Novel analysis of clinically relevant diagnostic errors in point-of-care devices.

BACKGROUND: To ensure proper clinical decision-making and avoid preventable harm, the quality of point-of-care (POC) device measures is routinely assessed. Traditional analyses may not reveal clinically important diagnostic errors. OBJECTIVES: To compare results between a novel analytic framework and traditional analyses. METHODS: Patients in four anticoagulation clinics provided two measures of the International Normalized Ratio (INR) at the same visit as part of routine quality assurance: one via a venous sample and one fingerstick. These were assessed with Hemochron POC devices. Traditional, quarterly, quality assurance assessments emphasized correlation analysis. The novel analysis used enhanced graphics and a validated assessment of clinical decision-making. RESULTS: 1518 paired INRs were analyzed. The correlation between the POC and laboratory assessments ranged between 0.84 and 0.91. Traditional quality assurance showed that the Hemochron devices were acceptable for continued use in each quarterly analysis. Enhanced graphical analysis demonstrated that the Hemochron devices never reported seven common INR values. The Hemochron devices systematically inflated values < 3 and deflated values > 4, biasing results towards the target INR range. Consequently, the Hemochron devices lead to a different clinical decision than the clinical laboratory measure in 31% of cases (458/1466; 95% confidence interval [CI] 29-34). When the reference INR was low, the Hemochron devices would not result in appropriate dose increases in 52% of cases (95% CI 48-56), placing these patients at risk for a significant adverse drug event. CONCLUSIONS: Our novel, clinically relevant analysis revealed previously undetected deficiencies in our POC INR devices, and our approach should be adopted by industry, regulators, and institutions.

Clinical decision-making as the basis for assessing agreement between measures of the International Normalized Ratio.

BACKGROUND: The now classic approach of Bland and Altman is often used to assess the level of agreement between International Normalized Ratio (INR) measures. However, we are concerned that this method does not define agreement in a clinically meaningful way. Agreement between measures should be characterized explicitly in terms of clinical decisions that result from INR measures. OBJECTIVES: To develop and validate an extension of the Bland-Altman method to assess agreement between INR measures, based explicitly on the way clinicians make decisions. METHODS AND RESULTS: We developed a clinically based graphical method to estimate the level of agreement between measures of INR. We identified clinically relevant INR ranges using epidemiologic and clinical evidence regarding risk and expected outcome at different INR ranges. Clinical decisions were expected to agree within these INR ranges and, therefore, the ranges became the basis for establishing agreement between measures. We used paired INR measures and resultant clinical decisions measured during a previous prospective study to validate and compare the accuracy of our model to those of Bland and Altman's and other published models. Our method more accurately predicts when warfarin dosing decisions differ than the Bland-Altman method (P < 0.02). Our method is also superior to other published methods, particularly at the important task of identifying when measures lead to discrepant clinical decisions. CONCLUSIONS: We introduced and validated an improvement of the Bland-Altman method to assess agreement between INR measures. Our model is superior because it is based explicitly on factors that influence clinical decision-making.

Using efficacy, safety, and cost data to support a formulary decision regarding thrombolytic therapy.

When urokinase was withdrawn from the market, alternative thrombolytics such as alteplase and reteplase needed to be evaluated for peripheral vascular disease (PVD). The efficacy, safety, and cost of these agents were evaluated formally by the Department of Pharmacy and presented to the Pharmacy and Therapeutics Committee. No published data support a difference in efficacy or safety between these agents. A cost analysis estimated the average total cost of care was higher for patients treated with reteplase ($4,556) compared with alteplase ($2,139). Therefore, alteplase was determined to be a more cost-effective thrombolytic agent to treat PVD.

Implementation and pharmacoeconomic analysis of a clinical staff pharmacist practice model.

The implementation and pharmacoeconomic analysis of a clinical staff pharmacist (CSP) practice model are described. Staff pharmacists at a large, tertiary care, academic medical center were selected and trained to perform clinical pharmacy services under the direction of clinical pharmacy specialist mentors. Clinical interventions by these CSP practitioners were evaluated in terms of direct cost savings (the difference in actual acquisition costs between therapies) and cost avoidance (the dollar value of adverse drug events [ADEs] avoided). The CSPs performed a total of 4959 interventions during a 12-month period. The interventions provided direct cost savings of $92,076 and an estimated cost avoidance of $488,436. Comparing cost savings and cost avoidance with the expenses of providing these services indicated a net economic benefit of $392,660. A new model of pharmacy practice that integrates staff pharmacists into existing clinical practice has the potential to minimize the risks, decrease the costs, and improve the outcomes associated with drug therapy.

A pharmacoeconomic appraisal of therapies for hepatitis B and C.

In the recent years, advances in the treatment of chronic hepatitis B and C have shown that newer, more expensive therapy may result in higher sustained viral response rates. In light of this, the pertinent question for healthcare decision-makers centres around whether this increase in efficacy 'justifies' the additional cost. Pharmacoeconomics is dedicated to helping answer these types of questions. In this article, we will discuss the clinical aspects of hepatitis B and C, recent advances in treatment and studies of the cost-effectiveness of these treatments.

Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients.

BACKGROUND: Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non-cystic fibrosis LTR and the interaction with cyclosporine (CSA). METHODS: Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine-2 (H-2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4-month period of time and compared using generalized estimating equations. RESULTS: The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p< or =0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019). CONCLUSIONS: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.

Cost effectiveness of interferon alpha2b combined with ribavirin for the treatment of chronic hepatitis C.

Treatment of chronic hepatitis C with Interferon (IFN) alpha2b monotherapy results in 10% to 15% sustained virological response (SVR). Combining IFN with ribavirin increases this response. In this analysis, using the Markov model, 6 treatment strategies for chronic hepatitis C (previously untreated) were compared on the basis of incremental cost per additional quality-adjusted life years ($/QALY). Our results showed that the no treatment strategy was associated with a cost of $38,747 and 13.10 QALYs. The strategy using IFN alone for 48 weeks was associated with a cost of $35,642 and 14.05 QALYs. The strategy using IFN monotherapy followed by combination therapy for nonresponders and relapsers was associated with a cost of $34, 561 and 15.53 QALYs. A similar strategy, but limiting combination to relapsers only, was associated with a cost of $34,758 and 14.40 QALYs. The strategy using IFN with ribavirin as the initial therapy for all patients was associated with a cost of $34,792 and 15.31 QALYs. Finally, the strategy using viral genotyping first and then adjusting the duration of combination therapy based on genotype was associated with a cost of $37,263 and 15.89 QALYs. The strategy using genotyping to guide duration of combination therapy was the most cost-effective approach with an incremental cost-effectiveness ratio of $7,500 per QALY. Sensitivity analyses confirmed the robustness of these results. We conclude that combination of IFN and ribavirin with duration of therapy based on the viral genotype, is a cost-effective approach in treating patients with chronic hepatitis C.