are reportedly not preventable despite careful INR control …”

Section: Discussionmentioning

confidence: 99%

Genotype‐guided warfarin therapy: Still of only questionable value two decades on

Shah

2020

J Clin Pharm Ther

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What is known and objective: Despite an apparently sound pharmacological basis, clinical studies of genotype-guided warfarin dosing have yielded mixed and conflicting results, leading to reluctance in its clinical implementation. The objective of this critique is to re-evaluate key warfarin pharmacogenetic studies with a view to explaining why this may be so. Methods:Major widely-cited warfarin pharmacogenetic studies as well as recent meta-analyses were identified and a critical analysis of these was undertaken to identify factors that may account for poor clinical implementation of pre-treatment genotyping. Results and discussion: Critical examination of major warfarin pharmacogenetic studies identified a number of methodological concerns such as marked variations in study designs with different variously-defined measures of outcome. Genotype testing involved only a limited number of CYP2C9/VKORC1 alleles. Claims of benefits of genotyping are based almost exclusively on INR-related parameters which are known to be highly time-labile and of limited value in predicting clinical risk orbenefit. This is evidenced by lack of any significant effect of genotyping on rates of bleeding or thromboembolic events. Neither have the effects of potential phenoconversion or medication non-adherence in study populations been adequately investigated. Although the effect of ethnicity/race is now better characterised, studies lack the power to determine whether any benefits claimed are indication-sensitive. What is new and conclusion:Since 60% of inter-individual variability in warfarin dose/ response is due to other factors (many of which are non-genetic), expectations of eliminating this variability simply by CYP2C9/VKORC1 genotyping are over-optimistic and efforts cost-ineffective. Real-world studies have not always corroborated trialsbased claims of clinical benefit. It is time to consider redirecting scarce resources away from the study of warfarin pharmacogenetics to pharmacogenetic research of potentially greater clinical relevance.

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“…Surrogate outcomes are physical signs or laboratory results that substitute for more definitive outcomes [11]. Because definitive outcomes occur so infrequently, when providers are asked to describe what they mean by high quality anticoagulation management, they are likely thinking more in terms of surrogate than definitive outcomes (i.e., they would find it unacceptable if patients with correctable causes of poor INR control were considered to have received high quality care simply because they were lucky enough not to have had major bleeding or a stroke) [7].…”

Section: Adverse Eventsmentioning

confidence: 99%

“…However, an ideal surrogate outcome would occur commonly, be easy to calculate, account for the underlying characteristics of the measured population and be convincingly linked to definitive outcomes [8]. As will [11]. Although the included trials had interventions that significantly improved TTR (mean increase was 8.4%; range 1.8-18%), these improvements translated to only small decreases in hemorrhagic and thromboembolic events (mean 0.66% per year; range 0.13-1.42%) that were not statistically significant.…”

Section: Measures Of Inr Controlmentioning

confidence: 99%

Quality measures and benchmarking for warfarin therapy

Witt

2011

J Thromb Thrombolysis

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The ultimate goal of warfarin therapy, to prevent thromboembolism with the lowest possible risk of major bleeding complications, is most likely to be realized when therapeutic anticoagulation as measured by the international normalized ratio (INR) is quickly achieved and maintained in appropriate candidates. Realizing this goal requires optimal functioning of various anticoagulation management system components. The extent to which these components function smoothly together determines the quality of warfarin therapy management. A quality measure is used to ascertain the degree to which a given system is successfully coordinating care to accomplish a particular therapeutic goal. The quality of care can be evaluated at different levels such as outcomes (e.g. INR results, major bleeding, thromboembolism, death), processes (e.g. method used to adjust warfarin doses), and structures (e.g. clinic organization structure, workload statistics). There is great need for a structured program of quality measurement for warfarin therapy management. The arrival of new options for oral anticoagulation medications increases the need for credible information regarding the site-specific quality of warfarin therapy management because the potential advantages over warfarin therapy associated with some of these agents are in part dependent upon the quality of warfarin therapy management.

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Changes in surrogate outcomes can be translated into clinical outcomes using a Monte Carlo model

Cited by 12 publications

References 60 publications

Improving the Management of Warfarin May Be Easier Than We Think

Improving the Management of Warfarin May Be Easier Than We Think

Genotype‐guided warfarin therapy: Still of only questionable value two decades on

Quality measures and benchmarking for warfarin therapy

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