RESUMEN
Typhoidal Salmonella is a major global problem affecting more than 12 million people annually. Controlled human infection models (CHIMs) in high-resource settings have had an important role in accelerating the development of conjugate vaccines against Salmonella Typhi.The typhoidal Salmonella model has an established safety profile in over 2000 volunteers in high-income settings, and trial protocols, with modification, could be readily transferred to new study sites. To date, a typhoidal Salmonella CHIM has not been conducted in a low-resource setting, although it is being considered.Our article describes the challenges posed by a typhoidal Salmonella CHIM in the high-resource setting of Oxford and explores considerations for an endemic setting.Development of CHIMs in endemic settings is scientifically justifiable as it remains unclear whether findings from challenge studies performed in high-resource non-endemic settings can be extrapolated to endemic settings, where the burden of invasive Salmonella is highest. Volunteers are likely to differ across a range of important variables such as previous Salmonella exposure, diet, intestinal microbiota, and genetic profile. CHIMs in endemic settings arguably are ethically justifiable as affected communities are more likely to gain benefit from the study. Local training and research capacity may be bolstered.Safety was of primary importance in the Oxford model. Risk of harm to the individual was mitigated by careful inclusion and exclusion criteria; close monitoring with online diary and daily visits; 24/7 on-call staffing; and access to appropriate hospital facilities with capacity for in-patient admission. Risk of harm to the community was mitigated by exclusion of participants with contact with vulnerable persons; stringent hygiene and sanitation precautions; and demonstration of clearance of Salmonella infection from stool following antibiotic treatment.Safety measures should be more stringent in settings where health systems, transport networks, and sanitation are less robust.We compare the following issues between high- and low-resource settings: scientific justification, risk of harm to the individual and community, benefits to the individual and community, participant understanding, compensation, and regulatory requirements.We conclude that, with careful consideration of country-specific ethical and practical issues, a typhoidal Salmonella CHIM in an endemic setting is possible.
Asunto(s)
Recursos en Salud , Experimentación Humana Terapéutica/ética , Fiebre Tifoidea/terapia , Vacunas Tifoides-Paratifoides/administración & dosificación , Países Desarrollados/economía , Países en Desarrollo/economía , Voluntarios Sanos , Humanos , Proyectos de Investigación/legislación & jurisprudencia , Salmonella typhi/inmunología , Salmonella typhi/patogenicidad , Experimentación Humana Terapéutica/economía , Experimentación Humana Terapéutica/legislación & jurisprudencia , Fiebre Tifoidea/economía , Fiebre Tifoidea/microbiología , Vacunas Tifoides-Paratifoides/efectos adversos , Vacunas Tifoides-Paratifoides/economíaRESUMEN
This editorial introduces articles in this Special Issue, which are based on presentations given at the 2017 meeting of the Global Forum of Bioethics in Research meeting. The main themes presented at the meeting were the use of cluster randomized trials, stepped-wedge cluster randomized trials, and controlled human infection models in research conducted in low-resource settings. The editorial sets out which ethical issues may arise in the context of alternative trial designs and describes the articles in this issue that addresses some or more of the ethical issues, such as justification of the research design, risk-benefit evaluations and consent.
Asunto(s)
Recursos en Salud , Proyectos de Investigación/legislación & jurisprudencia , Experimentación Humana Terapéutica/ética , Voluntarios Sanos , Humanos , Experimentación Humana Terapéutica/economía , Experimentación Humana Terapéutica/legislación & jurisprudenciaAsunto(s)
Niños Huérfanos , Experimentación Humana Terapéutica/historia , Vacunación/historia , Niño , Niños Huérfanos/historia , Francia , Historia del Siglo XVIII , Historia del Siglo XIX , Humanos , Orfanatos/economía , Orfanatos/ética , Consentimiento Presumido/historia , Experimentación Humana Terapéutica/economía , Experimentación Humana Terapéutica/ética , Vacunación/economía , Vacunación/éticaRESUMEN
No disponible
Asunto(s)
Femenino , Humanos , Masculino , Órganos Bioartificiales/ética , Órganos Bioartificiales/psicología , Experimentación Humana Terapéutica/ética , Trasplante de Órganos/ética , Trasplante de Órganos/métodos , Preparaciones Farmacéuticas , Ovario/anomalías , Hígado/lesiones , Órganos Bioartificiales/tendencias , Órganos Bioartificiales , Experimentación Humana Terapéutica/economía , Trasplante de Órganos , Trasplante de Órganos/instrumentación , Preparaciones Farmacéuticas/administración & dosificación , Ovario/citología , Hígado/patologíaAsunto(s)
Ensayos Clínicos como Asunto/ética , Oryza/genética , Plantas Modificadas Genéticamente , Experimentación Humana Terapéutica/ética , Deficiencia de Vitamina A/dietoterapia , Pueblo Asiatico , Niño , China , Ensayos Clínicos como Asunto/economía , Humanos , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)/economía , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)/ética , Experimentación Humana Terapéutica/economía , Estados UnidosAsunto(s)
Investigaciones con Embriones/economía , Investigaciones con Embriones/legislación & jurisprudencia , Células Madre Embrionarias , Financiación Gubernamental , Formulación de Políticas , Política Pública , Apoyo a la Investigación como Asunto , Investigaciones con Embriones/ética , Comités de Ética en Investigación , Gobierno Federal , Financiación Gubernamental/historia , Financiación Gubernamental/tendencias , Historia del Siglo XX , Historia del Siglo XXI , Humanos , National Institutes of Health (U.S.) , Religión , Sujetos de Investigación/legislación & jurisprudencia , Apoyo a la Investigación como Asunto/historia , Apoyo a la Investigación como Asunto/tendencias , Experimentación Humana Terapéutica/economía , Experimentación Humana Terapéutica/legislación & jurisprudencia , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Research participants' views about investigator financial interests were explored. Reactions ranged from concern to acceptance, indifference, and even encouragement. Although most wanted such information, some said it did not matter, was private, or was burdensome, and other factors were more important to research decisions. Very few said it would affect their research decisions, and many assumed that institutions managed potential conflicts of interest. Although disclosure of investigator financial interest information to research participants is often recommended, its usefulness is limited, especially when participation is desired because of illness.
Asunto(s)
Actitud Frente a la Salud , Investigación Biomédica/economía , Conflicto de Intereses/economía , Toma de Decisiones , Revelación/ética , Comités de Ética en Investigación/economía , Sujetos de Investigación/psicología , Apoyo a la Investigación como Asunto , Investigación Biomédica/ética , Comités de Ética en Investigación/ética , Humanos , Consentimiento Informado , Entrevistas como Asunto , Investigación Cualitativa , Experimentación Humana Terapéutica/economía , Experimentación Humana Terapéutica/ética , Confianza , Estados UnidosAsunto(s)
Diseño de Fármacos , Neoplasias/terapia , Animales , Aprobación de Drogas/economía , Aprobación de Drogas/legislación & jurisprudencia , Humanos , Medición de Riesgo , Experimentación Humana Terapéutica/economía , Experimentación Humana Terapéutica/ética , Experimentación Humana Terapéutica/legislación & jurisprudencia , Estados Unidos , United States Food and Drug AdministrationAsunto(s)
Clonación de Organismos/ética , Investigaciones con Embriones/ética , Animales , Actitud del Personal de Salud , Discusiones Bioéticas , Clonación Molecular , Clonación de Organismos/economía , Clonación de Organismos/tendencias , Investigaciones con Embriones/economía , Expresión Génica , Humanos , Experimentación Humana Terapéutica/economía , Experimentación Humana Terapéutica/éticaAsunto(s)
Investigación Biomédica , Ensayos Clínicos como Asunto , Investigación Biomédica/economía , Educación de Postgrado , Humanos , National Institutes of Health (U.S.) , Apoyo a la Investigación como Asunto , Salarios y Beneficios , Experimentación Humana Terapéutica/economía , Apoyo a la Formación Profesional , Estados UnidosAsunto(s)
Ensayos Clínicos como Asunto/economía , Cobertura del Seguro , Medicare , Neumonectomía/economía , Política Pública , Enfisema Pulmonar/cirugía , Resultado del Tratamiento , Anciano , Humanos , Cobertura del Seguro/legislación & jurisprudencia , Medicare/economía , Pacientes , Médicos , Enfisema Pulmonar/economía , Negativa a Participar , Experimentación Humana Terapéutica/economía , Estados UnidosRESUMEN
The clinical trial of the AbioCor artificial heart, initiated in July 2001 and still in process, has taken place within a matrix of social and cultural patterns that are both "old" and new. The old patterns--those that have accompanied previous clinical trials of other vital artificial organs and transplantation in the United States--include "experiment perilous," and courage, heroism, and pioneering themes; "right stuff" motifs; "Americana" symbols; allusions to the meaning of the human heart; connections with a for-profit corporation; and the occurrence of moratoriums. New patterns--those more particular and distinctive to the AbioCor trial--involve the restrictions imposed on releasing information about the post-operative clinical status of the implant recipients; the quasi-institutionalization of a patient advocacy system to represent patient-subjects and their families; and the "crises of success" that were encountered when several of the AbioCor recipients survived longer than expected. In certain instances, old and new patterns have been combined--for example, in some of the idiosyncratic features of the AbioCor-associated lawsuit that has resulted in part from the problem of the "therapeutic misconception," the belief that an experimental intervention is actually intended to be a treatment.
Asunto(s)
Actitud Frente a la Salud , Ensayos Clínicos como Asunto , Comercio/organización & administración , Cultura , Corazón Artificial , Implantes Experimentales , Experimentación Humana Terapéutica , Ensayos Clínicos como Asunto/economía , Comercio/economía , Comercio/ética , Formularios de Consentimiento , Financiación Gubernamental , Corazón Artificial/efectos adversos , Corazón Artificial/economía , Humanos , Implantes Experimentales/efectos adversos , Implantes Experimentales/economía , Masculino , National Institutes of Health (U.S.) , Evaluación de Resultado en la Atención de Salud , Alta del Paciente , Enfermo Terminal , Experimentación Humana Terapéutica/economía , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Should patients in a randomized, pragmatic health economics trial be allowed to switch therapy in mid-trial to that provided in the other arm? Specifically, should patients in the treatment arm (T) be allowed to switch to the therapy of the comparator arm (C) if they need a change of therapy--that is, should TC switches be allowed? Also, should patients in the comparator arm be allowed to switch to the therapy of the treatment arm if they need changes of therapy--should CT switches be allowed? This is a nontrivial issue in study design that has been debated in the clinical trials literature and is currently being handled inconsistently in the health economics literature. In this article, the authors argue that TC switches should always be allowed and that CT switches should be allowed or not depending on the economic question. They further argue that the most common economic question is one that would lead to CT switches not being allowed.
Asunto(s)
Análisis Costo-Beneficio , Ensayos Clínicos Controlados Aleatorios como Asunto , Experimentación Humana Terapéutica , Canadá , Estudios Cruzados , Evaluación de Medicamentos , Humanos , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Experimentación Humana Terapéutica/economíaRESUMEN
A predominant ethical view holds that physician-investigators should conduct their research with therapeutic intent. And since a physician offering a therapy wouldn't prescribe second-rate treatments, the experimental intervention and the best proven therapy should appear equally effective. "Clinical equipoise" is necessary. But this perspective is flawed. The ethics of research and of therapy are fundamentally different, and clinical equipoise should be abandoned.
Asunto(s)
Conflicto de Intereses , Ética Médica , Ética en Investigación , Obligaciones Morales , Ensayos Clínicos Controlados Aleatorios como Asunto/ética , Experimentación Humana Terapéutica/ética , Beneficencia , Revelación/ética , Apoyo Financiero/ética , Humanos , Consentimiento Informado/ética , Apoyo a la Investigación como Asunto/economía , Apoyo a la Investigación como Asunto/ética , Experimentación Humana Terapéutica/economía , IncertidumbreRESUMEN
OBJECTIVE: To explore the opinions of unpaid healthy volunteers on the payment of research subjects. DESIGN: Prospective cohort. SETTING: Southern Alberta, Canada. PARTICIPANTS: Medically eligible persons responding to recruiting advertisements for a randomised vaccine trial were invited to take part in a study of informed consent at the point at which they formally consented or refused trial participation. Of 72 invited, 67 (62 trial consenters, 5 trial refusers) returned questionnaires at baseline and 54 at follow-up. OUTCOME MEASURES: Proportions of persons who agreed or disagreed with three close-ended statements on the payment of research subjects; themes and categories identified by content analysis of responses to an open-ended question. RESULTS: A minority (43.3%) agreed with paying either patient or healthy volunteer participants. Opinions did not change over time. Participants' comments addressed: benefits and drawbacks to research participation; benefits and drawbacks to paying research participants; conditions under which payment of research subjects would be acceptable, and the nature of acceptable recognition. Acceptable conditions were to improve problematic recruitment, to reimburse costs, and to recognise participants, particularly for their time investment. Both non-monetary and monetary recognition of volunteers were thought to be appropriate. CONCLUSIONS: Most unpaid volunteers disagreed with paying research participants. The themes arising from their comments are similar to those that have been raised by ethicists and suggest that recognising the time and effort of participants should receive greater emphasis than presently occurs.