RESUMO
OBJECTIVES: To evaluate the impact of different dosages of topiramate (TPM) add-on to stable antiepileptic therapy for refractory partial epilepsy in adults. MATERIAL AND METHODS: Pooled intention-to-treat analysis of six similarly designed double-blind, placebo-controlled trials, including 481 patients treated with doses of TPM 200, 400, 600 and 800 mg/day, and 265 patients receiving placebo. RESULTS: Seizures were reduced by >/=50% from baseline in 41% of TPM-treated patients and 15% of placebo-treated patients (P < 0.001); 5 and 0.8%, respectively, were seizure-free (P < 0.003). TPM was significantly better than placebo regardless of gender, age, baseline seizure rate as well as number and type of concomitant antiepileptic drugs. Efficacy was statistically significant in favour of TPM at all dose levels: at least 50% seizure reduction was achieved in 40% of patients with 200 mg, 41% with 400 mg, 44% with 600 mg and 41% with 800 mg TPM when compared with 15% with placebo (P = 0.001 for each dosage arm vs placebo). The median reduction in monthly seizure frequency was 38%, 42%, 45% and 38% vs 8%, respectively (P = 0.001). Moreover, response to TPM was significantly superior to placebo at each of the dose levels tested for most of the baseline variables. The total percentage of withdrawals increased with the dosage, and the withdrawals caused by adverse events increased from 3% with placebo to 7% with 200 mg TPM (not significant vs placebo), 15% with 400 mg TPM (P = 0.08), 16% with 600 mg TPM (P = 0.002) and 15% with 800 mg TPM (P = 0.003). CONCLUSION: The efficacy of TPM add-on in partial epilepsy is consistent across efficacy endpoints and independent of study population characteristics. The response at 200 mg TPM is similar to the response at higher doses, but as drop-outs caused by adverse events are more frequent above the 200 mg dose, this pooled analysis supports that 200 mg daily is a good target dose for add-on therapy in most patients with partial epilepsy, showing an excellent balance between efficacy and tolerability.
Assuntos
Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Frutose/análogos & derivados , Frutose/administração & dosagem , Frutose/uso terapêutico , Adolescente , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Frutose/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , TopiramatoRESUMO
Long-term comparative trials among newer antiepileptic drugs are lacking; therefore decision models are needed to guide treatment decisions. The goal of this study was to develop an economic model of newly diagnosed epilepsy in the UK and to provide the first assessment of topiramate. A Markov model was developed combining data from clinical trials, cost-of illness, mortality, and utility studies. Expected costs and utilities associated with treatment strategies (first- and second-line treatments) were compared to find the cost-effectiveness frontier. First- and second-line monotherapy with topiramate or carbamazepine in partial seizures was less costly and more effective than other scenarios. In generalised seizures first-line topiramate was cost-effective with valproate or lamotrigine as second-line treatments depending on the set of utilities used. Models provide a relevant framework within which costs and health gains of antiepileptic drugs treatment options can be studied. Our findings are further evidence of the promising role of topiramate for patients with newly diagnosed epilepsy.
RESUMO
The problem of estimating expected outcomes for the economic evaluation of treatments for which the outcome of principal interest is (quality adjusted) survival time has so far not received sufficient attention in the literature. The best estimate of expected survival is mean survival time, but with censored survival data, the true survival time for all the subjects is not known, so the mean is not defined.A possible solution to this estimation problem is illustrated by a retrospective cost-effectiveness analysis of the addition of hormonal therapy to standard radiotherapy for patients with locally advanced prostate cancer. A recently proposed method is used to approach the problem caused by censored cost data, and the impact of uncertainty is assessed by bootstrap resampling techniques. Mean survival time is estimated by a restricted means analysis with the time point of restriction determined by statistical criteria. When average total costs and mean survival time is evaluated at this time point of restriction, the result is that the combined therapy (radiotherapy plus hormonal therapy) increases mean survival time by about 1 year, while reducing the costs per patient for the French health insurance system by 12 700 FF. The time point of restriction may also be determined by other criteria and mean survival time may be estimated by extrapolating the survival curves by means of various parametric survival distributions. We show that the exact results of the economic evaluation are decisively determined by the restriction time point chosen and the approach taken to estimate mean survival time.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante/economia , Gosserrelina/uso terapêutico , Custos de Cuidados de Saúde/estatística & dados numéricos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Anos de Vida Ajustados por Qualidade de Vida , Antineoplásicos Hormonais/economia , Análise Custo-Benefício , Custos de Medicamentos/estatística & dados numéricos , França , Gosserrelina/economia , Humanos , Masculino , Modelos Estatísticos , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/economia , Neoplasias da Próstata/patologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
We present a retrospective cost-effectiveness analysis using data from a randomised controlled trial (EORTC 22863) of the addition of early hormonal therapy with a luteinising hormone-releasing hormone (LHRH) analogue to radiotherapy in the treatment of patients with locally advanced prostate cancer. Data on the use of medical resources were extracted from the hospital charts of 90 patients recruited into the trial by one French hospital. Costs are assessed from the viewpoint of the French healthcare financing system and adjusted for censoring. Expected costs per patient of each treatment is related to the expected outcome, mean survival time, estimated by a restricted means analysis. The time point of restriction is determined by statistical criteria. In the base case analysis with a cut-off time point at 8.58 years, the combined therapy group (COMB) had a gain in mean survival time of 1.06 years (7.05 versus 5.99 years) and a reduction of average total costs of 12700 French francs (FF) (58300 FF versus 71000 FF). The analysis of uncertainty uses bootstrap techniques with 5000 replicates to examine the joint distribution of cost and survival outcomes. In 76% of the cases, COMB results in longer mean survival time and lower costs than the radiotherapy group (RT). In cases where COMB therapy raises costs (13% of the cases), it is rarely by more than 20000 FF per patient, no matter the size of the associated survival gain. It is thus highly likely that COMB should be considered a cost-effective option compared with RT for these patients. The exact result of the economic evaluation is decisively determined by the restriction time point selected for the determination of mean survival time, partly also because the average total costs of the two treatments develop entirely differently as a function of the survival time.
Assuntos
Antineoplásicos Hormonais/economia , Antineoplásicos Hormonais/uso terapêutico , Gosserrelina/economia , Gosserrelina/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Terapia Combinada , Análise Custo-Benefício/métodos , Seguimentos , França , Custos de Cuidados de Saúde , Humanos , Masculino , Neoplasias da Próstata/economia , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
With the aim of estimating and comparing the direct hospital costs of managing patients with advanced colorectal cancer in various countries, data on resource utilisation and unit prices were collected. Data on the consumption of medical resources were collected by a retrospective examination of the hospital charts for 20 patients in each of 10 centres in five European countries. To make cost comparisons meaningful, a complete and consistent set of unit prices for all the medical resources used in each of the countries would be required, but this could not be achieved. As an alternative method of comparison, the most complete set of unit prices (from Belgium) was used here to estimate the imputed average total cost of patient management in each centre. By using this approach, a summary index was created, which reflected only differences in resource utilisation. This index showed that there were considerable differences in the amounts of resources used for treating these patients, between, as well as within, countries. Differences of the same order of magnitude were found, when the treatment of subgroups of patients, according to site and stage of disease, were examined.