ABSTRACT
Las enfermedades raras son aquellas que tienen baja prevalencia y que, por lo tanto, el desarrollo de medicamentos para tratarlas no es rentable para las empresas farmacéuticas debido a la baja demanda. A pesar de que ya se cuenta con diferentes políticas públicas alrededor del mundo para incentivar a las industrias farmacéuticas a investigar estos medicamentos, conocidos como medicamentos huérfanos, su desarrollo conlleva muchas dificultades en las evaluaciones clínicas y el precio final para el público es muy elevado. Si bien en años recientes se ha planteado el uso de tecnología de impresión en 3D para producir estos medicamentos o incluso recurrir a otros medicamentos previamente aprobados para tratar enfermedades raras, existe un historial de mal uso de las legislaciones por parte de las empresas con el fin de generar beneficios comerciales, por lo que estas políticas deben reforzarse para que cumplan su propósito; ayudar a una población muy vulnerable. El objetivo del presente texto es exponer los resultados de una revisión documental sobre el panorama científico y sociopolítico en el que se encuentra el problema de las enfermedades raras y los medicamentos huérfanos, así como las posibles soluciones que se están desplegando para abordarlo. Deriva de un estudio que se desarrolla en el momento actual en la Universidad Autónoma Metropolitana, de Ciudad de México.
The strange illnesses are those that have low prevalence and that, therefore, the development of medications to treat them is not profitable for the pharmaceutical companies due to the drop demands. Although it is already counted with different political public around the world to motivate to the pharmaceutical industries to investigate these medications, well-known as orphan medications, their development bears many difficulties in the clinical evaluations and the final price for the public it is very high. Although in recent years he/she has thought about the use of impression technology in 3D to produce these medications or even to appeal to other medications previously approved to treat strange illnesses, a record of wrong use of the legislations exists on the part of the companies with the purpose of generating commercial benefits, for what these politicians should be reinforced so that they complete its purpose; to help a very vulnerable population. The objective of the present text is to expose the results of a documental revision on the scientific and sociopolitical panorama in which is the problem of the strange illnesses and the orphan medications, as well as the possible solutions that they are spreading to approach it. It derives of a study that is developed in the current moment in the Metropolitan Autonomous University, of Mexico City.
ABSTRACT
INTRODUCTION: Hereditary factor X deficiency is a rare bleeding disorder, with limited treatment options. This paper describes the approach to pre-clinical development and characterization of a high-purity plasma-derived factor X concentrate, to achieve orphan drug marketing authorization for the treatment of hereditary factor X deficiency. METHODS: A chromatographic process was developed, to purify factor X from human plasma for fractionation. The product was characterized using in vitro, in vivo and ex vivo tests for potency, purity, thrombogenicity, immunogenicity, toxicity and stability. RESULTS: The production process complied with good pharmaceutical manufacturing practice. It achieved 6000-fold purification and 100-fold concentration of the factor X protein compared to human plasma. The factor X protein was 94%-96% pure. Other residual plasma proteins were well below levels in plasma, minimizing potential interference in hemostasis after therapeutic administration. Effective virus-reduction during manufacture, and the absence of thrombogenicity, toxicity and immunogenic potential were confirmed, addressing the main safety concerns historically associated with plasma-derived therapeutics. The freeze-dried product remained stable between +2°C and +30°C for at least three years. After reconstitution with water for injections, the factor X activity was maintained for at least 48 h at +18°C to +22°C. CONCLUSION: Targeted pre-clinical development of the first highly-purified concentrate to treat hereditary factor X deficiency is described. Following international guidelines for nonclinical safety testing, particular strategies were adopted for unmodified products derived from human blood plasma. This approach may also be relevant to the development of other ultra-orphan medicinal products.
Subject(s)
Factor X Deficiency , Factor X , Humans , Factor X/therapeutic use , Factor X Deficiency/drug therapy , Factor X Deficiency/complications , Hemorrhage/complications , Plasma , Pharmaceutical PreparationsABSTRACT
There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.
Subject(s)
Orphan Drug Production , Rare Diseases , Humans , Child , Rare Diseases/drug therapy , Pharmaceutical PreparationsABSTRACT
There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.
Subject(s)
Humans , Child , Rare Diseases/drug therapy , Orphan Drug Production , Pharmaceutical PreparationsABSTRACT
Introducción El abordaje terapéutico de las manifestaciones cutáneas de las enfermedades raras es complejo. El objetivo principal de este trabajo consistió en determinar el impacto de la formulación magistral de dispensación hospitalaria en la calidad de vida de los pacientes con genodermatosis. Material y métodos Se diseñó un estudio descriptivo transversal. Se incluyeron pacientes con genodermatosis que recibieron tratamientos tópicos elaborados y dispensados por el Servicio de Farmacia Hospitalaria del Complejo Hospitalario Universitario de Pontevedra. Se recogieron datos demográficos, cuestionarios generales y específicos sobre la calidad de vida, y cuestionarios que evaluaban los tratamientos administrados y la adherencia terapéutica. Resultados Se incluyeron 9 pacientes. Se observó que, tras la terapia con fórmulas magistrales, hubo una reducción estadísticamente significativa del impacto en la calidad de vida de los pacientes. La satisfacción con los productos fue 2,8 sobre 25 (siendo 0 la mejor puntuación). La adherencia terapéutica superó el 89%. Conclusiones La formulación magistral permite el acceso a medicamentos huérfanos y no comercializados para numerosas enfermedades raras. Su impacto en la calidad de vida de los pacientes afectos de estas enfermedades ha sido escasamente estudiado. En la serie de pacientes que se presenta, la elaboración y dispensación hospitalaria de fórmulas magistrales específicas conllevó efectos positivos en su calidad de vida. Este estudio inicial ha derivado en otro trabajo multicéntrico, centrado en las ictiosis, donde previsiblemente aumentará el número de pacientes a incluir y permitirá confirmar nuestros resultados (AU)
Background Cutaneous manifestations are complicated to treat in rare diseases. The main aim of this study was to analyze the impact of compounded drugs prepared by hospital pharmacists on the quality of life of patients with genodermatoses. Material and methods We undertook a cross-sectional study of patients with genodermatoses treated with topical medications compounded and dispensed by the pharmacy at Complejo Hospitalario Universitario in Pontevedra, Spain. We collected demographic data and answers to questionnaires examining generic and disease-specific quality of life, treatment satisfaction, and treatment adherence.Results Nine patients were included. We observed a significant improvement in health-related quality of life following treatment with compounded drugs. Satisfaction with the topical medications was 2.8 on a scale of 0 (greatest satisfaction) to 25. Treatment adherence was 59%. Conclusions Drug compounding facilitates access to orphan drugs that are not available for many rare diseases. Few studies, however, have analyzed impact on quality of life in this setting. In this series of patients with genodermatoses, topical medications compounded and dispensed by a hospital pharmacy improved health-related quality of life. This preliminary study has given rise to a multicenter study of compounding for ichthyosis. We expect that analysis of a larger sample will confirm our findings (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Treatment Adherence and Compliance , Orphan Drug Production , Drugs from the Specialized Component of Pharmaceutical Care , Ichthyosis, Lamellar/drug therapy , Tuberous Sclerosis/drug therapy , Epidermolysis Bullosa/drug therapy , Patient Satisfaction , Cross-Sectional Studies , Quality of LifeABSTRACT
Background Cutaneous manifestations are complicated to treat in rare diseases. The main aim of this study was to analyze the impact of compounded drugs prepared by hospital pharmacists on the quality of life of patients with genodermatoses. Material and methods We undertook a cross-sectional study of patients with genodermatoses treated with topical medications compounded and dispensed by the pharmacy at Complejo Hospitalario Universitario in Pontevedra, Spain. We collected demographic data and answers to questionnaires examining generic and disease-specific quality of life, treatment satisfaction, and treatment adherence.Results Nine patients were included. We observed a significant improvement in health-related quality of life following treatment with compounded drugs. Satisfaction with the topical medications was 2.8 on a scale of 0 (greatest satisfaction) to 25. Treatment adherence was 59%. Conclusions Drug compounding facilitates access to orphan drugs that are not available for many rare diseases. Few studies, however, have analyzed impact on quality of life in this setting. In this series of patients with genodermatoses, topical medications compounded and dispensed by a hospital pharmacy improved health-related quality of life. This preliminary study has given rise to a multicenter study of compounding for ichthyosis. We expect that analysis of a larger sample will confirm our findings (AU)
Introducción El abordaje terapéutico de las manifestaciones cutáneas de las enfermedades raras es complejo. El objetivo principal de este trabajo consistió en determinar el impacto de la formulación magistral de dispensación hospitalaria en la calidad de vida de los pacientes con genodermatosis. Material y métodos Se diseñó un estudio descriptivo transversal. Se incluyeron pacientes con genodermatosis que recibieron tratamientos tópicos elaborados y dispensados por el Servicio de Farmacia Hospitalaria del Complejo Hospitalario Universitario de Pontevedra. Se recogieron datos demográficos, cuestionarios generales y específicos sobre la calidad de vida, y cuestionarios que evaluaban los tratamientos administrados y la adherencia terapéutica. Resultados Se incluyeron 9 pacientes. Se observó que, tras la terapia con fórmulas magistrales, hubo una reducción estadísticamente significativa del impacto en la calidad de vida de los pacientes. La satisfacción con los productos fue 2,8 sobre 25 (siendo 0 la mejor puntuación). La adherencia terapéutica superó el 89%. Conclusiones La formulación magistral permite el acceso a medicamentos huérfanos y no comercializados para numerosas enfermedades raras. Su impacto en la calidad de vida de los pacientes afectos de estas enfermedades ha sido escasamente estudiado. En la serie de pacientes que se presenta, la elaboración y dispensación hospitalaria de fórmulas magistrales específicas conllevó efectos positivos en su calidad de vida. Este estudio inicial ha derivado en otro trabajo multicéntrico, centrado en las ictiosis, donde previsiblemente aumentará el número de pacientes a incluir y permitirá confirmar nuestros resultados (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Treatment Adherence and Compliance , Orphan Drug Production , Drugs from the Specialized Component of Pharmaceutical Care , Ichthyosis, Lamellar/drug therapy , Tuberous Sclerosis/drug therapy , Epidermolysis Bullosa/drug therapy , Patient Satisfaction , Cross-Sectional Studies , Quality of LifeABSTRACT
BACKGROUND: Cutaneous manifestations are complicated to treat in rare diseases. The main aim of this study was to analyze the impact of compounded drugs prepared by hospital pharmacists on the quality of life of patients with genodermatoses. MATERIAL AND METHODS: We undertook a cross-sectional study of patients with genodermatoses treated with topical medications compounded and dispensed by the pharmacy at Complejo Hospitalario Universitario in Pontevedra, Spain. We collected demographic data and answers to questionnaires examining generic and disease-specific quality of life, treatment satisfaction, and treatment adherence. RESULTS: Nine patients were included. We observed a significant improvement in health-related quality of life following treatment with compounded drugs. Satisfaction with the topical medications was 2.8 on a scale of 0 (greatest satisfaction) to 25. Treatment adherence was 59%. CONCLUSIONS: Drug compounding facilitates access to orphan drugs that are not available for many rare diseases. Few studies, however, have analyzed impact on quality of life in this setting. In this series of patients with genodermatoses, topical medications compounded and dispensed by a hospital pharmacy improved health-related quality of life. This preliminary study has given rise to a multicenter study of compounding for ichthyosis. We expect that analysis of a larger sample will confirm our findings.
Subject(s)
Quality of Life , Rare Diseases , Cross-Sectional Studies , Drug Compounding , Humans , PharmacistsABSTRACT
INTRODUCTION: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. MATERIAL AND METHODS: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. RESULTS: The study included 15 patients with a median age of 17.8 years and were treated with nine different drugs: sapropterin, sodium phenylbutyrate, miglustat, velaglucerase, sebelipase, idursulfase, 5-hydroxytryptophan, succinate, and riboflavin. Seven different inborn errors of metabolism were observed: phenylketonuria, defects of the urea cycle, Gaucher, Nieman-Pick, Hunter's disease, along with acid lipase deficiency, and mitochondrial diseases. Orphan drugs used for the treatment of inborn errors of metabolism accounted for 1.3% of hospital drug costs. Some orphan drugs achieved asymptomatic patients, but others just produced a modest symptomatic improvement. Most patients showed good tolerance to the treatment. CONCLUSIONS: Orphan drugs used in inborn errors of metabolism had an easy to manage toxicity profile, with many disparities in effectiveness. These drugs have a high economic impact. The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence.
Subject(s)
Metabolic Diseases , Metabolism, Inborn Errors , Adolescent , Child , Humans , Metabolism, Inborn Errors/drug therapy , Orphan Drug Production , Rare Diseases/drug therapy , Retrospective StudiesABSTRACT
Introducción: Los errores congénitos del metabolismo son un grupo muy heterogéneo de enfermedades raras. La mayoría se pueden tratar con dieta y sustitución enzimática. Existen pocos pacientes y pocos estudios publicados en estas enfermedades. Por ello, se ha llevado a cabo un estudio con el objetivo de evaluar la efectividad de los medicamentos huérfanos utilizados en errores congénitos del metabolismo de un hospital general de 630 camas. Material y métodos: Estudio descriptivo restrospectivo de 24 meses de duración en un hospital general de 630 camas. Se incluyeron los pacientes diagnosticados durante la infancia de errores congénitos del metabolismo y que acudieron a Hospital de Día o a la consulta de Farmacia.(AU)
Introduction: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. Material and Methods: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. (AU)
Subject(s)
Humans , Child, Preschool , Child , Pediatrics , Metabolism, Inborn Errors , Orphan Drug ProductionABSTRACT
INTRODUCTION: Inborn errors of metabolism are a highly heterogeneous group of orphan diseases. Diet therapy and enzyme and coenzyme replacement are the most frequently used treatment. There are few patients and published studies about inborn errors of metabolism. The main objective of this study was to describe the effectiveness of orphan drugs in inborn errors of metabolism in paediatric patients. MATERIAL AND METHODS: Retrospective descriptive study of 24 months on patients diagnosed with inborn errors of metabolism during childhood and who attended the pharmacy clinic or Day-Care Unit of a 630-bed general hospital. RESULTS: The study included 15 patients with a median age of 17.8 years and were treated with nine different drugs: sapropterin, sodium phenylbutyrate, miglustat, velaglucerase, sebelipase, idursulfase, 5-hydroxytryptophan, succinate, and riboflavin. Nine different inborn errors of metabolism were observed: phenylketonuria, defects of the urea cycle, Gaucher, Nieman-Pick, Hunter's disease, along with acid lipase deficiency, and mitochondrial diseases. Orphan drugs used for the treatment of inborn errors of metabolism accounted for 1.3% of hospital drug costs. Some orphan drugs achieved asymptomatic patients, but others just produced a modest symptomatic improvement. Most patients showed good tolerance to the treatment. CONCLUSIONS: Orphan drugs used in inborn errors of metabolism had an easy to manage toxicity profile, with many disparities in effectiveness. These drugs have a high economic impact. The cost-effectiveness ratio for orphan drugs is a controversial issue due to their high cost and the inconclusive clinical evidence.
ABSTRACT
RESUMO A Resistência a Antimicrobianos (AMR) tem se revelado como um dos maiores problemas para a saúde pública no nível global. O objetivo deste artigo foi analisar a formulação da resposta à AMR negociada no âmbito da Organização Mundial da Saúde (OMS) por seus Estados-Membros. Foram analisados os relatórios e resoluções produzidos na Assembleia Mundial da Saúde no período de 1998 a 2019. Os achados indicam que, a partir de 2014, foram estabelecidas condições de possibilidade para a aprovação do Plano de Ação Global em AMR de forma mais robusta, abrangendo o conceito de Saúde Única e envolvendo outras instâncias internacionais (FAO, OIE, OMC e PNUMA). A análise dos conteúdos e o uso de diferentes referenciais analíticos, considerando dois setores econômicos - agropecuária e indústria farmacêutica -, mostraram-se relevantes para ilustrar a complexidade da temática, reforçando sua relevância global, reconhecendo a dimensão do uso de antibióticos em animais e as lacunas em inovação tecnológica. Como a OMS, além de ser um importante agente mobilizador para a resposta à AMR no nível global, tem garantido orçamento para ações nessa área mesmo em um contexto de desfinanciamento, conclui-se que a perspectiva da saúde pública deve prevalecer na resposta à AMR.
ABSTRACT Antimicrobial Resistance (AMR) has proved to be a major public health problem at the global level. This paper examined the formulation of the response to AMR negotiated through the World Health Organization (WHO) by its Member States. Related WHO reports and resolutions from 1998 to 2019 were analysed. The findings indicate that, from 2014 on, more robust conditions were established for approval of a Global Action Plan on AMR, encompassing the concept of One Health and involving other international entities (FAO, OIE, WTO and Unep). Content analysis and various analytical frameworks, considering two economic sectors (the livestock and pharmaceutical industries), proved relevant to illustrating the complexity of the issue, reinforcing its global importance and acknowledging the extent of antibiotic use in animals and the gaps in technological innovation. As the WHO is not only an important agent for mobilizing the response to AMR at the global level, but - despite a context of de-funding - has guaranteed a budget for action in this area, it is concluded that the public health perspective should prevail in the response to AMR.
Subject(s)
Benzoxazoles/therapeutic use , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Drug Development , Orphan Drug Production , Benzoxazoles/adverse effects , Benzoxazoles/economics , Cardiovascular Agents/adverse effects , Cardiovascular Agents/economics , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/economics , Cardiovascular Diseases/mortality , Cost-Benefit Analysis , Drug Approval , Drug Costs , Drug Development/economics , Humans , Orphan Drug Production/economics , Treatment OutcomeABSTRACT
ABSTRACT OBJECTIVES This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.
RESUMO OBJETIVOS O estudo examinou as aquisições de eculizumabe, um anticorpo monoclonal de alto custo utilizado no tratamento de doenças raras, pelos órgãos federais brasileiros, em termos das quantidades compradas, gastos e preços. MÉTODOS Foram analisadas compras de eculizumabe realizadas entre março de 2007 e dezembro de 2018, por meio de dados secundários extraídos do sistema de compras do governo federal (Siasg). Foram examinados o número de compras, quantidades adquiridas, número de doses diárias definidas por 1.000 habitantes por ano, gastos anuais e preços praticados. Os preços foram corrigidos pelo índice nacional de preços ao consumidor amplo para dezembro de 2018. Regressão linear foi utilizada para análises de tendência. RESULTADOS Todas as aquisições por órgãos federais foram realizadas pelo Ministério da Saúde. As compras se iniciaram em 2009, sendo efetuadas por dispensa de licitação e para atendimento de demanda judicial. Houve tendência crescente no número de compras e quantidades adquiridas ao longo do tempo. Foram realizadas 283 compras, totalizando 116.792 unidades adquiridas, 28,2% compradas em 2018. Os gastos totais contratados corrigidos somaram mais de R$ 2,44 bilhões. Após a aprovação do registro pela Agência Nacional de Vigilância Sanitária, o preço médio ponderado caiu aproximadamente 35%, para valores abaixo dos preços estabelecidos pela Câmara de Regulação do Mercado de Medicamentos. CONCLUSÃO O eculizumabe representou gastos extremamente significativos para o Ministério da Saúde no período. Todas as compras foram feitas para atendimento de demandas judiciais, fora do ambiente competitivo. Seu registro promoveu queda importante nos preços praticados. O estudo aponta a relevância do registro sanitário e da necessidade de monitoramento e auditoria permanentes das compras de medicamentos para atendimento de demandas judiciais.
Subject(s)
Humans , Health Expenditures , Federal Government , Antibodies, Monoclonal, Humanized/economics , Brazil , Drug and Narcotic Control/legislation & jurisprudence , Complement Inactivating Agents , Complement Inactivating Agents/economics , Government AgenciesABSTRACT
BACKGROUND: To assess uncertainty in regulatory decision-making for orphan medicinal products (OMP), a summary of the current basis for approval is required; a systematic grouping of medical conditions may be useful in summarizing information and issuing recommendations for practice. METHODS: A grouping of medical conditions with similar characteristics regarding the potential applicability of methods and designs was created using a consensus approach. The 125 dossiers for authorised OMP published between 1999 and 2014 on the EMA webpage were grouped accordingly and data was extracted from European Public Assessment Reports (EPARs) to assess the extent and robustness of the pivotal evidence supporting regulatory decisions. RESULTS: 88% (110/125) of OMP authorizations were based on clinical trials, with 35% (38/110) including replicated pivotal trials. The mean (SD) number of pivotal trials per indication was 1.4 (0.7), and the EPARs included a median of three additional non-pivotal supportive studies. 10% of OMPs (13/125) were authorised despite only negative pivotal trials. One-third of trials (53/159) did not include a control arm, one-third (50/159) did not use randomisation, half the trials (75/159) were open-label and 75% (119/159) used intermediate or surrogate variables as the main outcome. Chronic progressive conditions led by multiple system/organs, conditions with single acute episodes and progressive conditions led by one organ/system were the groups where the evidence deviated most from conventional standards. Conditions with recurrent acute episodes had the most robust datasets. The overall size of the exposed population at the time of authorisation of OMP - mean(SD) 190.5 (202.5) - was lower than that required for the qualification of clinically-relevant adverse reactions. CONCLUSIONS: The regulatory evidence supporting OMP authorization showed substantial uncertainties, including weak protection against errors, substantial use of designs unsuited for conclusions on causality, use of intermediate variables, lack of a priorism and insufficient safety data to quantify risks of relevant magnitude. Grouping medical conditions based on clinical features and their methodological requirements may facilitate specific methodological and regulatory recommendations for the study of OMP to strengthen the evidence base.
Subject(s)
Decision Making , Rare Diseases , Drug Approval , Europe , Humans , Orphan Drug ProductionABSTRACT
We find ourselves in an era of unprecedented growth in the development and use of so-called "orphan" drugs to treat rare diseases, which are poised to represent more than one-fifth of pharmaceutical expenditures by 2022. This widespread use has been facilitated by legislative and regulatory incentives in both the United States and abroad, yet US payers and health systems have not yet made a concerted effort to understand whether and how rare diseases require special considerations on their part and how to adapt traditional methods of health technology assessment and economic evaluation to accommodate these situations. In this article, we explore the general ethical dilemmas that rare diseases present, steps taken by health technology assessment bodies worldwide to define the level of rarity that would necessitate special measures and the modifications to their assessment and valuation processes needed, and the contextual components for rare-disease evaluation that lie outside of the assessment framework as a guide to US decision makers on constructing a formal and relevant process stateside.
Subject(s)
Cost-Benefit Analysis/economics , Orphan Drug Production/economics , Rare Diseases/economics , Decision Making , Health Expenditures/ethics , Humans , Orphan Drug Production/ethics , Rare Diseases/drug therapy , Technology Assessment, Biomedical/ethics , United StatesABSTRACT
BACKGROUND: Personalized medicine and orphan drugs share many characteristics-both target small patient populations, have uncertainties regarding efficacy and safety at payer submission, and frequently have high prices. Given personalized medicine's rising importance, this review summarizes international coverage and pricing strategies for personalized medicine and orphan drugs as well as their impact on therapy development incentives, payer budgets, and therapy access and utilization. METHODS: PubMed, Health Policy Reference Center, EconLit, Google Scholar, and references were searched through February 2017 for articles presenting primary data. RESULTS: Sixty-nine articles summarizing 42 countries' strategies were included. Therapy evaluation criteria varied between countries, as did patient cost-share. Payers primarily valued clinical effectiveness; cost was only considered by some. These differences result in inequities in orphan drug access, particularly in smaller and lower-income countries. The uncertain reimbursement process hinders diagnostic testing. Payer surveys identified lack of comparative effectiveness evidence as a chief complaint, while manufacturers sought more clarity on payer evidence requirements. Despite lack of strong evidence, orphan drugs largely receive positive coverage decisions, while personalized medicine diagnostics do not. CONCLUSIONS: As more personalized medicine and orphan drugs enter the market, registries can provide better quality evidence on their efficacy and safety. Payers need systematic assessment strategies that are communicated with more transparency. Further studies are necessary to compare the implications of different payer approaches.
Subject(s)
Insurance Coverage/statistics & numerical data , Insurance, Health/statistics & numerical data , Orphan Drug Production/economics , Precision Medicine/economics , Cost Sharing/statistics & numerical data , Cost-Benefit Analysis , Drug Costs/statistics & numerical data , Humans , Pharmacogenomic Testing/economics , Rare Diseases/drug therapyABSTRACT
ABSTRACT In the US, where registration of lobbyists is mandatory, the pharmaceutical industry and private health-care providers spend huge amounts of money seeking to influence health policies and government decisions. In Brazil, where lobbying lacks transparency, there is virtually no data on drug industry expenditure to persuade legislators and government officials of their viewpoints and to influence decision-making according to commercial interests. Since 1990, however, the Associação da Indústria Farmacêutica de Pesquisa (Interfarma - Pharmaceutical Research Industry Association), Brazilian counterpart of the Pharmaceutical Research and Manufacturers of America (PhRMA), main lobbying organization of the US pharmaceutical industry, has played a major role in the advocacy of interests of major drug companies. The main goals of Interfarma lobbying activities are: shortening the average time taken by the Brazilian regulatory agency (ANVISA) to approve marketing authorization for a new drug; making the criteria for incorporation of new drugs into SUS (Brazilian Unified Health System) more flexible and speeding up technology incorporation; changing the Country's ethical clearance system and the ethical requirements for clinical trials to meet the need of the innovative drug industry, and establishing a National Policy for Rare Diseases that allows a prompt incorporation of orphan drugs into SUS. Although lobbying affects community health and well-being, this topic is not in the public health research agenda. The impacts of pharmaceutical lobbying on health policies and health-care costs are of great importance for SUS and deserve to be investigated.
Subject(s)
Humans , Drug Approval/economics , Drug Approval/legislation & jurisprudence , Drug Industry/legislation & jurisprudence , Drug Industry/organization & administration , Lobbying , Persuasive Communication , Brazil , Public Health , Conflict of Interest/economics , Conflict of Interest/legislation & jurisprudenceABSTRACT
Partindo da definição e compreensão dos conceitos relacionados ao medicamento, às doenças raras e à ética, bem como à interface entre esses conceitos no bojo da reflexão do direito sanitário, são detalhadas e discutidas as excepcionalidades das drogas, destinadas a tratar doenças raras, definidas por padrões epidemiológicos nacionais e internacionais, como aquelas que afetam poucos indivíduos, proporcionalmente. Em seguida, examina-se o debate internacional acerca do fornecimento de medicamento pós-estudo, para concluir com a evocação do necessário compromisso ético.
Taking off from a definition and comprehension of concepts related to medication, rare diseases and ethics, as well as the interface of these concepts in the core of reflection on sanitary law, the details and exceptionalities of the orphan drugs, designed to treat rare diseases, defined by domestic and international epidemiological standards as those that proportionally affect few individuals. Below, we examine the international debate concerning the supply of medication post-study, to conclude by evoking the required ethical commitment.
Partiendo de la definición y la comprensión de los conceptos relacionados al medicamento, a las enfermedades raras y a la ética, así como a la interfaz entre estos conceptos en el nudo de la reflexión del Derecho Sanitario, son detalladas y discutidas las excepcionalidades de las drogas, destinadas a tratar enfermedades raras, definidas por patrones epidemiológicos nacionales e internacionales como aquellas que afectan a pocos individuos, proporcionalmente. Posteriormente, se examina el debate internacional a propósito de la provisión de medicamentos post-estudio, para concluir con la evocación del requerido compromiso ético.
Subject(s)
Humans , Male , Female , Ethics, Research , Human Experimentation , Pharmaceutical Services , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/economics , Pharmaceutical Preparations/supply & distribution , Rare Diseases , Biomedical Research , Health Law , Health SystemsABSTRACT
BACKGROUND/AIMS: The aim of this study was to investigate the inconveniences and potential improvements in the use of orphan drugs for the treatment of infectious diseases, as determined by a survey of medical professionals. METHODS: An email was sent twice to the members of the Korean Society for Chemotherapy, and an online survey was conducted. The data collected were analyzed in terms of the frequency of drug use and associated difficulties as well as the scope for improvement. RESULTS: A total of 77 medical professionals participated in this survey. Rabies vaccine (n = 52), rabies immunoglobulin (n = 47), and foscarnet injection (n = 43) were supplied mainly through the Korea Orphan Drug Center (KODC), while artesunate (n = 29), quinine sulfate capsule (n = 24), quinine dihydrochloride injection (n = 23), and quinidine gluconate injection (n = 21) were supplied mainly through the National Medical Center (NMC). Difficulties in obtaining orphan drugs through the KODC were related to the KODC drug retrieval system (n = 67, 95.7% of respondents), lack of supplies on holidays (n = 66, 94.3%), complicated application procedures and documents (n = 61, 87.1%), and shipping inconveniences (n = 61, 87.1%). With regard to the use of orphan drugs supplied through the NMC, 52 participants (98.1%) responded that a staff visit should be mandatory for obtaining the drugs. CONCLUSIONS: Antivirals and antimalarial drugs are major orphan drugs used for the treatment of rare infections. It is necessary to establish a more efficient system to ensure a stable supply of orphan drugs, including on holidays, to enhance the smart drug searching system, and to simplify related administrative procedures.
