Marketing authorisation and pricing of FDA-approved cancer drugs in Brazil: a retrospective analysis.

Background: Most cancer drugs enter the US market first. US Food and Drug Administration (FDA) approvals of new cancer drugs may influence regulatory decisions in other settings. The study examined whether characteristics of available evidence at FDA approval influenced time-to-marketing authorisation (MA) in Brazil, and price differences between the two countries. Methods: All new FDA-approved cancer drugs from 2010 to 2019 were matched to drugs with MA and prices approved in Brazil by December 2020. Characteristics of main studies, availability of randomised controlled trials (RCTs), overall survival (OS) benefit, added therapeutic benefit, and prices were compared. Findings: Fifty-six FDA-approved cancer drugs with matching indications received a MA at the Brazilian Health Regulatory Agency (Anvisa) after a median of 522 days following US approval (IQR: 351-932). Earlier authorisation in Brazil was associated with availability of RCT (median: 506 vs 760 days, p = 0.031) and evidence of OS benefit (390 vs 543 days, p = 0.019) at FDA approval. At Brazilian marketing authorisation, a greater proportion of cancer drugs had main RCTs (75% vs 60.7%) and OS benefit (42.9% vs 21.4%) than that in the US. Twenty-eight (50%) drugs did not demonstrate added therapeutic benefit over drugs for the same indication in Brazil. Median approved prices of new cancer drugs were 12.9% lower in Brazil compared to the US (adjusted by Purchasing Power Parity). However, for drugs with added therapeutic benefit median prices were 5.9% higher in Brazil compared to the US, while 17.9% lower for those without added benefit. Interpretation: High-quality clinical evidence accelerated the availability of cancer medicines in Brazil. The combination of marketing and pricing authorisation in Brazil may favour the approval of cancer drugs with better supporting evidence, and more meaningful clinical benefit albeit with variable degree of success in achieving lower prices compared to the US. Funding: None.

Medicines legislation and regulation in the United Kingdom 1500-2020.

The initial purposes of regulation of medicines in England, and latterly in the United Kingdom, were principally to raise government revenue, to discourage murder by poisoning and to regulate the activities of pharmacists. It was only much later that regulators sought to ensure that medicines were of good quality, reasonably safe, and at least somewhat effective, and to curtail misuse of drugs. Here we survey the history of the regulation of medicines and poisons in England from the perspective of clinicians with an interest in therapeutics.

Increasing tramadol utilisation under strict regulatory control of opioid prescribing - A cross-sectional study in Taiwan from 2002 through 2016.

BACKGROUND/PURPOSE: Prescribing of opioids to patients with non-cancer pain is strictly regulated in Taiwan, but tramadol is not included in the regulation on chronic opioid prescribing. This study aims to identify the utilization trend of prescribing tramadol and other opioid analgesics and investigate the influence of government regulation on opioid prescribing in Taiwan. METHODS: This cross-sectional study used the Taiwan National Health Insurance claims database and the cancer registry from 2001 through 2016. The annual number of adult opioid users, opioid utilization (Defined Daily Doses [DDDs]/1000 registrants) and the number of supply days were enumerated for each calendar year and stratified by cancer or non-cancer patients. Descriptive statistics were used to report the trends in utilization for each calendar year. RESULTS: The regulation strictly limited persistent use of opioids for patients with non-cancer pain, of which only a small proportion of fentanyl (20%) and morphine (<2%) users were prescribed with an annual number of supply days greater than 28 days. The annual utilization of morphine (6.4-53.5 vs. 1.1 to 9.6 DDD/1000 registrants) and fentanyl (8.3-37.0 vs. 0.16 to 1.8 DDD/1000 registrants) to patients with cancer was consistently higher than patients without cancer. In contrast to morphine and fentanyl, the utilization of tramadol prescribed to patients without cancer increased 92.2-fold (3.7-341.2 DDD/1000 registrants) from 2002 to 2016. CONCLUSION: The regulation in Taiwan limited the prescribing of selective opioids for patients with non-cancer pain and the substitution of tramadol for other opioids may have safety implications.

Perceptions and experiences of laws and regulations governing access to opioids in South, Southeast, East and Central Asia: A systematic review, critical interpretative synthesis and development of a conceptual framework.

BACKGROUND: Opioids are essential medicines. Despite international and national laws permitting availability, opioid access remains inadequate, particularly in South, Southeast, East and Central Asia. AIM: To review evidence of perceptions and experiences of regulatory enablers and barriers to opioid access in South, Southeast, East and Central Asia. DESIGN: Systematic review of post-2000 research according to PRISMA guidelines. Data were subjected to critical interpretive synthesis. International, national and sub-national barriers were organised developing a conceptual framework of opioid availability. DATA SOURCES: PsycINFO, Medline, Embase, The Cochrane Library. CINAHL, Complete and ASSIA from 2000 until 20th May 2019. RESULTS: 21/14097 studies included: quantitative n = 15, qualitative n = 3 and mixed-methods n = 3. Four barrier/enabler themes were developed: Legal, regulatory, socio-political; lack of laws explicitly enabling opioid access, restrictive international controls and clinician prescribing concerns. Opioid availability; limited availability, poor policymaker and clinician education regarding opioid benefits, poor continuity of supply. Opioid Accessibility; medicine costs, distance to prescribing centres. Prescribing; extensive bureaucratic barriers, lack of human resources for prescribing. We present a novel framework of a self-perpetuating model of inadequate opioid provision. The Single Convention on Narcotics provides the context of restrictive laws and negative attitudes amongst policymakers. A consequent lack of prescribers and clinicians' negative attitudes at sub-national levels, results in inadequate access to and use of opioids. Data of inadequate consumption informs annual requirement estimates used by the International Narcotics Control Board to determine future opioid availability. CONCLUSIONS: Regulatory and socio-political actions unintentionally limit opioid access. International and national laws explicitly enabling opioid access are required, to assuage concerns, promote training and appropriate prescribing.

Política de drogas e Saúde Coletiva: diálogos necessários / Política de drogas y Salud Colectiva: diálogos necesarios / Drug policy and Collective Health: necessary dialogues

A hegemonia atual das políticas de drogas ilícitas tem implicações à Saúde Coletiva que necessitam ser discutidas de forma aprofundada. Este ensaio procura explorar, à luz das melhores evidências, o impacto das políticas sobre drogas focadas na criminalização do plantio, comércio e consumo de substâncias psicoativas sobre a saúde das populações. O contexto de análise principal será o brasileiro. Os pontos principais abordados por este trabalho incluem a questão social das drogas e a definição do paradigma proibicionista, as evidências da relação insalubre entre tal paradigma e a saúde das populações, a problemática de um modelo de assistência aos usuários de substâncias psicoativas focado nas comunidades terapêuticas, e futuros caminhos a serem explorados na superação da proibição de drogas ilícitas como a principal forma de abordar a questão. Entre os principais elementos problemáticos da abordagem repressiva no contexto brasileiro podem ser destacados a violência e a mortalidade por homicídios, os impactos sanitários do encarceramento e o bloqueio de acesso ao sistema de saúde e a novas terapias derivadas de substâncias psicoativas atualmente proscritas. Como propostas de mudanças políticas futuras, ressalta-se a descriminalização do uso, posse e pequenas vendas de drogas; a redução da violência e da discriminação associadas ao policiamento; o foco em políticas de redução de danos; a abordagem das especificidades relacionadas ao gênero; incluir variáveis sociais como métrica do sucesso no tratamento do uso problemático de drogas. Concluindo, é relevante que a questão social e política das drogas se torne objeto de mais estudos no campo da Saúde Coletiva.

La hegemonía actual de las políticas de drogas ilícitas tiene implicaciones para la Salud Colectiva que necesitan discutirse profundamente. Este trabajo estudia, a la luz de las mejores evidencias, el impacto de las políticas sobre las drogas, enfocadas en la criminalización del cultivo, tráfico y consumo de sustancias psicoactivas, para la salud de la población. El contexto de análisis principal será el brasileño. Los puntos principales abordados por este trabajo incluyen: cuestión social de las drogas y la definición del paradigma prohibicionista; evidencias de la relación insana entre este paradigma y la salud de las poblaciones; así como la problemática de un modelo de asistencia a los consumidores de sustancias psicoactivas centrado en comunidades terapéuticas, y los futuros caminos que se exploran para que se supere la prohibición de las drogas ilícitas como la vía principal de abordaje de esta cuestión. Entre los elementos primordiales y problemáticos del enfoque represivo en el contexto brasileño se pueden destacar: violencia y mortalidad por homicidios; impactos sanitarios con conlleva el encarcelamiento y el bloqueo del acceso al sistema de salud; así como las nuevas terapias, derivadas de sustancias psicoactivas, actualmente proscritas. A modo de propuestas para posibles cambios políticos futuros, se resalta la descriminalización del consumo, posesión y venta de pequeñas cantidades de droga; la reducción de la violencia y discriminación, asociadas a la vigilancia policial; situar el centro de la cuestión en políticas de reducción de perjuicios para la salud; plantear las especificidades relacionadas con el género; así como incluir variables sociales como medir el éxito de los tratamientos relacionados con el consumo problemático de drogas. A modo de conclusión, es relevante que la cuestión social y política de las drogas se convierta en objeto de más estudios en el campo de la Salud Colectiva.

The current status of policies on illicit drugs has implications for Collective Health that need to be discussed in depth. This essay aims to explore, in light of the best evidence, the public health impact of drug policies focused on the criminalization of growing, selling, and consuming psychoactive substances. Brazil provides the context for the main analysis. The principal points addressed in this work include drugs as a social issue and the definition of the prohibitionist paradigm, evidence of the unhealthy relationship between this paradigm and the population's health, the issue of a model of care for users of psychoactive substances focused on therapeutic communities, and future paths to be explored to overcome the prohibition of illicit drugs as the principal approach to the issue. Among the main problematic elements in the repressive approach in the Brazilian context, the study highlights violence and homicides, the health impacts of incarceration and blocked access to the health system, and potential new therapies derived from currently banned psychoactive substances. As proposals for future policy changes, the study highlights decriminalization of the use, possession, and small-scale sale of drugs; the reduction of the violence and discrimination associated with policing; focus on harm reduction policies; approach to gender-related specificities; and inclusion of social variables as metrics for successful treatment of problematic drug use. In conclusion, it is relevant that the social issue and drug policy have become the object of more studies in the field of Collective Health.

A Method for Approximating Future Entry of Generic Drugs.

OBJECTIVES: To develop and test a method for approximating generic entry of top-selling drugs. METHODS: The procedure involved 1) identifying products' key patents as those with a patent term restoration extension (whenever relevant) or otherwise as the first expiring patent listed in the US Food and Drug Administration's patent register, 2) determining whether the key patent had been extended through an associated pediatric extension, 3) identifying other regulatory exclusivities associated with the drug, and 4) categorizing key patents as active ingredient (or extended) patents versus secondary patents. The accuracy and precision of the procedure's predictions were then tested against a database containing the timing of generic entry for 170 top-selling drugs that lost market exclusivity between 2000 and 2012, on the basis of Medicaid data. RESULTS: Overall, the procedure predicted a median market exclusivity period of 12.5 years (interquartile range [IQR] 7.25-14.5) compared with the median actual period of 12.5 years (IQR 8.5-14.75 years). Among the 131 drugs (77%) with active ingredient patents, the median predicted market exclusivity was 12.25 years (IQR 7.5-14.5) compared with a median actual period of 13.0 years (IQR 10.0-14.75). Among the 38 (22%) drugs protected only by secondary patents, the median predicted market exclusivity was 16.0 years (IQR 6.75-19.5), but the median actual market exclusivity was only 8.25 years (IQR 6.25-13.5). CONCLUSIONS: The procedure approximated median actual exclusivity with reasonable accuracy and precision for drugs with active ingredient patents, but substantially overestimated exclusivity for drugs with only secondary patents.

Avanços e desafios em normatização de amostras grátis de medicamentos no Brasil / Advances and challenges in standardization of free samples of drugs in Brazil

Este trabalho analisou criticamente a legislação sobre amostras grátis de medicamentos no Brasil, pontuando alguns aspectos importantes relacionados à saúde da população. Foi realizado um levantamento das leis, decretos, normas e regulamentações que norteiam o assunto. A amostra grátis é uma das estratégias de publicidade e marketing usadas pela indústria farmacêutica. Em alguns casos, a indicação de certos medicamentos é baseada em dados técnicos apresentados pelos propagandistas. Por outro lado, os médicos que buscam informações técnicas em fontes com menor influência da indústria farmacêutica indicam menos os medicamentos novos, que na maioria das vezes são mais caros. Embora tenha sido observado um avanço na normatização em relação às amostras grátis, ela ainda é incipiente. Tópicos como o prazo mínimo para sua distribuição, quantidade máxima a ser entregue a cada prescritor, seu transporte, armazenamento e cuidados com o prazo de validade deveriam ser incluídas na legislação pertinente, como ocorre em outros países. Estas discussões deveriam ser retomadas com a menor influência possível dos laboratórios farmacêuticos, seguindo critérios técnico-científicos. Portanto, é necessário que este assunto seja contextualizado nas resoluções sobre amostras grátis de medicamentos, seguindo as normas das boas práticas de fabricação...

This paper critically analyzed the legislation on free samples of medicines in Brazil, scoring some important health-related aspects of the population. A survey of laws, decrees, rules and regulations that guide the subject was conducted. The free sample is one of the advertising and marketing strategies used by the pharmaceutical industry. In some cases, the designation of certain drugs is based on technical data provided by the propagandists. On the other hand, physicians seeking technical information on sources with less influence of the pharmaceutical industry indicate fewer new drugs, which most often are more expensive. Although an improvement in standardization has been seen for free samples, it is still incipient. Topics such as the time limit for its distribution, maximum to be delivered to each prescriber, transport, storage and care of the expiration date amount should be included in the relevant legislation, as in other countries. These discussions should be resumed with the least possible influence of pharmaceutical companies, following technical and scientific criteria. Therefore, it is necessary that this matter be contextualized in resolutions on free samples of medicines, following the standards of good manufacturing practices...

Avaliação da conformidade de prescrições médicas e dispensação de antimicrobianos / Conformity assessment of medical prescriptions and dispensation of antimicrobials / Evaluación de la conformidad de prescripción médica y dispensación de antimicrobianos

Avaliar a conformidade das prescrições médicas e a dispensação de antimicrobianos. Métodos: Estudo observacional e descritivo, que analisou as segundas vias de todas as prescrições médicas de antimicrobianos retidas em uma farmácia em São Luís- MA, no período de março a maio de 2012. Avaliaram-se 563 prescrições, de acordo com a exigência da legislação: legibilidade dos dados; identificação do emitente e do paciente; nome, quantidade, forma farmacêutica, dosagem e posologia; data de emissão e dispensação; percentagem dos medicamentos; número médio de medicamentos por prescrição e presença de interações medicamentosas. Resultados: Encontrou-se prescrição de 1.192 medicamentos, sendo 631 (53,2%) antimicrobianos. Classificaram-se as prescrições como legíveis (n=526; 93,60%), parcialmente legíveis (n=31; 51%) e completamente ilegíveis (n=5; 0,89%); 1,78% (n=10) apresentaram rasuras; 15,45% (n=86) não possuíam data de emissão; e 6,57% (n=36) estavam vencidas. Quatro dados de presença obrigatória na prescrição médica estavam ausentes em mais de 90% das prescrições avaliadas (o endereço e o telefone do emitente e a idade e o sexo do paciente). A ausência de duas das variáveis cujo registro é obrigatório na dispensação de antimicrobianos foi observada em 100% das prescrições avaliadas (número do lote do medicamento dispensado e a rubrica do farmacêutico). Os antimicrobianos mais prescritos foram amoxicilina (n=220; 34,87%), metronidazol (n=136; 21,55%) e neomicina (n=81; 12,84%). Identificaram-se interações medicamentosas moderadas (n=23; 4,08%) e leves (n=4; 0,72%). Conclusão: Os resultados do presente estudo demonstram a não conformidade tanto das prescrições médicas avaliadas como do processo de dispensação das prescrições em relação à legislação vigente...

To evaluate the conformity of medical prescriptions and the dispensation ofantimicrobials. Methods: Observational and descriptive study that analyzed the duplicates of all medical prescriptions of antimicrobials retained in a drugstore in São Luís-MA, from March to May 2012. A total of 563 prescriptions were evaluated according to the legislation guidelines: data readability; identification of issuer and patient; name; quantity; pharmaceutical form; dosage and posology; date of issue and dispensation; percentage of medications; average number of medicines per prescription and occurrence of drug interactions. Results: A total of 1192 medicines, including 631 (53.2%) antimicrobials were found. The prescriptions were classified as readable (n=526; 93.60%), partially readable (n=31; 51%) and completely unreadable (n=5; 0.89%); 1.78% (n=10) presented erasures; 15.45% (n=86) did not present date of issue; and 6.57% (n=36) were out of date. Four data of compulsory identification were missing in over 90% of the prescriptions assessed (issuer?s address and phone number and patient?s age and sex). The absence of two of the variables required in the dispensation of antimicrobials was observed in 100% of the prescriptions assessed (Medicine batch number and the pharmacist?s signature). The most commonly prescribed antimicrobials were amoxicillin (n=220; 34.87%), metronidazole (n=136; 21.55%) and neomycin (n=81; 12.84%). Moderate (n=23; 4.08%) and minor (n=4; 0.72%) drug interactions were identified. Conclusion: The results of the present study demonstratethe non-compliance of both the medical prescriptions assessed and the dispensation process with the current legislation...

Evaluar la conformidad de las prescripciones médicas y la dispensación de antimicrobianos. Métodos: Estudio observacional y descriptivo que analizó las segundas vías de todas las prescripciones médicas de antimicrobianos retenidas em uma farmacia de São Luís-MA en el período entre marzo y mayo de 2012. Fueron evaluadas 563 prescripciones según la exigencia de la legislación: legibilidad de los datos; identificación del emisor y del paciente; nombre, cantidad, forma farmacéutica, dosificación y posología; fecha de emisión y dispensación; porcentaje de los medicamentos; número medio de medicamentos por prescripción y presencia de interacciones medicamentosas. Resultados: Fueron encontradas prescripciones de 1.192 medicamentos y de ellos 631 (53,2%) antimicrobianos. Se clasificaron las prescripciones como legibles (n=526; 93,60%), legibles en parte (n=31; 51%) y totalmente ilegibles (n=5; 0,89%); el 1,78% (n=10) presentaron tachones; el 15,45% (n=86) no tenían fecha de emisión y El 6,57% (n=36) estaban caducadas. Cuatro datos obligatorios em la prescripción médica estaban ausentes en más del 90% de lãs prescripciones evaluadas (la dirección y el número de teléfono Del emisor y la edad y el sexo del paciente). La ausencia de dos de las variables cuyo registro es obligatorio en la dispensación de antimicrobianos fue observada en el 100% de las prescripcionesevaluadas (número del lote del medicamento dispensado y la rúbrica del farmacéutico). Los antimicrobianos más prescritos fueron la amoxicilina (n=220; 34,87%), el metronidazol (n=136; 21,55%) y la neomicina (n=81; 12,84%). Se identificaron interacciones medicamentosas moderadas (n=23; 4,08%) y leves (n=4; 0,72%). Conclusión: Los resultados del presente estúdio demostraron la no conformidad de las prescripciones médicas evaluadas y del proceso de dispensación de las prescripciones respecto la legislación vigente...

Potential Regulatory and Commercial Environment for Biosimilars in Latin America.

OBJECTIVES: Biosimilars are increasingly attractive to payers around the globe because of mounting financial pressure. Many Latin American governments are developing abbreviated regulatory pathways for biosimilars. There are limited data regarding how certain regulatory agencies in the region plan to address biosimilar access. This study explores potential opportunities and challenges for biosimilar drugs in Brazil, Mexico, Argentina, Chile, and Venezuela. METHODS: We conducted targeted literature reviews, followed by key informant interviews, to understand the expected regulatory environment for biosimilars. We also asked questions about the economic, political, and historical factors that could play a role in the extent to which biosimilar-specific pathways have been developed across countries to date, and will continue to evolve in the future. RESULTS: Brazil has led the development of biosimilar regulation in Latin America, with two distinct pathways, one for more complex molecules such as monoclonal antibodies and a less rigorous path for simpler molecules such as pegylated interferon and low molecular weight heparin. Other countries have been slower to respond, in part because of the degree of emphasis within each country for the advancement of biosimilar regulatory standards. Signs of relaxed standards akin to those seen in Brazil's "individual development" pathway were found in other countries. CONCLUSIONS: The example of the two-pathway system coupled with governmental prioritization of local manufacturing capabilities in Brazil should promote increased biosimilar utilization within the country. Assuming that the two-pathway system demonstrates success in Brazil, we hypothesize that other Latin American countries may adapt aspects of this "local" model for developing a regulatory pathway for biosimilars.