http://adisonline.com/pharmacokinetics/Abstract/publishahead/A_Bayesian_Dose_Individualization_Method_for.99925.aspx
Abstract
Background: Warfarin is a difficult drug to dose
accurately and safely due to large inter-individual variability in dose
requirements. Current dosing strategies appear to be sub-optimal, with
reports indicating that patients achieve international normalized ratios
(INRs) within the therapeutic range only 40-65 % of the time. The
consequences of poor INR control are potentially severe with INRs below 2
carrying an increased risk of clotting while INRs >4 increase the
risk of major bleeding events. Bayesian forecasting methods have the
potential to improve INR control.
Aims: The aims of this study were to (1) prospectively
assess the predictive performance of a Bayesian dosing method for
warfarin implemented in TCIWorks; and (2) determine the expected time in
the therapeutic range (TTR) of INRs predicted using TCIWorks.
Methods: Patients who were initiating warfarin therapy
were prospectively recruited from Dunedin Hospital, Dunedin, New
Zealand. Warfarin doses were entered into TCIWorks from the first day of
therapy until a stable steady-state INR (INRss) was achieved. The
predicted INRss values were determined using the first zero to six
serially collected INR observations. Observed and predicted INRss values
were compared using measures of bias (mean prediction error [MPE]) and
imprecision (root mean square error [RMSE]). The TTR was determined by
calculating the percentage of predicted INRss values between 2 and 3
when zero to six serially collected INR observations were available.
Results: A total of 55 patients were recruited between
March and November 2011. When no observed INR values were available the
resulting INRss predictions were positively biased (MPE 0.52 [95 % CI
0.30, 0.73]); however, this disappeared once observed INR values were
entered into TCIWorks. The precision of the predicted INRss values
improved dramatically once three or more observed INR values were
available (RMSE less than 0.53) compared with no INRs (RMSE 0.96). These
results suggest that TCIWorks will be effective at maintaining the INR
within the therapeutic INR range (2-3) 65 % of the time when three INR
measurements are available and 80 % of the time when six INR
measurements are available.
Conclusion: The TCIWorks warfarin dosing method produced
accurate and precise INRss predictions. We predict that the method will
provide an INR value within the therapeutic range 65-80 % of the time
once three or more INR observations are available, making this a useful
tool for clinicians and warfarin clinics. Further research to assess the
impact of this method on long-term INR control is warranted.
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