Displaying all 6 publications

Abstract:
Sort:
  1. Saffian SM, Duffull SB, Wright D
    Clin. Pharmacol. Ther., 2017 Aug;102(2):297-304.
    PMID: 28160278 DOI: 10.1002/cpt.649
    There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I(2) = 24%).
  2. Hatah E, Tordoff J, Duffull SB, Braund R
    Res Social Adm Pharm, 2014 Jan-Feb;10(1):185-94.
    PMID: 23688540 DOI: 10.1016/j.sapharm.2013.04.008
    In New Zealand, pharmacists are funded to provide adherence support to their patients via a service called "Medicines Use Review" (MUR). The service is based on the assumption that the medication regimen is clinically appropriate and therefore does not include a clinical review. However, whether or not pharmacists make clinical recommendations to patients during MUR is unclear.
  3. Saffian SM, Wright DF, Roberts RL, Duffull SB
    Ther Drug Monit, 2015 Aug;37(4):531-8.
    PMID: 25549208 DOI: 10.1097/FTD.0000000000000177
    The aim of this study was to compare the predictive performance of different warfarin dosing methods.
  4. Hatah E, Braund R, Tordoff J, Duffull SB
    Br J Clin Pharmacol, 2014 Jan;77(1):102-15.
    PMID: 23594037 DOI: 10.1111/bcp.12140
    The aim was to examine the impact of fee-for-service pharmacist-led medication review on patient outcomes and quantify this according to the type of review undertaken, e.g. adherence support and clinical medication review.
  5. Ng DPJ, Duffull SB, Faed JM, Isbister GK, Gulati A
    Clin Appl Thromb Hemost, 2018 May;24(4):669-676.
    PMID: 28731370 DOI: 10.1177/1076029617711802
    A well-accepted test for monitoring anticoagulation by enoxaparin is not currently available. As inadequate dosing may result in thrombosis or bleeding, a clinical need exists for a suitable test. Previous in silico and in vitro studies have identified factor Xa as an appropriate activating agent, and the phospholipid Actin FS as a cofactor for a Xa clotting time (TenaCT) test. A proof-of-concept study was designed to (1) explore the reproducibility of the TenaCT test and (2) explore factors that could affect the performance of the test. In vitro clotting time tests were carried out using plasma from 20 healthy volunteers. The effect of enoxaparin was determined at concentrations of 0.25, 0.50, and 1.0 IU/mL. Clotting times for the volunteers were significantly prolonged with increasing enoxaparin concentrations. Clotting times were significantly shortened for frozen plasma samples. No significant differences in prolongation of clotting times were observed between male and female volunteers or between the 2 evaluated age groups. The clotting times were consistent between 2 separate occasions. The TenaCT test was able to distinguish between the subtherapeutic and therapeutic concentrations of enoxaparin. Plasma should not be frozen prior to performing the test, without defining a frozen plasma reference range. This study provided proof-of-concept for a Xa-based test that can detect enoxaparin dose effects, but additional studies are needed to further develop the test.
  6. Saffian SM, Duffull SB, Roberts RL, Tait RC, Black L, Lund KA, et al.
    Ther Drug Monit, 2016 12;38(6):677-683.
    PMID: 27855133
    BACKGROUND: A previously established Bayesian dosing tool for warfarin was found to produce biased maintenance dose predictions. In this study, we aimed (1) to determine whether the biased warfarin dose predictions previously observed could be replicated in a new cohort of patients from 2 different clinical settings, (2) to explore the influence of CYP2C9 and VKORC1 genotype on predictive performance of the Bayesian dosing tool, and (3) to determine whether the previous population used to develop the kinetic-pharmacodynamic model underpinning the Bayesian dosing tool was sufficiently different from the test (posterior) population to account for the biased dose predictions.

    METHODS: The warfarin maintenance doses for 140 patients were predicted using the dosing tool and compared with the observed maintenance dose. The impact of genotype was assessed by predicting maintenance doses with prior parameter values known to be altered by genetic variability (eg, EC50 for VKORC1 genotype). The prior population was evaluated by fitting the published kinetic-pharmacodynamic model, which underpins the Bayesian tool, to the observed data using NONMEM and comparing the model parameter estimates with published values.

    RESULTS: The Bayesian tool produced positively biased dose predictions in the new cohort of patients (mean prediction error [95% confidence interval]; 0.32 mg/d [0.14-0.5]). The bias was only observed in patients requiring ≥7 mg/d. The direction and magnitude of the observed bias was not influenced by genotype. The prior model provided a good fit to our data, which suggests that the bias was not caused by different prior and posterior populations.

    CONCLUSIONS: Maintenance doses for patients requiring ≥7 mg/d were overpredicted. The bias was not due to the influence of genotype nor was it related to differences between the prior and posterior populations. There is a need for a more mechanistic model that captures warfarin dose-response relationship at higher warfarin doses.

Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links