Supervisión de ensayos clínicos en hospitales del Seguro Social de Salud del Perú: enfoque administrativo y regulatorio / Supervision of clinical trials in Social Health Insurance at Peruvian Hospitals: administrative and regulatory approach

RESUMEN El objetivo del estudio fue describir las características de los ensayos clínicos (EC) supervisados por el Instituto de Evaluación de Tecnologías en Salud e Investigación en EsSalud entre el 2015 y 2018 y las principales observaciones de las supervisiones realizadas. Se realizó un estudio descriptivo de 82 ensayos clínicos supervisados entre 2015 y 2018. La mayoría de los ensayos clínicos fueron estudios de fase III (81,7%), la vía de administración más frecuente de los productos de estudio fue oral (47,6%) y la mayoría fueron patrocinados por la industria farmacéutica (96,3%). Las observaciones más frecuentes fueron las relacionadas al contrato de estudio (83,8%), al pago por concepto de overhead (57,3%) y a la falta de documentos regulatorios (47,6%). Estos hallazgos permiten la identificación de oportunidades de mejora en la regulación y gestión de la investigación.

ABSTRACT The objective of the study was to describe the characteristics of the Clinical Trials (CT) supervised by the Institute of Health Technology Assessment and Research carried out in EsSalud between 2015 and 2018 and the main observations of the supervisions completed. A descriptive study of 82 supervised clinical trials was conducted between 2015 and 2018. Most of the clinical trials were phase III studies (81.7%); the most frequent route of administration of the study products was oral (47.6%), and most were sponsored by the pharmaceutical industry (96.3%). The most frequent observations were those related to the study contract (83.8%), overhead payment (57.3%), and the lack of regulatory documents (47.6%). These findings allow the identification of opportunities for improvement in research regulation and management.

III. The role of the Research Ethics Committees in the regulation of Pharma-Sponsored studies

Participants of Pharma-sponsored research are exposed to risks, benefits, and uncertainties that do not occur in other forms of clinical studies. Ethics committees represent the subjects’ first line of protection. This responsibility begins with the study review and ends after all study subjects finish the intervention. The objective of this paper is to review the most common controversial issues found in Pharma-sponsored studies. Potential solutions are proposed to prevent or resolve the polemical aspects. However, different challenges will be faced in the near future (e.g., when new therapies reach their late stage of development). All parties involved in research should work together to guarantee the protection of participants, the paramount principle on which clinical investigation is based. Pharma-sponsored research is a crucial driver to develop and implement innovative approaches to improve the informed consent process and the execution of the studies.

Importancia de la investigación clínica independiente en la medicina: dificultades y recomendaciones / Importance of independent clinical research in medicine: difficulties and recommendations

Resumen La investigación clínica es la herramienta de mayor importancia para la identificación de estrategias diagnósticas y terapéuticas que deriven en mayor eficacia y seguridad. A pesar de su trascendencia, la implementación exitosa de la investigación clínica presenta numerosas dificultades; entre las más relevantes se encuentra la poca disponibilidad de recursos para realizar ensayos clínicos independientes. Por lo general, la industria farmacéutica absorbe los costos asociados con la mayoría de los ensayos clínicos, sin embargo, esto puede generar una disociación entre los temas de interés y las prioridades en salud, al existir interés económico como principal motivación de estos protocolos. Además del papel relevante de la industria farmacéutica, es importante que las instancias gubernamentales favorezcan las condiciones, tanto económicas como regulatorias, para la implementación de investigación clínica independiente, que aborde temas de interés médico y terapéutico, aunque no genere beneficios económicos empresariales.

Abstract Clinical research is the most important tool for the identification of diagnostic and therapeutic strategies that derive in higher efficacy and safety. Despite its significance, successful implementation of clinical research faces numerous difficulties, with one the most relevant being limited availability of resources for the performance of independent clinical trials. Generally, the pharmaceutical industry absorbs the costs associated with most clinical trials; however, this can generate dissociation between subjects of interest and health priorities when economic interest is the main driver of these protocols. In addition to the relevant role played by the pharmaceutical industry, it is important that government agencies favor adequate conditions, both in economic and regulatory aspects, for the implementation of independent clinical research that addresses subjects of medical and therapeutic interest, even if it does not generate corporate economic benefits.

New regulations on compensation for injury and death in drug trials.

In 2005, the government amended Schedule Y of the Drugs and Cosmetics Act, 1940, and Rules, 1945, to liberalise the conduct of global drug trials in India. Proponents of this policy had asserted that we needed less, and not more, regulation, in order to expand the business of drug trials. Many from the medical profession, the bioethics community and civil society groups have been critical of this policy.

Book review : Of snowstorms, swordfights and blood trails: the underbelly of clinical trials.

The world of clinical trials is ethically fragile. Huge amounts of money are at stake and a handful of people are privy to a lot of confidential information about the trials. This imbalance in money and knowledge sometimes results in an unholynexus. Known as insider trading, progress reports of a trial are sometimes passed on to investors so that they can augment or deplete their share in the investment before the trial results are officially made public. The person(s) passing on the information would also have vested interests in the profits. This unmitigatedly unethical practice is explored by the book, using the genre of a murder thriller.

Biopharmaceutical industry-sponsored global clinical trials in emerging countries / Ensaios clínicos globais patrocinados pela indústria biofarmacêutica em países emergentes

OBJECTIVE: To evaluate biopharmaceutical industry-sponsored clinical trials placed in countries previously described as emerging regions for clinical research, and potential differences for those placed in Brazil. METHODS: Data regarding recruitment of subjects for clinical trials were retrieved from www.clinicaltrials.gov on February 2nd 2009. Proportions of sites in each country were compared among emerging countries. Multiple logistic regressions were performed to evaluate whether trial placement in Brazil could be predicted by trial location in other countries and/or by trial features. RESULTS: A total of 8,501 trials were then active and 1,170 (13.8 percent) included sites in emerging countries (i.e., Argentina, Brazil, China, Czech Republic, Hungary, India, Mexico, Poland, Russia, South Korea, and South Africa). South Korea and China presented a significantly higher proportion of sites when compared to other countries (p<0.05). Multiple logistic regressions detected no negative correlation between placement in other countries when compared to Brazil. Trials involving subjects with less than 15 years of age, those with targeted recruitment of at least 1,000 subjects, and seven sponsors were identified as significant predictors of trial placement in Brazil. CONCLUSION: No clear direct competition between Brazil and other emerging countries was detected. South Korea showed the higher proportion of sites and ranked third in total number of trials, appearing as a major player in attractiveness for biopharmaceutical industry-sponsored clinical trials.

OBJETIVO: Avaliar ensaios clínicos patrocinados pela indústria biofarmacêutica alocados em países previamente definidos como emergentes em pesquisa clínica e possíveis diferenças naqueles alocados no Brasil. MÉTODOS: Dados de ensaios clínicos recrutando pacientes foram obtidos (www.clinicaltrials.gov) em 2 de fevereiro de 2009. As proporções de centros em cada país foram comparadas entre os países emergentes. Regressões logísticas múltiplas foram realizadas para avaliar a alocação do ensaio em outros países emergentes e as características do ensaio como preditores da presença de algum centro no Brasil RESULTADOS: No total, 8.501 ensaios clínicos estavam ativos à época, e 13,8 por cento destes (N=1.170) incluíam centros em países emergentes (i.e., Argentina, Brasil, China, República Tcheca, Hungria, Índia, México, Polônia, Rússia, Coreia do Sul, e África do Sul). Coreia do Sul e China apresentaram uma proporção de centros significativamente superior aos outros países (p<0,05). Não se detectou correlação negativa na alocação de ensaios no Brasil quando comparada com outros países. Ensaios envolvendo sujeitos com idade menor que 15 anos, com o recrutamento planejado de pelo menos 1.000 sujeitos e sete patrocinadores, foram identificados como preditores significativos da alocação de centros no Brasil. CONCLUSÃO: Não se detectou competição direta entre o Brasil e outro país emergente. A Coreia do Sul apresentou a maior proporção de centros e foi o terceiro país em número total de ensaios, demonstrando ser um importante país em termos de atratividade para ensaios clínicos patrocinados pela indústria biofarmacêutica.

Custo-efetividade do tratamento da anemia em pacientes renais em terapia renal substitutiva no Brasil / Cost-effectiveness of treating anemia in kidney patients on renal replacement therapy in Brazil

O estudo teve como objetivo avaliar a razão de custo-efetividade, sob a perspectiva do Sistema Único de Saúde - SUS, do tratamento da anemia de pacientes em Terapia Renal Substitutiva. Duas alternativas foram comparadas: um novo medicamento recentemente registrado no Brasil, o Ativador Contínuo de Receptor de Eritropoetina (Continuous Erythropoitin Receptor Activador), CERA, e outro, atualmente disponível no sistema de saúde brasileiro, a Eritropoetina Recombinante Humana - EPO-rHu. Métodos: Um modelo de Markov simulou o curso de uma coorte de pacientes em Terapia Renal Substitutiva tratados com CERA e Epo-Hu por quatro anos. A qualidade de vida associada ao uso dos medicamentos foi estimada de forma indireta, por meio de entrevista qualificada com os profissionais cuidadores, previamente submetida e aprovada pelo Comitê de Ética em Pesquisa local. Foi realizada análise de sensibilidade no modelo proposto através da variação dos parâmetros: doses dos medicamentos, custo das estratégias, taxas de desconto e efetividade utilizados para sua construção. Resultados: A média da qualidade de vida atribuída aos pacientes tratados foi 6,3 para Epo-rHu, 7,8 para o CERA e 9,3 para os pacientes transplantados. O modelo demonstrou que a estratégia mais custo-efetiva é a terapêutica com a Epo-rHu, com um custo por QALY de R$21.052,00. O custo incremental por QALY ganho associado ao CERA foi de 72.974,00. Conclusão: A utilização mensal do medicamento CERA está associada à maior qualidade de vida quando comparada a EPO-rHu. No entanto, a terapia com o novo medicamento não se mostrou mais custo-efetiva frente ao tratamento com EPO-rHu.

Reflexiones en torno a la publicación de resultados de ensayos clínicos realizados en la provincia Villa Clara / Reflections on publication results of clinical trials carried out at Las Villas province

La producción científica relacionada con los ensayos clínicos en el territorio de Villa Clara creció considerablemente durante los años 2007-2008, un período en el que se publicó un total de 25 artículos científicos en revistas nacionales acreditadas por el Ministerio de Ciencia, Tecnología y Medio Ambiente (CITMA) y extranjeras, procesadas por bases de datos de reconocido prestigio...

Pharmacoeconomics.

Pharmacoeconomics focuses on the costs and benefits of drug therapy and pharmacoeconomic evaluations provide a basis for resource allocation and utilization. It is increasingly becoming important for health policy decision-making. A pharmacoeconomic evaluation may be conducted as an economic assessment incorporated into clinical trials. Such trials should compare the new drug/procedure with an older drug or existing intervention. Four techniques are used for economic evaluation, namely, cost-minimization analysis, cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis. The choice of the evaluation method depends on the nature of outcomes and the context in which the choices need to be made. Pharmacoeconomics is a young science that will improve with application. Its need is undeniable, especially in developing countries.

A cost-effectiveness analysis of three antimalarial treatments for acute, uncomplicated Plasmodium falciparum malaria in Mumbai, India.

BACKGROUND: Malaria is a major public health problem representing 2.3% of the overall global disease burden. The cost of treatment of malaria continues to rise as older drugs and insecticides become less effective and are replaced by more effective, but also more expensive products. METHODS: A post-hoc pharmacoeconomic analysis (direct and indirect costs only) of three antimalarials, chloroquine, mefloquine and co-artemether, was carried out to address the problem of switch to a more expensive first-line antimalarial in the face of growing chloroquine resistance. RESULTS: From the perspective of a large public hospital, it was seen that in an area of high grade chloroquine resistance, the total expenditure on patients who fail chloroquine would exceed the excess expenditure on mefloquine when the RII + RIII resistance exceeded 9%. CONCLUSIONS: Switch to a more expensive drug like mefloquine as a first-line option would be cost-effective when the moderate-severe chloroquine resistance exceeded 9%.