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PURPOSE: This exploratory analysis assessed and compared patients' treatment satisfaction with empagliflozin plus metformin versus glimepiride plus metformin, using data obtained from the Diabetes Treatment Satisfaction Questionnaire, status version (DTSQs) collected in a randomized, double-blind, double-dummy clinical trial. METHODS: Observed values for DTSQs scale score and each of its eight items were summarized by visit and treatment arm. Changes from baseline in these scores were analyzed using linear mixed models for repeated measures. RESULTS: The baseline scale score and item scores were comparable between empagliflozin plus metformin (n = 765) and glimepiride plus metformin (n = 780). Compared with baseline, patients reported significant treatment satisfaction increases and significant decreases in perceived hyperglycemia with both treatments at all visits. Also, compared with baseline, a significant increase in perceived frequency of hypoglycemia was observed in the glimepiride treatment group at all visits. No statistically significant treatment difference was observed in DTSQs scale score and its items at week 104. The difference between the treatment groups was significant and in favor of empagliflozin from week 28 onward for perceived frequency of hyperglycemia (P ≤ 0.006) and perceived frequency of hypoglycemia (P ≤ 0.011). CONCLUSIONS: Despite positive trends in favor of empagliflozin, there was no significant difference in DTSQs scale score between empagliflozin and glimepiride at 104 weeks. However, when compared with glimepiride, empagliflozin demonstrated significantly lower perceived frequency of hyperglycemia and hypoglycemia at all visits from week 28 onward. This finding is consistent with the clinical results reported for the EMPA-REG H2H-SU trial.
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Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Satisfacción Personal , Calidad de Vida/psicología , Compuestos de Sulfonilurea/uso terapéutico , Adulto , Compuestos de Bencidrilo/efectos adversos , Protocolos Clínicos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glucósidos/efectos adversos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hiperglucemia/inducido químicamente , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Compuestos de Sulfonilurea/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) are widely used in asthma research; however, in studies of newer asthma treatments, mean improvements in these measures compared with placebo arms do not exceed the minimal important difference (MID), particularly when a new treatment is added to current treatment. OBJECTIVE: We performed a systematic review and network meta-analysis to examine the magnitude of AQLQ and ACQ responses achieved with commonly used asthma drugs and factors influencing these end points in clinical trials. METHODS: A systematic literature search was conducted to identify blinded randomized controlled trials reporting AQLQ or ACQ results. Mixed treatment comparisons, combined with meta-regression, were then performed. RESULTS: Of the 64 randomized controlled trials (42,527 patients) identified, 54 included the AQLQ and 11 included the ACQ as end points. The presence of a run-in period, the nature of treatment during the run-in period, concurrent treatment during the treatment period, and instrument version significantly influenced the change in AQLQ score from baseline and whether it exceeded the MID. When compared with placebo, only inhaled corticosteroids (ICSs), with or without a long-acting ß-agonist, achieved the MID. The ACQ results were comparable with those of the AQLQ: no differences from placebo exceeded the MID, and ICS-based treatments provided the greatest improvements. CONCLUSION: The established within-patient MID for the ACQ and AQLQ is not achievable as a group-wise efficacy threshold between treatment arms in clinical studies in which controllers are added to ICS treatment. Thus in addition to reporting mean changes of the instruments, other measurement criteria should be considered, including responder analyses.
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Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Administración por Inhalación , Adulto , Animales , Femenino , Humanos , Masculino , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). METHODS: Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact-the upper bound of the values presented in the PBAC summary database-was categorized as ≤A$0, >A$0 up to A$10 million, A$10 million up to A$30 million, and >A$30 million per year. Descriptive, logistic, survival, and recursive partitioning decision analyses were used to estimate the relationship between the financial impact of a new drug indication and the recommendation for reimbursement. Multivariable analyses controlled for other clinical and economic variables, including cost per quality-adjusted life-year gained. RESULTS: Financial impact was a significant predictor of the recommendation for reimbursement. In the logistic analysis, the odds ratios of reimbursement for drug submissions with financial impacts ≥A$10 million to ≥A$30 million or >A$0 to
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Comités Consultivos
, Reembolso de Seguro de Salud
, Preparaciones Farmacéuticas/economía
, Australia
, Análisis Costo-Beneficio
, Seguro de Servicios Farmacéuticos
, Programas Nacionales de Salud
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BACKGROUND: Norm-based scores used to assess cognitive ability have clinical value when describing functioning of patients with neuronopathic disorders compared with unaffected, same-age peers. However, they have limitations when used to assess change in cognitive ability between two timepoints, especially in children with severe cognitive decline. Calculation of Projected Retained Ability Scores (PRAS) is a novel method developed to characterize absolute change in norm-based ability test scores. In this analysis, PRAS were calculated post hoc for children with mucopolysaccharidosis II (MPS II; Hunter syndrome) and early cognitive impairment in a 52-week phase 2/3 randomized controlled trial (RCT) and its extension study of intrathecal idursulfase (idursulfase-IT). Patients completing the first year of the extension after receiving idursulfase-IT in the RCT and extension (n = 32 of 34 enrolled) or the extension only (n = 15 of 15 enrolled) were categorized according to changes in Differential Ability Scales, Second Edition, General Conceptual Ability (DAS-II GCA) scores and PRAS at 1 and 2 years. Analyses were conducted in the overall population and a subpopulation aged < 6 years at baseline (idursulfase-IT in the RCT and extension [n = 27] and extension only [n = 12]). RESULTS: PRAS methodology differentiated patients with decreases in DAS-II GCA scores into three separate categories reflecting below-average cognitive growth rates, plateauing cognitive development, and deteriorating cognitive functioning. After 1 year in the RCT, 72.4% of patients who initiated idursulfase-IT had above-average or average cognitive growth rates in DAS-II GCA scores compared with 53.3% of those who did not receive idursulfase-IT; 6.9% versus 20.0% experienced deteriorating cognitive functioning. Similar results were seen in children aged < 6 years: 76% (idursulfase-IT group) versus 50% (no idursulfase-IT) had above-average or average cognitive growth rates in DAS-II GCA scores; 4% versus 17% had deteriorating cognitive functioning. The difference in the distributions of cognitive categories at 1 year in children aged < 6 years was significant (p = 0.048). At 2 years, the proportions of patients in different cognitive categories were more similar between treatment groups. CONCLUSIONS: PRAS methodology may help to differentiate changes in cognitive development in MPS II, and therefore may represent a valuable addition to existing approaches for interpreting changes in cognitive scores over time. TRIAL REGISTRATION: ClinicalTrials.gov NCT02055118 (registration date: 4 February 2014) and NCT02412787 (registration date: 9 April 2015).
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Iduronato Sulfatasa , Mucopolisacaridosis II , Niño , Humanos , Mucopolisacaridosis II/tratamiento farmacológico , Terapia de Reemplazo Enzimático/métodos , Iduronato Sulfatasa/uso terapéutico , CogniciónRESUMEN
BACKGROUND: Bardet-Biedl syndrome is a rare genetic disease associated with hyperphagia and early-onset, severe obesity. There is limited evidence on how hyperphagia and obesity affect health-related quality of life in patients with Bardet-Biedl syndrome, and on how management of these symptoms may influence disease burden. This analysis evaluated changes in health-related quality of life in adults and children with Bardet-Biedl syndrome in a Phase 3 trial following 1 year of setmelanotide treatment (ClinicalTrials.gov identifier: NCT03746522). METHODS: Patients with Bardet-Biedl syndrome and obesity received 52 weeks of treatment with setmelanotide and completed various self-reported health-related quality of life measures. Patients aged < 18 years or their caregiver completed the Pediatric Quality of Life Inventory (PedsQL; meaningful improvement, 4.4-point change); adults aged ≥ 18 years completed the Impact of Weight on Quality of Life Questionnaire-Lite (IWQOL-Lite; meaningful improvement range, 7.7-12-point change). Descriptive outcomes were reported in patients with data both at active treatment baseline and after 52 weeks of treatment. RESULTS: Twenty patients (< 18 years, n = 9; ≥ 18 years, n = 11) reported health-related quality of life at baseline and 52 weeks. For children and adolescents, PedsQL score mean change from baseline after 52 weeks was + 11.2; all patients with PedsQL impairment at baseline (n = 4) experienced clinically meaningful improvement. In adults, IWQOL-Lite score mean change from baseline was + 12.0. Of adults with IWQOL-Lite impairment at baseline (n = 8), 62.5% experienced clinically meaningful improvement. In adults, IWQOL-Lite score was significantly correlated with changes in percent body weight (P = 0.0037) and body mass index (P = 0.0098). CONCLUSIONS: After 1 year of setmelanotide, patients reported clinically meaningful improvements across multiple health-related quality of life measures. This study highlights the need to address the impaired health-related quality of life in Bardet-Biedl syndrome, and supports utility of setmelanotide for reducing this burden. Trial Registration NCT03746522. Registered November 19, 2018, https://clinicaltrials.gov/ct2/show/NCT03746522 .
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Síndrome de Bardet-Biedl , Calidad de Vida , Adolescente , Adulto , Humanos , Niño , Obesidad , HiperfagiaRESUMEN
PURPOSE: The validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment. METHODS: We conducted a systematic literature review of mCRC phase 2 and 3 clinical trials that reported OS and PFS (or time-to-progression [TTP]) data. Correlation between endpoints (either PFS alone or PFS aggregated with TTP [PFS_TTP]) was estimated within treatment arms. Treatment effect was the ratio of the median time to OS, PFS, or PFS_TTP in the "control" versus "experimental" arm. We conducted meta-regression analyses and performed receiver-operating characteristic (ROC) analysis. RESULTS: We analyzed data from 62 articles (23,527 patients). A high positive correlation was found between median PFS_TTP and median OS within treatment arms (r = 0.87; 95% confidence interval [CI], 0.82-0.91) and also between the median OS and median PFS (r = 0.89, 95% CI, 0.83-0.93)]. R(2) was 0.48 for PFS_TTP and 0.59 for PFS; R (2) for PFS_TTP was higher for first-line (R(2) = 0.54) than second-line studies (R(2) = 0.38). The ROC analysis is presented as a conceptual tool for evaluating the performance of PFS as a surrogate for OS at various thresholds. CONCLUSIONS: The correlation of PFS, alone or aggregated with TTP, with OS in clinical trials of patients with mCRC is robust across lines of therapy and provides a useful means of predicting improvements in OS using PFS data.
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Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Neoplasias Colorrectales/patología , Humanos , Metástasis de la Neoplasia , Curva ROC , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL). METHODS: Two pivotal Phase 3 trials explored the effect of setmelanotide on body weight and hunger in individuals with obesity due to POMC (NCT02896192) or LEPR (NCT03287960) deficiency. QOL and depression were investigated in parallel using the disease-specific, age-appropriate Impact of Weight on Quality of Life-Lite (IWQOL-Lite), Pediatric Quality of Life Inventory (PedsQL), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: In total, the POMC and LEPR trials enrolled 21 patients. Adults (≥ 18 years old; n = 7) had moderate-to-severe impairment in QOL at baseline, with mean (standard deviation [SD]) IWQOL-Lite total score 60.3 (13.2; maximum IWQOL-Lite total score = 100). The effect of setmelanotide on IWQOL-Lite total score was observed as soon as Week 5. Among those with scores at Week 52, 5 of 6 adults experienced a clinically meaningful improvement, with mean (SD) total scores increased from baseline by 24.2 (12.1) points. Children (6-12 years old; n = 2) and adolescents (13-17 years old; n = 4) had impaired QOL at baseline, with mean (SD) self-reported PedsQL total scores 53.3 (6.2) and 63.3 (29.1), respectively (maximum PedsQL total score = 100). Three of 5 patients experienced clinically meaningful improvement in PedsQL, with 2 children whose PedsQL total score increased by 28.3 and 3.3 points and 3 adolescents whose mean (SD) total score increased from baseline by 5.8 (18.3) points. Baseline mean (SD) PHQ-9 score (in those ≥ 12 years old) was 5.3 (3.8) and was generally maintained through Week 52. CONCLUSIONS: Patients with POMC or LEPR deficiency had impaired, and in some cases severely impaired, QOL before setmelanotide treatment. Setmelanotide improved QOL in patients as early as Week 5, with some patients no longer experiencing impaired QOL at Week 52. Improvements in QOL may be related to a reduction in hunger and body weight associated with setmelanotide. Because of the highly complex psychological consequences of rare genetic diseases of obesity, some patients may require a long period of treatment to improve QOL and benefit from interdisciplinary care.
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Proopiomelanocortina , Calidad de Vida , Adolescente , Adulto , Niño , Humanos , Obesidad/tratamiento farmacológico , Receptores de Leptina , Encuestas y Cuestionarios , alfa-MSH/análogos & derivadosRESUMEN
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions lead to chimeric tropomyosin receptor kinase (TRK) fusion proteins, which act as primary oncogenic drivers in diverse tumor types in adults and children. Larotrectinib, a highly selective and central nervous system-active TRK inhibitor, has shown high objective response rates, durable disease control, and a favorable safety profile in patients with TRK fusion cancer. The impact of larotrectinib on health-related quality of life (HRQoL) was evaluated in adult and pediatric patients in two phase I/II clinical trials (NAVIGATE; NCT02576431 and SCOUT; NCT02637687). Patients completed HRQoL questionnaires (EORTC QLQ-C30, EQ-5D-5L, and PedsQL) at baseline and at planned treatment cycle visits. Changes in questionnaire scores were evaluated over time, and by tumor type and treatment response. Questionnaires from 40 adult and 17 pediatric (2-19 years of age) patients receiving larotrectinib were completed at baseline and at least one post-baseline timepoint. Meaningful within-patient HRQoL improvements occurred at one or more timepoints in 60% of adults and 76% of pediatric patients. Sustained improvements in EORTC QLQ-C30 and PedsQL scores were rapid, occurring within 2 months of treatment initiation in 68% and 71% of patients, respectively. Improvements were observed regardless of tumor type and appeared to correlate with clinical efficacy. The rapid within-patient HRQoL improvements in adult and pediatric patients with TRK fusion cancer are consistent with the clinical profile of larotrectinib. Our results provide valuable information for use of this agent in this patient population. A plain language summary of this article is available in the supplementary appendix.
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Neoplasias/tratamiento farmacológico , Neoplasias/psicología , Pirazoles/farmacología , Pirimidinas/farmacología , Calidad de Vida/psicología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Neoplasias/genética , Inhibidores de Proteínas Quinasas , Proteínas Quinasas/genética , Receptor trkA/genética , Encuestas y Cuestionarios , Resultado del Tratamiento , Tropomiosina/genética , Adulto JovenRESUMEN
OBJECTIVE: Early diagnosis of ankylosing spondylitis (AS) remains challenging because of the high prevalence of chronic back pain in patients initially treated by nonrheumatology health care providers (HCPs). We assessed the patient pathway to rheumatology referral, including HCP recognition of inflammatory back pain (IBP) and other features suggestive of AS, diagnostic workup, treatment, and referral to a specialist with the goal of identifying barriers to patient referral to a rheumatologist. METHODS: US HCPs from 10 specialties were invited to participate in a cross-sectional web-based survey on clinical characteristics and diagnostic measures leading to IBP suspicion and the subsequent referral process. Eligible HCPs were actively practicing and had referred a patient with suspected IBP or ocular findings (ophthalmology only) within 12 months. Data were analyzed descriptively. RESULTS: Of 1690 HCPs, 61% identified morning stiffness lasting more than 30 minutes, 29% sleep disturbance due to back pain, and 28% pain that improves with activity as features suggestive of IBP. Nearly two-thirds of primary care HCPs reported that they were the first HCPs consulted by patients with suspected IBP. Among HCPs ordering diagnostic blood work, approximately 90% selected antinuclear antibody and rheumatoid factor, whereas 76% selected human leukocyte antigen B27. Almost 40% would treat patients with suspected IBP themselves. HCPs cited lack of adequate specialists nearby (35.1%), insurance restrictions (47.1%), and long wait time (77.0%) as barriers to early referral. CONCLUSION: Most HCPs had difficulty identifying features suggestive of IBP and indicated insurance restrictions and long wait times as barriers to early referral of patients with potential AS.
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BACKGROUND AND OBJECTIVE: Patient perspectives regarding treatment experience and satisfaction may be useful for clinicians when making treatment strategies. This US-based study assessed the feasibility of evaluating real-world, patient-reported narratives regarding symptom improvement and treatment satisfaction among patients with psoriatic arthritis treated with secukinumab. METHODS: A cross-sectional, web-based survey collected data on demographics, disease characteristics, symptoms before and after secukinumab use, and treatment satisfaction with secukinumab. RESULTS: Of 2755 patients screened, 200 patients with psoriatic arthritis were eligible and included in the analysis. Their mean age was 36.0 (standard deviation, 10.0) years; 55.5% were male and 75.0% were white. Most (87.5%) were biologic experienced; the primary reason for discontinuation of their previous treatment was lack of effectiveness (28.6%). Most patients (79.9%) reported overall psoriatic arthritis symptom improvement after secukinumab initiation compared with before secukinumab initiation; a similar trend was observed for all individual symptoms evaluated. Approximately half of patients reported improvement within 4 weeks after starting secukinumab treatment, and > 90% reported improvement within 6 months. Most patients (≥ 96%) expressed overall satisfaction with secukinumab regarding symptom improvement, speed of symptom improvement, frequency of administration, method of administration, ease of use, patient support services, and side effects, if any. CONCLUSIONS: Patient-reported perspectives may be feasibly collected to provide insights into treatment experience and satisfaction of secukinumab. Most patients with psoriatic arthritis in our real-world study experienced symptom improvement after initiating secukinumab; > 50% of patients reported symptom improvement within 4 weeks. Additionally, almost all patients reported satisfaction with secukinumab treatment.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Internet , Satisfacción del Paciente , Adulto , Estudios Transversales , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Encuestas y CuestionariosRESUMEN
PURPOSE: This real-world study evaluated the feasibility of assessing patient-reported symptom improvement and treatment satisfaction using a web-based survey among patients with ankylosing spondylitis (AS) treated with secukinumab. METHODS: This cross-sectional, web-based survey collected data on demographics, symptoms, treatment history, and treatment satisfaction from US patients with AS who were receiving secukinumab at survey participation. Patients reported AS symptoms experienced before and after secukinumab initiation, time to symptom improvement, and satisfaction with secukinumab treatment. RESULTS: Of 2755 patients screened, 200 with AS were included in the analysis. The mean (SD) age of patients was 34.4 (10.6) years; 86.5% were biologic experienced. Most (74.0%) reported overall improvement ("a little," "moderately," or "much better") in AS symptoms since secukinumab initiation compared with before secukinumab initiation; a similar trend was observed for all the individual symptoms analyzed (pain disrupting sleep, fatigue, morning stiffness, pain and stiffness in lower back or neck, sore areas other than joints, and ankle or heel pain [indicating enthesitis]). Approximately 41.9% of patients reported overall symptom improvement within 4 weeks of secukinumab treatment. Most expressed overall satisfaction ("very," "mostly," or "somewhat satisfied") with secukinumab regarding symptom improvement (99.0%), speed of symptom improvement (97.0%), frequency and method of administration (96.0% and 91.5%, respectively), ease of use (93.5%), patient support services (97.0%), and side effects, if any (93.0%). CONCLUSION: Most patients reported overall symptom improvement and satisfaction with treatment. Our study indicates that patient-reported perspectives may be feasibly collected using a web-based survey to provide insights into treatment experience and satisfaction.
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BACKGROUND: Hepatotoxic reactions are an important identified risk listed in the agomelatine risk management plan. This post-authorisation safety study evaluated the effectiveness of additional risk-minimisation measures (aRMMs) for agomelatine. OBJECTIVE: The objective of this study was to evaluate, among physicians prescribing agomelatine and their patients, liver function monitoring adherence, compliance with contraindications and patients' reasons for non-compliance with liver monitoring. METHODS: A non-interventional cohort study was conducted among adults initiating agomelatine in routine clinical practice in Denmark, France, Germany and Spain through a retrospective medical record abstraction (MRA) before and after implementation of aRMMs and a cross-sectional patient survey. RESULTS: Fifty-four sites contributed data on 437 and 404 patients in the before- and after-RMM periods, and 237 patients completed the survey. No patient had cirrhosis in either study period; 98.2% of patients in the before- and 98.0% in the after-RMM period had no active liver disease reported at initiation or during treatment. Compliance to contraindicated medications was > 99% in both periods. The adherence to the liver-monitoring regimen was similar in both periods (15.1% before RMM and 16.3% after RMM). In the after-RMM period, 25.2% of patients had a liver test before or at treatment initiation; 61.5% had a liver test during treatment. Among patients surveyed who did not have a blood test before treatment initiation or during treatment, the most frequently cited reason was a test ordered but not yet performed. CONCLUSIONS: The overall adherence to liver-monitoring recommendations remained weakly influenced by aRMMs. However, patients treated with agomelatine are in compliance with relevant contraindications.
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Acetamidas/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Utilización de Medicamentos/estadística & datos numéricos , Hipnóticos y Sedantes/uso terapéutico , Acetamidas/efectos adversos , Anciano , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Europa (Continente) , Femenino , Humanos , Hipnóticos y Sedantes/efectos adversos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Gestión de Riesgos , Resultado del TratamientoRESUMEN
OBJECTIVES: New adjuvant treatments are being developed for patients with resected non-small cell lung cancer (NSCLC). Due to scarcity of real-world data available for treatment costs and resource utilization, health technology and cost-effectiveness assessments can be limited. We estimated the burden and cost-of-illness associated with completely resected stage IB-IIIA NSCLC in France, Germany and the United Kingdom (UK). MATERIALS AND METHODS: Eligible patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC between August 2009 and July 2012. Patients (living or deceased) were enrolled at clinical sites by a systematic sampling method. Data were obtained from medical records and patient surveys. Direct, indirect and patient out-of-pocket expenses were estimated by multiplying resource use by country-specific unit costs. National annual costs were estimated based on disease prevalence data available from published sources. RESULTS: 39 centers provided data from 831 patients of whom patient surveys were evaluable in 306 patients. Median follow-up was 26 months. The mean total direct costs per patient during follow-up were: 19,057 (France), 14,185 (Germany), and 8377 (UK). The largest cost drivers were associated with therapies received (12,375 France; 3694 UK), and hospitalization/emergency costs (7706 Germany). Monthly direct costs per patient were the highest during the distant metastasis/terminal illness phase in France (15,562) and Germany (6047) and during the adjuvant treatment period in the UK (2790). Estimated mean total indirect costs per patient were: 696 (France), 2476 (Germany), and 1414 (UK). Estimates for the annual national direct cost were 478.4 million (France), 574.6 million (Germany) and 325.8 million (UK). CONCLUSION: To our knowledge, this is the first comprehensive study describing the burden of illness for patients with completely resected stage IB-IIIA NSCLC. The economic burden was substantial in all three countries. Treatment of NSCLC is associated with large annual national costs, mainly incurred during disease progression.
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Carcinoma de Pulmón de Células no Pequeñas/economía , Costo de Enfermedad , Neoplasias Pulmonares/economía , Femenino , Estudios de Seguimiento , Francia , Alemania , Costos de la Atención en Salud , Humanos , Masculino , Estadificación de Neoplasias , Calidad de Vida , Estudios Retrospectivos , Reino UnidoRESUMEN
OBJECTIVES: To inform health-technology assessments of new adjuvant treatments, we describe treatment patterns in patients with complete resection of stage IB-IIIA non-small cell lung cancer (NSCLC) in France, Germany, and the United Kingdom (UK). MATERIALS AND METHODS: Data were collected via medical record abstraction. Patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC, diagnosed between 01 January 2009 and 31 December 2011. Median follow-up was 26 months. Adjuvant treatment patterns and clinical outcomes were summarized descriptively. RESULTS: Among the 831 patients studied, 239 (29%) had stage IB disease, 179 (22%) had stage IIA disease, 165 (20%) had stage IIB disease, and 248 (30%) had stage IIIA disease. Adjuvant systemic therapy was received by 402 patients (48.4%), (France, 61.8%; Germany, 51.9%; UK, 33.4%). Use of adjuvant therapy increased with increasing stage of disease. Cisplatin/vinorelbine and carboplatin/vinorelbine were the most frequently prescribed adjuvant regimens. Median disease-free survival was 48.0 months (95% confidence interval [CI] 42.3-not estimable); the 25th percentile was 13.2 months (95% CI, 11.0-15.3). 204 patients (24%) died during the follow-up period. The median overall survival was not reached, the 25th percentile was 31.2 months (95% CI 26.8-36.0 months). 272 patients (33%) had disease recurrence during the follow-up period. For 86 of those patients, the first recurrence was local or regional with no distant metastasis and 14 had further progression to metastatic disease during the follow-up time. For the other 186 patients, the first recurrence involved distant metastases. A total of 200 patients had metastatic disease at any time during study follow-up. CONCLUSIONS: Less than half the patients with stage IB-IIIA NSCLC in this observational study received adjuvant systemic therapy. A high rate of first recurrence with distant metastatic disease was observed, emphasising the need for more effective systemic adjuvant therapies in this population.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioterapia Adyuvante , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/uso terapéutico , Costo de Enfermedad , Femenino , Estudios de Seguimiento , Francia , Alemania , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía , Análisis de Supervivencia , Resultado del Tratamiento , Reino Unido , Vinorelbina/uso terapéuticoRESUMEN
OBJECTIVE: The objective of this study was to compare occupational status and health care resource use between treatment groups in clinical trials 3012 (PP3M versus placebo) and 3011 (PP3M versus PP1M). METHODS: Occupational status was assessed at each study visit. Logistic regressions modeled the probability of hospitalization during the double-blind phase. RESULTS: At the start of each study, a low percentage of patients were full-time employed or gainfully self-employed (approximately 10% in trial 3012 and 11%-13% in trial 3011). Improvement from baseline in occupational status was slightly higher in the PP3M group than in placebo or PP1M groups. The odds of a hospitalization for psychiatric and social reasons during 1 year was 7.74 (95% CI, 2.39-25.05; p < .001) for a patient on placebo compared with the odds of hospitalization during 1 year for a patient on PP3M. No statistically significant difference was observed between PP3M and PP1M (odds ratio, 1.16; 95% CI, 0.70-1.93). Very similar results were observed for hospitalizations due to psychiatric reasons only, within each trial. CONCLUSIONS: In both trials, most patients were unemployed and not seeking work or were retired at open-label baseline, and only a small number of patients changed their occupational status during the trials. In trial 3012, subjects who received placebo had significantly higher odds of hospitalization for either psychiatric and social reasons or for psychiatric reasons alone compared with subjects who received PP3M. In contrast, in trial 3011, the odds of hospitalizations were not significantly different between PP3M and PP1M.
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Antipsicóticos/uso terapéutico , Empleo , Palmitato de Paliperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Método Doble Ciego , Hospitalización , HumanosRESUMEN
BACKGROUND: Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials. METHODS: A systematic literature review identified relevant trials. Separate analyses were conducted for each palbociclib combination using a Bayesian approach. Treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). RESULTS: Sixty-five unique studies met inclusion criteria. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all comparators in treatment-naïve patients (hazard ratios [HRs] ranged from 0.41 to 0.58). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and, in previously treated patients, yielded significantly longer PFS than most comparators (HRs ranged from 0.26 to 0.46); the exception was everolimus plus exemestane, with similar PFS (HR, 1.04; 95% credible interval [CrI], 0.58-1.76). Palbociclib plus fulvestrant was associated with significantly lower odds of discontinuation due to adverse events than everolimus plus exemestane (odds ratio, 0.14; 95% CrI, 0.05-0.39). CONCLUSIONS: The results suggest that the two palbociclib combinations yielded significantly greater PFS than endocrine therapy in treatment-naïve and previously treated patients with advanced/metastatic breast cancer. Palbociclib plus fulvestrant was associated with significantly less toxicity than everolimus plus exemestane.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Androstadienos/administración & dosificación , Teorema de Bayes , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Estradiol/administración & dosificación , Estradiol/análogos & derivados , Everolimus/administración & dosificación , Femenino , Fulvestrant , Humanos , Letrozol , Metaanálisis en Red , Nitrilos/administración & dosificación , Piperazinas/administración & dosificación , Piridinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Triazoles/administración & dosificaciónRESUMEN
PURPOSE: To evaluate the impact of a state-of-the-art Quit and Win contest on tobacco quit rates at 3, 6, and 12 months after the 30-day quit period. DESIGN: Quasi-experimental with a volunteer sample of 494 Quit and Win contest registrants (treatment group) and 512 randomly selected tobacco users not exposed to the promotional media campaign (control group). Intervention included a 30-day quit period to be eligible for large cash prizes; provider advice via weekly mailings; online and telephone quit assistance; media campaign; and community support. SETTING: Community-based intervention in Kentucky. SUBJECTS: A total of 1006 adult tobacco users. MEASURES: Quit rates were measured using 7-day point prevalence for tobacco use. Urine cotinine measurements confirmed self-reported quitting. RESULTS: Treatment group participants were significantly more likely than controls to experience quitting during the 1-year follow-up, as determined by both self-report and urine confirmation. After adjusting for baseline differences in demographics, tobacco use, and stage of change, those in the treatment group had 2.6 times the odds of reporting quitting in the postintervention period and 5.3 times the odds of experiencing quitting confirmed by urine cotinine, relative to controls. Women, minorities, and low-income tobacco users had equal odds of quitting as men, whites, and those with higher incomes. CONCLUSIONS: That the contest was minimally intensive and yielded a relatively high, quit rate demonstrates the potential effectiveness of the intervention.
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Promoción de la Salud/métodos , Cese del Hábito de Fumar , Adulto , Femenino , Humanos , Kentucky , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Determine whether reimbursement restrictions recommended by the National Institute for Health and Clinical Excellence (NICE) have impacted the United Kingdom (UK) National Health Service (NHS) budget. METHODS: Data were abstracted from NICE guidance documents and costing statements through March 2011. Estimated maximum and adjusted potential budget impact (PBI) on the NHS was derived using estimates of the UK marketing-approved population and the annual cost for the new drug. Descriptive and logistic analyses were used to estimate the correlation between the degree of restrictions on reimbursement recommended by NICE for each new drug indication and the PBI controlling for clinical effectiveness and cost-effectiveness. RESULTS: PBI was significantly correlated with the degree of reimbursement restrictions. In descriptive analysis, the adjusted PBI for drugs that were recommended without restrictions was £20.3 million (SD = 22.2) compared with £49.8 million (SD = 90.8) for those recommended with restrictions and £71.1 million (SE = 99.9) for those not recommended. In logistic analysis, the odds ratio for less restrictive reimbursement was 0.848 (95% CI, 0.762-0.945) for each £20 million increase in the adjusted PBI. Results were similar using the maximum PBI. CONCLUSIONS: After controlling for clinical effectiveness and cost-effectiveness, the degree of reimbursement restriction recommended by NICE remains significantly correlated with the PBI, despite that fact that the NICE decision process does not consider budget impact. This correlation might be due to NICE consideration of effectiveness and cost-effectiveness for subgroups of the approved population.
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Costos de los Medicamentos/estadística & datos numéricos , Medicamentos bajo Prescripción/economía , Mecanismo de Reembolso/organización & administración , Medicina Estatal/organización & administración , Presupuestos/organización & administración , Análisis Costo-Beneficio , Humanos , Medicamentos bajo Prescripción/uso terapéutico , Mecanismo de Reembolso/economía , Medicina Estatal/economía , Resultado del TratamientoRESUMEN
PURPOSE: The cost-effectiveness of voriconazole versus fluconazole prophylaxis against fungal infections in hematopoietic cell transplant (HCT) recipients is investigated. METHODS: A decision-analytic model was developed to estimate the drug costs associated with planned or supplemental prophylaxis and empirical therapy and the costs of treating suspected or documented invasive fungal infections (IFIs) in HCT recipients. Published clinical trial data on 599 patients who received 100-180 days of prophylactic therapy with voriconazole or fluconazole were used to model specified IFI-prevention and mortality outcomes; 6-month, 12-month, and lifetime incremental cost-effectiveness ratios (ICERs) were estimated, with a bootstrap analysis performed to reffect the uncertainty of the clinical trial data. RESULTS: Estimated mean total prophylaxis and IFI-related costs associated with voriconazole versus fluconazole prophylaxis over 12 months were higher in the entire study population and among patients receiving HCT for diagnoses other than acute myeloid leukemia (AML) but were not significantly different for patients with AML. The cost per IFI avoided ($66,919) and the cost per life-year gained ($5,453) were lower among patients with AML who received voriconazole relative to the full study population. ICERs were more favorable for voriconazole over a 6-month time frame and when modeling was conducted using generic price data. Assuming a threshold value of $50,000 for one year of life gained, the calculated probability of voriconazole being cost-effective was 33% for the full study population and 85% for the AML subgroup. CONCLUSION: The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML.
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Antifúngicos/economía , Técnicas de Apoyo para la Decisión , Fluconazol/economía , Trasplante de Células Madre Hematopoyéticas/economía , Micosis/economía , Pirimidinas/economía , Triazoles/economía , Antifúngicos/uso terapéutico , Estudios de Casos y Controles , Estudios de Cohortes , Análisis Costo-Beneficio , Método Doble Ciego , Fluconazol/uso terapéutico , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Micosis/tratamiento farmacológico , Micosis/epidemiología , Pirimidinas/uso terapéutico , Trasplante Homólogo , Triazoles/uso terapéutico , VoriconazolRESUMEN
BACKGROUND: In a two-group quasi-experimental study, we evaluated the impact of a quit and win contest on quitting among low-income tobacco users and identified contest elements used by successful quitters. Low-income tobacco users have been largely untouched by tobacco cessation approaches. METHODS: A volunteer sample of 248 low-income tobacco users were recruited from quit and win contest registrants (treatment group). A random sample of 290 low-income tobacco users who had not entered the contest were recruited using random digit dialing (control group). Telephone interviews were conducted with both groups at baseline, 3, 6, and 12 months. Seven-day point prevalence measured self-reported quitting and urine cotinine assessed confirmed quitting. RESULTS: On average, quit and win study participants were 3.5 times more likely than controls to self-report quitting and 12.8 times more likely to demonstrate confirmed quitting after controlling for baseline differences in stage of change, age, education, and marital status. The use of specific contest elements was not related to successful quitting. CONCLUSIONS: The overall quit rates in the treatment group were higher than those in the control group. The results are promising given that low-income tobacco users are generally less likely to succeed in quitting.