RESUMEN
BACKGROUND: Dabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting. METHODS: Previously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RE-SONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving 1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of 20,000/QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at 2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at 33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving. CONCLUSION: From a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the Netherlands.
Asunto(s)
Antitrombinas/uso terapéutico , Análisis Costo-Beneficio , Dabigatrán/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Humanos , Modelos Teóricos , Países Bajos , Probabilidad , Tromboembolia Venosa/economíaRESUMEN
BACKGROUND: The aim of this study was to estimate the cost-effectiveness of tiotropium versus salmeterol to inform decision making within the Dutch healthcare setting. METHODS: A previously published, validated COPD progression model was updated with new exacerbation data and adapted to the Dutch setting by including Dutch estimates of healthcare use for COPD maintenance treatment and Dutch unit costs. Exacerbation data from the POET-COPD trial were combined with evidence from earlier tiotropium studies using Bayesian meta-analysis. The model-based analysis was performed using a one- and five-year time horizon. Main health outcomes were the number of exacerbations and quality-adjusted life years (QALYs). RESULTS: One-year costs per patient from the healthcare perspective were v1370 for tiotropium and v1359 for salmeterol; a difference of v11 (95% uncertainty interval (UI): -198-212). The annual number of exacerbations was 0.068 (-0.005-0.140) lower in the tiotropium group. The number of QALYs in the tiotropium group was 0.011 (-0.019-0.049) higher, resulting in an incremental cost-effectiveness ratio (ICER) of v1015 per QALY. After five years, the difference in exacerbations, QALYs and costs between the tiotropium and salmeterol group were -0.435 (-0.915-0.107), 0.079 (-0.272-0.520) and v-277 (-1586-1074), respectively, indicating that tiotropium was more effective and less costly. Using a societal perspective, tiotropium dominated salmeterol both after one and five years. CONCLUSION: Tiotropium reduced exacerbations and exacerbation-related costs. After one year the cost per QALY of tiotropium compared with salmeterol was very low, while after five years tiotropium was found to dominate salmeterol.
Asunto(s)
Albuterol/análogos & derivados , Broncodilatadores/economía , Enfermedad Pulmonar Obstructiva Crónica/economía , Derivados de Escopolamina/economía , Albuterol/economía , Albuterol/uso terapéutico , Broncodilatadores/uso terapéutico , Análisis Costo-Beneficio , Progresión de la Enfermedad , Humanos , Cadenas de Markov , Países Bajos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Años de Vida Ajustados por Calidad de Vida , Xinafoato de Salmeterol , Derivados de Escopolamina/uso terapéutico , Índice de Severidad de la Enfermedad , Bromuro de TiotropioRESUMEN
Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , Nevirapina/farmacocinética , Nevirapina/uso terapéutico , Oxazinas/farmacocinética , Oxazinas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/farmacocinética , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Alquinos , Fármacos Anti-VIH/sangre , Área Bajo la Curva , Benzoxazinas , Ciclopropanos , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Humanos , Lamivudine/sangre , Lamivudine/farmacocinética , Lamivudine/uso terapéutico , Masculino , Nevirapina/sangre , Oxazinas/sangre , Cooperación del Paciente , Modelos de Riesgos Proporcionales , Estudios Prospectivos , ARN Viral/sangre , Curva ROC , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de la Transcriptasa Inversa/sangre , Estavudina/sangre , Estavudina/farmacocinética , Estavudina/uso terapéuticoRESUMEN
AIMS: To develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified. METHODS: The pharmacokinetics of lopinavir in combination with ritonavir were described using NONMEM (version V, level 1.1). First, ritonavir data were fitted to a previously developed model to obtain individual Bayesian estimates of pharmacokinetic parameters. Hereafter, an integrated model for the description of the pharmacokinetics of lopinavir with ritonavir was designed. RESULTS: From 122 outpatients 748 lopinavir and 748 ritonavir plasma concentrations were available for analysis. The interaction between the drugs was described by a time-independent inverse relationship between the exposure to ritonavir over a dosing-interval and the apparent clearance (CL/F) of lopinavir. The model parameters volume of distribution and absorption rate constant were 61.6 l (95% prediction interval (PI) 22.4, 83.7) and 0.564 h(-1) (95% PI 0.208, 0.947), respectively. The model yielded a theoretical value for the CL/F of lopinavir without ritonavir of 14.8 l h(-1) (95%PI 12.1, 20.1), which translates to a value of 5.73 l h(-1) in the presence of ritonavir. The only factor with significant effect on the pharmacokinetics was concurrent use of non-nucleoside reverse transcriptase inhibitors (NNRTI), which increased the CL/F of lopinavir by 39% (P < 0.001). CONCLUSIONS: We have developed a model that has defined a time-independent inverse relationship between the exposure to ritonavir and the CL/F of lopinavir, and provided an adequate description of the pharmacokinetic parameters for the latter. Concomitant use of the NNRTIs efavirenz and nevirapine increased the CL/F of lopinavir.