Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 575
Filtrar
3.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470632

RESUMO

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Drogas em Investigação/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Saúde Global/tendências , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Acinetobacter baumannii/fisiologia , Aminoglicosídeos/síntese química , Aminoglicosídeos/economia , Aminoglicosídeos/uso terapêutico , Antibacterianos/síntese química , Antibacterianos/economia , Aprovação de Drogas/organização & administração , Drogas em Investigação/síntese química , Drogas em Investigação/economia , Enterobacteriaceae/patogenicidade , Enterobacteriaceae/fisiologia , Fluoroquinolonas/síntese química , Fluoroquinolonas/economia , Fluoroquinolonas/uso terapêutico , Saúde Global/economia , Glicopeptídeos/síntese química , Glicopeptídeos/economia , Glicopeptídeos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Negativas/fisiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Humanos , Macrolídeos/síntese química , Macrolídeos/economia , Macrolídeos/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , beta-Lactamas/síntese química , beta-Lactamas/economia , beta-Lactamas/uso terapêutico
10.
N Z Med J ; 132(1490): 36-41, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30789887

RESUMO

AIMS: Teriflunomide, used globally to treat multiple sclerosis (MS) and widely subsidised for this indication including in Australia and New Zealand, is the main metabolite of leflunomide, an older immune-modulating drug. Leflunomide therefore represents a potential alternative therapy for MS. Teriflunomide is about 50-500 times more expensive than leflunomide, depending on prices in each jurisdiction. I wished to study how this situation arose. METHODS: Web search to obtain the publicly available minutes of eight international regulatory bodies that have approved teriflunomide for the governments of the US, Canada, Europe, England, Scotland, Australia (TGA and PBS) and New Zealand, and examination of the processes and minuted discussions concerning the metabolic, efficacy, toxicity and cost relationship between teriflunomide and leflunomide. RESULTS: The relationship between the two drugs and their relative efficacy or toxicity in MS was considered by three of eight agencies (Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Canadian Agency for Drugs and Technology in Health (CADTH)). The remaining agencies accepted teriflunomide applications at face value, assessed cost-effectiveness against contemporaneous drugs used for treating MS, and did not discuss the potential role of leflunomide as a therapy for MS. No agency minuted the implications of the cost difference. CONCLUSIONS: Efficacy for leflunomide in MS is likely but unproven. The sponsor presented a case for teriflunomide that was within the established procedures for drug agencies in establishing cost-effectiveness, and agencies did not stray from their normal procedures. As a result, an opportunity to decrease the cost of treating MS has been missed. Though off-label use of leflunomide is possible, this is unlikely without a publicly-funded trial to demonstrate non-inferiority with regard to efficacy and safety.


Assuntos
Crotonatos , Aprovação de Drogas , Leflunomida , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Toluidinas , Austrália , Análise Custo-Benefício , Crotonatos/economia , Crotonatos/farmacologia , Aprovação de Drogas/métodos , Aprovação de Drogas/organização & administração , Custos de Medicamentos , Financiamento Governamental , Humanos , Imunossupressores/economia , Imunossupressores/farmacologia , Leflunomida/economia , Leflunomida/farmacologia , Nova Zelândia , Toluidinas/economia , Toluidinas/farmacologia
11.
Health Qual Life Outcomes ; 17(1): 4, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616654

RESUMO

BACKGROUND: Patient reported outcome measures (PROMs) and minimal clinically important differences (MCIDs) are included in Canada's Common Drug Review (CDR) process to approve new drugs. Often, the measures report on the health-related quality of life (HRQoL), but can also describe the symptoms, efficacy and harms important to patients. They can be generic or population/condition specific, validated or not. We examined the frequency, availability and accessibility of validated, specific PROMs and MCIDs reported in the CDR reports. METHODS: We searched the Canadian Agency for Drugs and Technologies in Health (CADTH) on-line database for completed Common Drug Review, Clinical Review Reports (CDR-CRR) between November 2013 and February 2017. Two independent reviewers examined the reports and references for PROMs and MCIDs. Both reviewers separately categorized the PROMs and MICDs according to purpose, validation, availability and funding received. Discrepancies were rectified by consensus with a third investigator. RESULTS: One-hundred and five unique PROMs were extracted from 39 CDR-CRR, 57% with a HRQoL component. 91/105 (87%) referenced a validation study and 62/105 (59%) referenced a validation study in the study population of interest. Fifty-seven MCID references were extracted from 39 CDR-CRR. 34/57 (60%) were specific to the study population of interest, and 36% had a HRQoL component. 50% of PROM and 53% of MCID references were publicly available. CONCLUSIONS: PROMs and MCIDs referenced in CDR-CRR show similar trends. The majority are validated, but not necessarily in the study population of interest. Continued critical examination is required to evaluate new drugs specific to the population of interest.


Assuntos
Aprovação de Drogas/organização & administração , Diferença Mínima Clinicamente Importante , Medidas de Resultados Relatados pelo Paciente , Canadá , Humanos , Qualidade de Vida
12.
J Clin Epidemiol ; 105: 50-59, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30236484

RESUMO

OBJECTIVE: To identify and assess the methods for estimating comparative clinical effectiveness for novel pharmaceutical products licensed on the basis of nonrandomized controlled trial (non-RCT) data and to evaluate the corresponding National Institute for Health and Care Excellence (NICE) recommendations. METHODS: Our identification strategy was twofold. First, we reviewed all NICE appraisals between 2010 and 2016 and identified technologies where comparative clinical effectiveness estimates were calculated using non-RCT data. Second, we checked if NICE appraisals completed from 2000 to 2010 had included pharmaceuticals that were granted European Medicines Agency marketing authorization without RCT data between 1999 and 2014. Information was extracted on the method used to establish comparative clinical effectiveness as well as the corresponding NICE recommendations. We also collected information on the rationale for utilizing non-RCT data in NICE appraisals. RESULTS: Of 489 individual pharmaceutical technologies assessed by NICE, 22 (4%) used non-RCT data to estimate comparative clinical effectiveness. Methods for establishing external controls in such studies varied: 13 (59%) used published trials, 6 (27%) used observational data, 2 (9%) used expert opinion, and 1 (5%) used a responder vs nonresponder analysis. Only 5 (23%) used a regression model to adjust for covariates. We did not observe a notable difference in the proportion of pharmaceutical technologies that received a positive recommendation from NICE whether the decision was based on RCT or non-RCT data (83% vs 86%). CONCLUSIONS: To date, a small number of appraisals by NICE based on non-RCT data did not result in substantially different treatment decisions. The majority of the technologies appraised on the basis of non-RCT data either received a positive recommendation or a positive recommendation with restrictions. The methods used to calculate comparative clinical effectiveness estimates varied, highlighting the need to establish clear guidance.


Assuntos
Aprovação de Drogas , Prática Clínica Baseada em Evidências/normas , Medicina Estatal , Tecnologia Farmacêutica/normas , Pesquisa Comparativa da Efetividade , Aprovação de Drogas/métodos , Aprovação de Drogas/organização & administração , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Vigilância de Produtos Comercializados/estatística & dados numéricos , Reino Unido
13.
Int J Health Serv ; 49(2): 294-305, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30587064

RESUMO

Health Canada has developed its Notice of Compliance with conditions (NOC/c) policy to get promising new drugs for serious diseases to market faster than would be possible through its standard approval process. Companies can receive an NOC/c for a new drug or a new indication based on incomplete evidence in return for agreeing to conduct post-market studies. This paper investigates the additional therapeutic gain from drugs approved under this policy, the percent of drugs that have fulfilled their conditions, and the length of time for fulfillment. From the inception of the policy in 1998 to the end of 2017, 89 new drugs and new indications for existing drugs received an NOC/c. Therapeutic evaluations were available for 78 of the drugs, and 54 offered only minimal or no gains over existing products. Fifty NOC/c were fulfilled, 31 were not fulfilled, and 8 were withdrawn. The median time to fulfillment was 1,040 days. Twelve NOC/c took more than 5 years to fulfill their conditions. The unfulfilled NOC/c had been issued for a median of 1,161 days, and 10 had been issued more than 5 years. The value of the NOC/c policy to patients is uncertain.


Assuntos
Aprovação de Drogas , Canadá , Aprovação de Drogas/métodos , Aprovação de Drogas/organização & administração , Aprovação de Drogas/estatística & dados numéricos , Órgãos Governamentais/organização & administração , Política de Saúde , Humanos , Estudos Retrospectivos , Fatores de Tempo
14.
J Natl Compr Canc Netw ; 16(12): 1460-1466, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30545993

RESUMO

Background: FDA approvals do not consider cost, but they set the tone for regulatory approvals worldwide, including in countries with universal healthcare where cost-effectiveness, utility, and adoption feasibility are considered rigorously. Methods: Data from the pan-Canadian Oncology Drug Review (pCODR), a national drug review system that makes evidence-based funding recommendations to Canada's provinces and territories, were collected. Our objectives were to assess (1) temporal trends in cost and efficacy of drugs reviewed, (2) correlations among magnitude of benefits, cost, and pCODR decisions, and (3) predictors of approvals. Results: A total of 60 drugs for 91 indications were reviewed by pCODR from January 2012 to January 2018. Of the 91 reviews (approved previously by FDA), 18 received negative recommendations on the grounds of inadequate clinical benefits; 87% (64/73) of those approved were conditional on improvement in cost. Surrogate outcomes were used to support approvals in 83% of the reviews, which were not correlated with overall survival (rSpearman = +0.16; P=.24). Median cost/quality-adjusted life years (QALY) increased by 36% per annum (quantile regression, P=.0029), although benefits in overall and progression-free survival were stable (P=.21 and .65, respectively). Median-based incremental cost-effectiveness ratio (ICER) of new drugs was $186,403 CAD (range, $7,200 to $2.1 million). Higher ICER was a strong predictor of a negative pCODR recommendation (P<.01). Conclusions: A substantial number of cancer drugs that are FDA approved for public use do not meet Canadian standards for efficacy. Cost of cancer drugs increases by a third annually in Canada, but the benefits-measured mostly with surrogates that did not correlate with survival-are stable. With finite resources to share among multiple societal priorities, such as education and preventive health, cancer drug cost may be unsustainable despite price regulation.


Assuntos
Antineoplásicos/economia , Análise Custo-Benefício/métodos , Aprovação de Drogas/organização & administração , Neoplasias/tratamento farmacológico , Cobertura Universal do Seguro de Saúde/organização & administração , Antineoplásicos/uso terapêutico , Canadá , Aprovação de Drogas/métodos , Custos de Medicamentos/legislação & jurisprudência , Humanos , Neoplasias/economia , Neoplasias/mortalidade , Intervalo Livre de Progressão , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos , United States Food and Drug Administration/organização & administração , Cobertura Universal do Seguro de Saúde/economia
15.
Rev. psiquiatr. salud ment. (Barc., Ed. impr.) ; 11(4): 208-215, oct.-dic. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-176754

RESUMO

Introduction: Trazodone was authorized for the treatment of depression in the 1970s. Several additional therapeutic uses have been proposed due to its heterogeneous mechanism. This study aims to determine the use of trazodone in the elderly in Spain. Methods: A nationwide, longitudinal and descriptive analysis was conducted using data from patients aged >65 years with a first prescription of trazodone during the period 2002-2011. Information on dose, comorbidities and relevant co-medication was gathered from the Spanish Primary Care database BIFAP. Incidence rates of trazodone use per 10,000 person-years were calculated by sex and age. Results: A total of 11,766 patients receiving a first prescription of trazodone were included. The incidence rate of trazodone use was 47.2 (95% CI: 46.33-48.04) per 10,000 person-years. An increasing trend in the use of trazodone was observed (5-fold increase in 2011 as compared to 2002). The most common therapeutic indications were: depression (21.41%), Alzheimer/dementia (20.36%), sleep disorders (16.22%), and anxiety disorder (8.91%). The median dose was 100mg/day. The use of trazodone concomitantly with interacting medicines was frequent: anti-hypertensives (53.60%), and CNS depressors (59.32%). Conclusions: Trazodone use is increasing in elderly patients, and a high proportion of use in non-approved indications was observed. Trazodone is not being used at high doses, but interacting medicines were frequent, and it may pose additional risks for elderly patients


Introducción: La trazodona se autorizó para el tratamiento de la depresión en los años 70, y se han propuesto otros usos por su mecanismo de acción heterogéneo. Este estudio tiene como objetivo caracterizar la utilización de trazodona en ancianos en España. Métodos: Se llevó a cabo un análisis longitudinal en pacientes>65 años con una primera prescripción de trazodona durante el periodo 2002-2011. Se obtuvo información a partir de datos de BIFAP sobre la dosis, indicaciones, comorbilidades y medicación concomitante. Se calcularon las tasas de uso por 10.000 personas-año por grupos de edad (66-75; >75) y sexo. Se llevó a cabo un análisis descriptivo de las principales indicaciones y la comedicación. Resultados: Se identificaron 11.766 pacientes con una primera prescripción de trazodona en el periodo de estudio. La tasa de incidencia de utilización fue de 47,2 (IC95%: 46,33-48,04) por 10.000 personas-año. El uso se quintuplicó en 2011 respecto a 2002. Las indicaciones terapéuticas más frecuentes fueron: depresión (21,41%), enfermedad de Alzheimer/demencia (20,36%), trastornos del sueño (16,22%), trastorno de ansiedad (8,91%). La mediana de la dosis fue 100mg/día. El uso de medicación concomitante que podría interaccionar fue frecuente: antihipertensivos (53,60%) y depresores del sistema nervioso central (59,32%). Conclusiones: La utilización de trazodona ha aumentado en pacientes ancianos y se ha registrado una gran proporción de uso en indicaciones no autorizadas. El empleo de trazodona a dosis altas es infrecuente, sin embargo una gran proporción de pacientes estaban siendo tratados con medicamentos que interaccionan con trazodona y que podrían aumentar el riesgo en ancianos


Assuntos
Humanos , Masculino , Feminino , Idoso , Trazodona/uso terapêutico , Aprovação de Drogas/organização & administração , Ensaios de Uso Compassivo/tendências , Estudos Longitudinais , Revisão de Uso de Medicamentos/organização & administração , Interações de Medicamentos , Fatores de Risco
17.
Tex Med ; 114(9): 42-45, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30240485

RESUMO

Vaccines in development for diseases in Texas and beyond often sit around untested.


Assuntos
Licenciamento , Vacinas/provisão & distribução , Vacinas/normas , Aprovação de Drogas/organização & administração , Humanos , Texas , Estados Unidos , United States Food and Drug Administration
18.
BMJ Open ; 8(8): e023605, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-30166310

RESUMO

OBJECTIVES: This study examines the use of expedited approval pathways by Health Canada over the period 1995 to 2016 inclusive and the relationship between the use of these pathways and the therapeutic gain offered by new products. DESIGN: Cross-sectional study. DATA SOURCES: Therapeutic Products Directorate, Biologics and Genetic Therapies Directorate, Notice of Compliance database, Notice of Compliance with conditions web site, Patented Medicine Prices Review Board, La revue Prescrire, WHO Anatomical Therapeutic Chemical classification system. PRIMARY AND SECONDARY OUTCOMES: Percent of new drugs evaluated by Health Canada that went through an expedited pathway between 1995 and 2016 inclusive. Kappa values comparing the review status with assessments of therapeutic value for individual drugs. RESULTS: Of 623 drugs approved by Health Canada between 1995 and 2016, 438 (70.3%) drugs went through the standard pathway and 185 (29.7%) an expedited pathway. Therapeutic evaluations were available for 509 drugs. Health Canada used an expedited approval pathway for 159 of the 509 drugs, whereas only 55 were judged to be therapeutically innovative. Forty-two of the 55 therapeutically innovative drugs received an expedited review and 13 received a standard review. The Kappa value for the entire period for all 509 drugs was 0.276 (95% CI 0.194 to 0.359) indicating 'fair' agreement between Health Canada's use of expedited pathways and independent evaluations of therapeutic innovation. CONCLUSION: Health Canada's use of expedited approvals was stable over the entire time period. It was unable to reliably predict which drugs will offer major therapeutic gains. The findings in this study should provoke a discussion about whether Health Canada should continue to use these pathways and if so how their use can be improved.


Assuntos
Aprovação de Drogas/organização & administração , Canadá , Estudos Transversais , Difusão de Inovações , Aprovação de Drogas/estatística & dados numéricos , Humanos , Fatores de Tempo
19.
Pediatr Dermatol ; 35(5): 688-689, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30066378

RESUMO

Although systemic etanercept was approved in 2004 for adults, the Food and Drug Administration (FDA) denied approval for use in children with psoriasis in 2008. Revision of the FDA's risk-benefit assessment in response to understanding of disease burden, unmet medical need, and the effect of off-label use in children with psoriasis led to the 2016 approval as the first systemic biologic product for the treatment of children aged 4-17 with moderate to severe psoriasis. This article delineates the thinking that led to this reconsideration. The underlying thinking paved the way to inform current pediatric drug development as the FDA continues to bring needed medical products to children.


Assuntos
Aprovação de Drogas/organização & administração , Etanercepte/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Etanercepte/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Uso Off-Label , Estados Unidos , United States Food and Drug Administration
20.
Pediatr Rheumatol Online J ; 16(1): 45, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29996857

RESUMO

IMPORTANCE: Specialized research networks are essential to achieve drug approvals for rare pediatric diseases. Such networks help realize the potential of global legislation enacted upon the recognition that most children are treated with drugs whose most beneficial dose and regimen have not been established in pediatric patients. The Pediatric Rheumatology Collaborative Study Group (PRCSG) is a North American clinical trials network that is specialized in the performance of clinical trials of new therapies for pediatric populations with rheumatic diseases. This review provides an overview of the strategies employed by this research network to achieve drug and biologic approvals for children with pediatric rheumatic diseases, particularly juvenile idiopathic arthritis. OBSERVATIONS: Clinical trial conduct in rare pediatric diseases has required global recruitment. Supported or led by the PRCSG, highly responsive, validated, composite measures have been established to assess drug efficacy. For pediatric orphan diseases with high disease burdens, specialized investigative sites and study designs are needed to complete adequately powered trials at the high standard necessary to enable drug labeling by regulatory agencies. Novel trial designs have been utilized for more efficient testing of innovative drug candidates. All these have been developed or co-developed by the PRCSG research network. CONCLUSIONS AND RELEVANCE: Specialized research networks in pediatric rheumatology, such as the PRCSG, have changed the landscape of available therapies and improved overall disease outcomes for children with pediatric rheumatic diseases.


Assuntos
Antirreumáticos/uso terapêutico , Pesquisa Biomédica/organização & administração , Doenças Reumáticas/tratamento farmacológico , Reumatologia/organização & administração , Criança , Ensaios Clínicos como Assunto/métodos , Aprovação de Drogas/métodos , Aprovação de Drogas/organização & administração , Humanos , Projetos de Pesquisa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA