RESUMEN
The FLT3 inhibitor quizartinib has been shown to improve overall survival when added to intensive induction chemotherapy ("7 + 3") in patients 18-75 years old with newly diagnosed AML harboring a FLT3-ITD mutation. However, the health economic implications of this approval are unknown. We evaluated the cost-effectiveness of quizartinib using a partitioned survival analysis model. One-way and probabilistic sensitivity analyses were conducted. In the base case scenario, the addition of quizartinib to 7 + 3 resulted in incremental costs of $289,932 compared with 7 + 3 alone. With an incremental gain of 0.84 quality-adjusted life years (QALYs) with quizartinib + 7 + 3 induction vs. 7 + 3 alone, the incremental cost-effectiveness ratio for the addition of quizartinib to standard 7 + 3 was $344,039/QALY. Only an 87% reduction in the average wholesale price of quizartinib or omitting quizartinib continuation therapy after completion of consolidation therapy and allogeneic hematopoietic cell transplant would make quizartinib a cost-effective option.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Benzotiazoles , Análisis Costo-Beneficio , Quimioterapia de Inducción , Leucemia Mieloide Aguda , Mutación , Compuestos de Fenilurea , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/economía , Leucemia Mieloide Aguda/mortalidad , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/economía , Quimioterapia de Inducción/métodos , Quimioterapia de Inducción/economía , Benzotiazoles/uso terapéutico , Benzotiazoles/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Persona de Mediana Edad , Adulto , Femenino , Anciano , Masculino , Adulto Joven , Años de Vida Ajustados por Calidad de Vida , Resultado del Tratamiento , Adolescente , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/economíaRESUMEN
BACKGROUND: 18F-flutemetamol uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and the confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like 18F-flutemetamol. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of 18F-flutemetamol to predict the progression from MCI to Alzheimer's disease dementia (ADD) or other dementias has not yet been systematically evaluated. OBJECTIVES: To determine the DTA of the 18F-flutemetamol PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD) or any form of dementia at follow-up. SEARCH METHODS: The most recent search for this review was performed in May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials.gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group's specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to the electronic searches. SELECTION CRITERIA: We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18F-flutemetamol scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. DATA COLLECTION AND ANALYSIS: We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. MAIN RESULTS: Progression from MCI to ADD was evaluated in 243 participants from two studies. The studies reported data on 19 participants with two years of follow-up and on 224 participants with three years of follow-up. Nine (47.4%) participants converted at two years follow-up and 81 (36.2%) converted at three years of follow-up.There were concerns about participant selection and sampling in both studies. The index test domain in one study was considered unclear and in the second study it was considered at low risk of bias. For the reference standard domain, one study was considered at low risk and the second study was considered to have an unclear risk of bias. Regarding the domains of flow and timing, both studies were considered at high risk of bias. MCI to ADD;Progression from MCI to ADD at two years of follow-up had a sensitivity of 89% (95% CI 52 to 100) and a specificity of 80% (95% CI 44 to 97) by quantitative assessment by SUVR (n = 19, 1 study).Progression from MCI to ADD at three years of follow-up had a sensitivity of 64% (95% CI 53 to 75) and a specificity of 69% (95% CI 60 to 76) by visual assessment (n = 224, 1 study).There was no information regarding the other two objectives in this systematic review (SR): progression from MCI to other forms of dementia and progression to any form of dementia at follow-up. AUTHORS' CONCLUSIONS: Due to the varying sensitivity and specificity for predicting the progression from MCI to ADD and the limited data available, we cannot recommend routine use of 18F-flutemetamol in clinical practice. 18F-flutemetamol has high financial costs; therefore, clearly demonstrating its DTA and standardising the process of the 18F-flutemetamol modality is important prior to its wider use.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Compuestos de Anilina/farmacocinética , Benzotiazoles/farmacocinética , Disfunción Cognitiva/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Anciano , Enfermedad de Alzheimer/metabolismo , Amiloide , Compuestos de Anilina/economía , Benzotiazoles/economía , Biomarcadores , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/metabolismo , Intervalos de Confianza , Progresión de la Enfermedad , Diagnóstico Precoz , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Radiofármacos/economía , Estándares de Referencia , Sensibilidad y Especificidad , Factores de TiempoAsunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Compuestos de Anilina/economía , Benzotiazoles/economía , Utilización de Medicamentos , Mercadotecnía , Ensayos Clínicos como Asunto , Diagnóstico Diferencial , Progresión de la Enfermedad , Aprobación de Drogas , Utilización de Medicamentos/economía , Humanos , Tomografía de Emisión de Positrones/economía , Tomografía de Emisión de Positrones/métodos , Trazadores Radiactivos , Estados Unidos , United States Food and Drug AdministrationAsunto(s)
Benzotiazoles/economía , Benzotiazoles/uso terapéutico , Indanos/economía , Indanos/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/economía , Anciano , Antiparkinsonianos/economía , Antiparkinsonianos/uso terapéutico , Análisis Costo-Beneficio , Agonistas de Dopamina/economía , Agonistas de Dopamina/uso terapéutico , Humanos , Cadenas de Markov , Modelos Económicos , Inhibidores de la Monoaminooxidasa/economía , Inhibidores de la Monoaminooxidasa/uso terapéutico , Pramipexol , Reino UnidoRESUMEN
BACKGROUND: Levodopa is the most effective treatment for the symptoms of Parkinson's disease (PD). However, after an initial period of benefit, several limitations become apparent, including motor complications such as dyskinesia. Dyskinesia can severely affect patients' quality of life and increases healthcare resource use. Thus, delaying the need for levodopa, and therefore the onset of levodopa-induced dyskinesia, is important. OBJECTIVE: The aim of this study was to compare the cost effectiveness, from a UK healthcare payer perspective, of two antiparkinsonian treatment strategies in early PD: first-line monotherapy with rasagiline, a novel monoamine oxidase B inhibitor; and the non-ergoline dopamine receptor agonist pramipexole. METHODS: An economic Markov model was developed as a pragmatic tool to derive comparative information on the effectiveness, utility and costs of these two strategies over a 5-year period. Model input data were obtained from the TEMPO study for rasagiline and from a study by the Parkinson Study Group for pramipexole. Effectiveness outcomes were time to levodopa and time to levodopa-induced dyskinesia. Cost and quality-adjusted life-year (QALY) data were derived from published sources. RESULTS: Rasagiline was the dominant strategy. Compared with pramipexole, use of the rasagiline strategy was estimated to reduce costs by 18% per patient over 5 years and was associated with an additional 10% delay in dyskinesia onset (0.41 years; 95% CI 0.27, 0.55). This strategy was also found to prolong the time to levodopa initiation by 25% through a gain of 0.83 levodopa-free years (95% CI 0.56, 1.1). In addition, use of the rasagiline strategy was found to generate a 5% gain in QALYs over 5 years compared with the pramipexole strategy (3.7 +/- 0.02 vs 3.51 +/- 0.03). Sensitivity analyses confirmed that the model was robust. CONCLUSIONS: Rasagiline represents a cost-effective alternative to pramipexole in the treatment of early PD in the UK.
Asunto(s)
Antiparkinsonianos/economía , Benzotiazoles/economía , Costos de la Atención en Salud , Indanos/economía , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Antiparkinsonianos/uso terapéutico , Benzotiazoles/uso terapéutico , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Progresión de la Enfermedad , Agonistas de Dopamina/economía , Agonistas de Dopamina/uso terapéutico , Femenino , Humanos , Indanos/uso terapéutico , Reembolso de Seguro de Salud , Masculino , Cadenas de Markov , Persona de Mediana Edad , Modelos Económicos , Inhibidores de la Monoaminooxidasa/economía , Inhibidores de la Monoaminooxidasa/uso terapéutico , Método de Montecarlo , Enfermedad de Parkinson/economía , Enfermedad de Parkinson/prevención & control , Pramipexol , Probabilidad , Años de Vida Ajustados por Calidad de Vida , Medicina Estatal , Resultado del Tratamiento , Reino UnidoRESUMEN
BACKGROUND AND PURPOSE: 1.3% of German adults suffer from clinically relevant restless legs syndrome (RLS). A cost-of-illness study was conducted to evaluate the costs for diagnosis and therapy of the idiopathic RLS. METHODS: A clinical pathway based on expert guidelines was developed. The costs for the 1st year of treatment in idiopathic RLS were calculated with the Markov Model. Relevant published clinical study data were used for the model as well as questioning of physicians. RESULTS: Costs per patient with approved drug treatment are 989.80 Euro for sickness funds and 1,285.26 Euro from the societal perspective. Drug costs are the main cost components for sickness funds and the society with 69% and 61%, respectively. Less than half of the patients continue an L-dopa therapy longer than 1 year. About one quarter of all RLS patients need off-label therapy after the 1st year of treatment. CONCLUSION: The costs for a guideline-oriented therapy for all patients with clinically relevant RLS in Germany are about 1,135 billion Euro, representing 0.5% of all health-related costs in Germany. Further controlled clinical trials are required to provide evidence for the efficacy of different treatment options including drugs without an approval for RLS and long-term use. Health services research is required for cost-utility analysis, to evaluate the costs of inadequate treatment, and to obtain additional information to improve the resource allocation in RLS treatment.
Asunto(s)
Costos de la Atención en Salud/estadística & datos numéricos , Programas Nacionales de Salud/economía , Síndrome de las Piernas Inquietas/economía , Factores Socioeconómicos , Benzotiazoles/economía , Benzotiazoles/uso terapéutico , Preparaciones de Acción Retardada , Dopaminérgicos/economía , Dopaminérgicos/uso terapéutico , Agonistas de Dopamina/economía , Agonistas de Dopamina/uso terapéutico , Costos de los Medicamentos/estadística & datos numéricos , Financiación Personal/economía , Alemania , Humanos , Indoles/economía , Indoles/uso terapéutico , Levodopa/economía , Levodopa/uso terapéutico , Cuidados a Largo Plazo , Cadenas de Markov , Modelos Económicos , Guías de Práctica Clínica como Asunto , Pramipexol , Asignación de Recursos/economía , Síndrome de las Piernas Inquietas/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: To estimate the cost-effectiveness of pramipexole versus no treatment and ropinirole in moderate to very severe idiopathic restless legs syndrome (RLS) in the UK and Sweden. METHODS: A Markov model was developed using clinical trial data for pramipexole and ropinirole. Model health states were based on the International RLS Study Group Rating Scale (IRLS) scores. Health states were: no (IRLS 0), mild (IRLS 1-14), moderate (IRLS 15-24), severe (IRLS 25-34), very severe RLS (IRLS 35-40) and death. Patients entered the model with an IRLS score > 15 matching the trial inclusion criteria of the pramipexole trials. Resource use and utilities were based on trial data, literature, a patient survey and a panel of physicians from the UK and Sweden in the absence of published information. A healthcare sector perspective was taken for the UK and a societal perspective for Sweden using 2004-2005 unit costs. The base case analysis took a 1-year timeframe. RESULTS: In the UK the incremental cost per quality-adjusted life year (QALY) for pramipexole was 3349 pounds sterling versus no treatment and a cost-saving of 92 pounds sterling against ropinirole. In Sweden, pramipexole produced cost-savings of Swedish Krona (SEK) 2381 (176 pounds sterling) versus no treatment and SEK 3564 (264 pounds sterling) against ropinirole. QALY gains in both countries were 0.095 versus no treatment and 0.007 versus ropinirole. Results compare well with UK cost-effectiveness thresholds of 20,000 pounds sterling/30,000 pounds sterling per QALY and are cost-saving for Sweden. One-way and probabilistic sensitivity analyses showed results to be robust. CONCLUSIONS: Pramipexole is cost-effective compared to no treatment and ropinirole for patients with moderate to very severe RLS.