RESUMO
This Viewpoint discusses the benefits of expanded access research, the usefulness of expanded access data, the issues surrounding cost and transparency, and the adjusted role of institutional review boards.
Assuntos
Pesquisa Biomédica , Ensaios de Uso Compassivo , Comitês de Ética em Pesquisa , Ética em Pesquisa , Comitês de Ética em Pesquisa/ética , Ensaios de Uso Compassivo/ética , Pesquisa Biomédica/éticaAssuntos
Ensaios de Uso Compassivo/legislação & jurisprudência , Procedimentos Ortopédicos/legislação & jurisprudência , Direitos do Paciente/legislação & jurisprudência , Segurança do Paciente/legislação & jurisprudência , United States Food and Drug Administration/legislação & jurisprudência , Ensaios de Uso Compassivo/ética , Humanos , Procedimentos Ortopédicos/ética , Direitos do Paciente/ética , Estados UnidosRESUMO
The Covid-19 pandemic creates an unprecedented threatening situation worldwide with an urgent need for critical reflection and new knowledge production, but also a need for imminent action despite prevailing knowledge gaps and multilevel uncertainty. With regard to the role of research ethics in these pandemic times some argue in favor of exceptionalism, others, including the authors of this paper, emphasize the urgent need to remain committed to core ethical principles and fundamental human rights obligations all reflected in research regulations and guidelines carefully crafted over time. In this paper we disentangle some of the arguments put forward in the ongoing debate about Covid-19 human challenge studies (CHIs) and the concomitant role of health-related research ethics in pandemic times. We suggest it might be helpful to think through a lens differentiating between risk, strict uncertainty and ignorance. We provide some examples of lessons learned by harm done in the name of research in the past and discuss the relevance of this legacy in the current situation.
Assuntos
COVID-19/epidemiologia , Ética em Pesquisa , Pesquisa Biomédica/ética , COVID-19/terapia , Ensaios de Uso Compassivo/ética , Direitos Humanos/ética , Humanos , IncertezaAssuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Ensaios de Uso Compassivo , Reposicionamento de Medicamentos/métodos , Controle de Medicamentos e Entorpecentes , Drogas em Investigação , Acessibilidade aos Serviços de Saúde , COVID-19/epidemiologia , Ensaios de Uso Compassivo/ética , Ensaios de Uso Compassivo/métodos , Ensaios de Uso Compassivo/normas , Aprovação de Drogas/métodos , Controle de Medicamentos e Entorpecentes/organização & administração , Controle de Medicamentos e Entorpecentes/tendências , Drogas em Investigação/provisão & distribuição , Drogas em Investigação/uso terapêutico , Serviços Médicos de Emergência/ética , Serviços Médicos de Emergência/métodos , Acessibilidade aos Serviços de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/tendências , Humanos , Internacionalidade , Papel do Médico , Medição de Risco , SARS-CoV-2Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , COVID-19 , Ensaios Clínicos como Assunto/ética , Ensaios Clínicos como Assunto/métodos , Ensaios de Uso Compassivo/ética , Ensaios de Uso Compassivo/métodos , Reposicionamento de Medicamentos/ética , Reposicionamento de Medicamentos/métodos , Drogas em Investigação/uso terapêutico , Vacinas contra Ebola/uso terapêutico , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/terapia , Humanos , SARS-CoV-2RESUMO
BACKGROUND: Nowadays one of the most critical aspects of innovative cell-based therapies is the unregulated industry, as it is becoming a competitor of the regulated system. Many private clinics, worldwide, advertise and offer cell-based interventions treatments directly to the consumer and this poses a risk to both vulnerable patients and health systems. Several countries have implemented Compassionate Use Programmes (CUP) that provide patients with medicines that have not yet completed the approval pathway, in the event that no reasonable alternative exists. Recently, in the public discourse, compassionate use has been increasingly associated with a patient's right to try. Thus, the aim of this study was to assess public knowledge of the clinical trials process with specific reference to innovative stem cell treatments, and trust in the institutions responsible for regulatory activities. We also asked people about their "right" to use unregulated therapies. METHODS: We developed an ad hoc questionnaire on three main areas of concern and administered it to 300 people in the patient waiting room at an Italian university hospital. RESULTS: Our findings suggest that people have a good knowledge of the clinical trials process and trust in healthcare institutions. Nonetheless, one person in two believes it is a right to use unregulated therapies. CONCLUSIONS: We stress the need, in the age of cellular therapies, for a commitment to support vulnerable patients and to strengthen awareness among the public about the substantial boundary that differentiates experimental therapies from unproven therapies. There should not be a "right to try" something that is unsafe but rather approved treatments and in line with good clinical practice. The trend, which emerged on this issue from our study, is quite different, confirming the urgent need to improve health information so that it is as complete as possible.
Assuntos
Ensaios de Uso Compassivo , Direitos do Paciente , Direito à Saúde , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo/ética , Ensaios de Uso Compassivo/legislação & jurisprudência , Cultura , União Europeia , Feminino , Humanos , Itália , Masculino , Turismo Médico , Pessoa de Meia-Idade , Direitos do Paciente/ética , Direitos do Paciente/legislação & jurisprudência , Segurança do Paciente , Direito à Saúde/ética , Direito à Saúde/legislação & jurisprudência , Risco , Transplante de Células-Tronco/ética , Transplante de Células-Tronco/legislação & jurisprudência , Terapias em Estudo/ética , Confiança , Estados Unidos , Adulto JovemAssuntos
Ensaios de Uso Compassivo , Terapia Genética , Ensaios de Uso Compassivo/economia , Ensaios de Uso Compassivo/ética , Ensaios de Uso Compassivo/legislação & jurisprudência , Terapia Genética/economia , Terapia Genética/ética , Terapia Genética/legislação & jurisprudência , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMO
In this commentary, we raise concerns about the compassionate use of CRISPR-mediated gene therapies in pediatric and perinatal patients. There is already a precedent for obtaining gene therapies for pediatric patients through compassionate use programs, and the recent passage of a federal Right to Try law may contribute to an increase in the number of patients who seek access to investigational products outside of a clinical trial. Clinicians, nurses, drug companies, and parents need support as they grapple with whether compassionate use of CRISPR-mediated gene therapies is the right thing to pursue for a child. We raise three issues to consider in that decision: (1) the effects of compassionate use on scientific research; (2) hype and harms of gene therapies; and (3) the limits and scope of parental authority.
Assuntos
Sistemas CRISPR-Cas , Ensaios de Uso Compassivo/ética , Análise Ética , Terapia Genética/ética , Leucemia/terapia , Tomada de Decisões , Humanos , Lactente , Leucemia/genética , Leucemia/imunologia , Pediatria , Indução de Remissão , Resultado do TratamentoAssuntos
Células-Tronco Adultas/transplante , Ensaios Clínicos como Assunto/normas , Insuficiência Cardíaca/terapia , Células-Tronco Pluripotentes Induzidas/transplante , Células-Tronco Adultas/citologia , Reprogramação Celular , Ensaios Clínicos como Assunto/ética , Ensaios de Uso Compassivo/ética , Ensaios de Uso Compassivo/normas , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/cirurgia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Japão , Miócitos Cardíacos/citologia , Miócitos Cardíacos/transplante , Segurança do PacienteRESUMO
Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or 'preapproval', access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients' best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee (CompAC). Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice.
Assuntos
Tomada de Decisão Clínica/ética , Ensaios de Uso Compassivo/ética , Indústria Farmacêutica/ética , Drogas em Investigação/uso terapêutico , Relações Interprofissionais , Centros Médicos Acadêmicos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto/ética , Indústria Farmacêutica/organização & administração , Drogas em Investigação/provisão & distribuição , Comitês de Ética em Pesquisa/organização & administração , Ética Médica , Ética Farmacêutica , Humanos , Mieloma Múltiplo/tratamento farmacológico , Projetos PilotoRESUMO
There are increasing demands on regulators and insurers internationally to provide access to medicines more quickly, and often on the basis of less robust evidence of safety, efficacy or cost-effectiveness than have traditionally been required. These demands arise from a number of sources, including those advocating for access to medicines for patients with life-threatening diseases, rare diseases, or subsets of common diseases and where entire populations are threatened in the context of public health emergencies. In response to these demands, policymakers have instituted a number of initiatives aimed at speeding up access to medicines, which we refer to collectively as "accelerated access" programs. While there are strong arguments for accelerated access programs, these programs also raise a number of socio-political, epistemic and moral issues. Some of these issues are common to all types of accelerated access programs, while others are specific to particular types of accelerated access. Here, we offer a conceptual framework that highlights ethically relevant similarities and differences among different kinds of accelerated access processes for the purpose of enabling ethically and politically-informed policy making.
Assuntos
Ensaios de Uso Compassivo/ética , Drogas em Investigação/uso terapêutico , Ensaios de Uso Compassivo/economia , Drogas em Investigação/economia , Equidade em Saúde , Política de Saúde , Acessibilidade aos Serviços de Saúde/ética , Consentimento Livre e EsclarecidoRESUMO
BACKGROUND: Today, public and private bodies around the world are trying to facilitate and increase expanded access to unapproved, investigational drugs for patients with unmet medical needs. METHODS: This paper discusses three major shifts in the field of expanded access and presents an argumentative account of ethical issues connected with those shifts, based on a literature study and unstructured interviews with 35 stakeholders in the Netherlands. RESULTS AND DISCUSSION: Traditionally, expanded access has been based on three key principles: 1) it is exceptional, 2) it is done 'out of compassion', and 3) it has a therapeutic aim. Current efforts to facilitate expanded access affect these key principles, rendering expanded access a default option, allowing companies to charge for investigational drugs and gather data on its outcomes. These shifts may generate new ethical issues, including false hope, safety concerns and funding issues, which must be anticipated by physicians, pharmaceutical companies, payers and policymakers. CONCLUSION: Healthcare systems allow for the use of promising unapproved drugs in exceptional circumstances, but do not always assist patients with unmet medical needs in getting access. It is time to replace the current patchwork of practices with systems for expanded access in which criteria are clearly described, responsibilities are assigned and arrangements are made, so that patients will know what (not) to expect from expanded access.
Assuntos
Drogas em Investigação/uso terapêutico , Acessibilidade aos Serviços de Saúde/ética , Ensaios de Uso Compassivo/ética , Ensaios de Uso Compassivo/legislação & jurisprudência , Drogas em Investigação/economia , Acessibilidade aos Serviços de Saúde/legislação & jurisprudência , Humanos , Países BaixosRESUMO
BACKGROUND: This article proposes a retrospective analysis of a compassionate use (CU), using a case study of request for Avelumab for a patient suffering from Merkel Cell Carcinoma. The study is the result of a discussion within a Provincial Ethics Committee (EC) following the finding of a high number of requests for CU program. The primary objective of the study is to illustrate the specific ethical and clinical profiles that emerge from the compassionate use program (CUP) issue. The secondary goals are: a) to promote a moral reflection among physicians who require approval for the CUP and b) provide the basis for recommendations on how to request CUP. MAIN BODY: The instruments for carrying out the analysis of the case study and the discussion are as follows: Analysis of the audio-recording of the EC meeting regarding the selected Case study. In-depth discussion of topics that emerged during the meeting by means of administration of 5 semi-structured interviews with 2 doctors involved in the case (proposing physician and palliative physician) and with 3 components of the EC who played a major role in the EC internal discussion. CONCLUSIONS: In an exploration of emerging clinical and ethical issues, four primary themes arise: 1. efficacy, safety of the treatment and patient's quality of life; 2. clear, realistic, adequate communication; 3. right to hope; 4. simultaneous Palliative Care approach. The results of ethical analysis carried out concern two areas: 1) ethical profiles relating to the use of CUP; 2) the role of the EC concerning the compassionate use of drugs and the need to provide recommendations on how to request CUP. With the aim of implementing these conclusions, the provincial EC of Reggio Emilia chose to steer the request for drugs for compassionate use through recommendations for good clinical and ethical practice based on the following assumptions: 1) the "simultaneous care" approach must be preferred. Secondly, 2) the EC's assessment must be part of the decision-making process that the care team conducts before proposing compassionate use to the patient.
Assuntos
Temas Bioéticos , Ensaios de Uso Compassivo/ética , Tomada de Decisões/ética , Atenção à Saúde/ética , Comissão de Ética , Ética Médica , Cuidados Paliativos/ética , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Carcinoma de Célula de Merkel/tratamento farmacológico , Comunicação , Empatia , Análise Ética , Esperança , Humanos , Itália , Direitos do Paciente , Guias de Prática Clínica como Assunto , Qualidade de Vida , Estudos Retrospectivos , Assistência Terminal/éticaRESUMO
Introducción: el uso de anticuerpos monoclonales transformó el tratamiento de los linfomas no hodgkinianos. El Centro de Inmunología Molecular generó un anticuerpo anti-CD20 (CIMABior®) biosimilar del rituximab, que se ha caracterizado desde el punto de vista biológico, pero la seguridad y eficacia aún están en estudio. Objetivo: evaluar la seguridad y la respuesta al tratamiento con CIMABior ®, en pacientes con síndromes linfoproliferativos de células B tratados con intención compasiva. Métodos: estudio multicéntrico, exploratorio, con dos grupos de tratamiento (monoterapia o combinado con quimioterapia) no controlado, ni aleatorizado. Se incluyeron adultos con linfomas no hodgkinianos y leucemia linfocítica crónica, no elegibles para el ensayo clínico en ejecución con este producto. Se determinó la frecuencia de eventos adversos y se caracterizaron. La respuesta al tratamiento se definió como: remisión completa, remisión parcial, enfermedad estable o en progresión. Se calculó la tasa de respuesta objetiva (remisión completa más remisión parcial) con el intervalo de confianza al 95 por ciento, se evaluó la relación de algunas variables con la respuesta y se estimó la razón de Odss. Como medida de balance beneficio-riesgo se estimó el factor de Bayes. Resultados: los eventos adversos más frecuentes fueron: temblor (12,8 por ciento) y fiebre (10,3 por ciento). Los relacionados con el producto (43,4 por ciento) fueron leves o moderados y evolucionaron hacia la recuperación. No se informó muerte asociada directamente al tratamiento. Se constató respuesta objetiva global de 71,2 por ciento (59,6 por ciento de remisiones completas y 11,5 por ciento, parciales). La respuesta objetiva en el grupo de monoterapia fue de 66,7 por ciento y de 73,0 por ciento en el grupo de CIMABior® más quimioterapia, con remisiones completas de 46,7 por ciento y 64,9 por ciento, respectivamente. Conclusiones: el AcM CIMABior® es seguro, bien tolerado y se demostraron evidencias de efecto. El tratamiento aportó un beneficio clínico superior al riesgo de desarrollar algún evento adverso grave(AU)
Introduction : The use of monoclonal antibodies transformed the treatment of non-Hodgkin lymphomas. The Center of Molecular Immunology created an anti-CD20 monoclonal antibody (CIMABior®), biosimilar of rituximab, which has been characterized from a biological point of view, but the safety and effectiveness are still being studied. Objective: Evaluate the safety and response to treatment, in patients with B-cell malignancies with compassionate use of CIMABior®. Methods : A multicenter, exploratory, non-controlled, non-randomized study was conducted with two variants of treatments (monotherapy or combined with chemotherapy). Adults with non-Hodgkin lymphomas and chronic lymphocytic leukemia not eligible for clinical trial with this product were included. Frequency of adverse events was calculated and those were characterized. The response to treatment was defined as: complete response, partial response, stable disease or progressive disease. Overall response rate (complete plus partial remission) was calculated with 95 percent confidence interval. The relation of some variables with response was estimated per Odss ratio. As a measure of the benefit-risk balance, the Bayes factor was estimated. Results : The more frequent adverse events were: tremors (12.8 percent) and fever (10.3 percent). Those related to the product (43.4 percent) were minor and evolved to recovery. There were no deaths in reference to the treatment. An overall response of 71.2 percent was confirmed (59.6 percent complete remissions and 11.5 percent partial remission). The monotherapy group objective response was 66.7 percent and 73.0 percent in the CIMABior® plus chemotherapy group, with complete remissions of 46.7 percent and 64.9 percent respectively. Conclusions: The monoclonal antibodies CIMABor® is safe, well tolerated and evidences of its effectiveness was demonstrated. The treatment provided a superior clinical benefit to the risk of developing a severe adverse event(AU)
Assuntos
Humanos , Masculino , Feminino , Linfoma não Hodgkin/terapia , Leucemia de Células B/terapia , Resultado do Tratamento , Cuba , Ensaios de Uso Compassivo/ética , Citometria de Fluxo/métodos , Antineoplásicos Imunológicos/uso terapêutico , Anticorpos/uso terapêuticoAssuntos
Ensaios de Uso Compassivo/ética , Alocação de Recursos para a Atenção à Saúde/ética , Oligonucleotídeos/uso terapêutico , Seleção de Pacientes/ética , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Ética Médica , Humanos , Lactente , Terapias em Estudo/ética , Estados UnidosRESUMO
Patients with life-threatening disorders such as amyotrophic lateral sclerosis, for which only minimally effective medical therapies currently exist, often seek treatments not proven to be effective and not approved by regulatory agencies for use outside of experimental treatment trials. The expanded access (compassionate use) provisions of the US Food and Drug Administration (FDA) for access to such therapies are often perceived as being inadequate. In response, states have passed right-to-try laws designed to improve access to experimental therapies for patients willing to assume the risks associated with such treatments. This situation has resulted in conflicts between those who perceive access to such treatments as their right as autonomous individuals and those who believe that the principles of beneficence and nonmaleficence justify actions of physicians and regulators in controlling access to such treatments. A variety of factors also contribute to the inequitable distribution of such treatments. Better systems are needed to improve access to promising new treatments while protecting these vulnerable patients from the abuses associated with human research in the preregulatory era.