RESUMO
Most phase III trials in drug-resistant tuberculosis have either been underpowered to quantify differences in microbiological endpoints or have taken up to a decade to complete. Composite primary endpoints, dominated by differences in treatment discontinuation and regimen changes, may mask important differences in treatment failure and relapse. Although new regimens for drug-resistant tuberculosis appear very effective, resistance to new drugs is emerging rapidly. There is a need for shorter, safer and more tolerable regimens, including those active against bedaquiline-resistant tuberculosis. Transitioning from multiple regimen A versus regimen B trials to a single large phase III platform trial would accelerate the acquisition of robust estimates of relative efficacy and safety. Further efficiencies could be achieved by adopting modern adaptive platform designs. Collaboration among trialists, affected community representatives, funders and regulators is essential for developing such a phase III platform trial for drug-resistant tuberculosis treatment regimens.
La majorité des essais de phase III relatifs à la tuberculose pharmacorésistante soit n'étaient pas assez puissants pour quantifier les fluctuations au niveau des critères microbiologiques, soit étaient trop longs, se poursuivant parfois pendant dix ans. Les critères primaires composites, dominés par des différences dans l'interruption du traitement et les changements de schéma, pourraient dissimuler d'importantes variations en termes d'échec thérapeutique et de rechute. Bien que les nouveaux traitements contre la tuberculose pharmacorésistante semblent très efficaces, la résistance aux nouveaux médicaments évolue rapidement. Il est donc nécessaire d'opter pour des traitements plus courts, plus sûrs et mieux tolérés, y compris ceux actifs contre la tuberculose résistant à la bédaquiline. Délaisser la multitude d'essais opposant un schéma de traitement A à un schéma de traitement B pour se diriger vers un unique essai plateforme de phase III de grande envergure permettrait d'obtenir plus vite des estimations solides concernant l'innocuité et l'efficacité relative. En outre, adopter des modèles de plateforme modernes et adaptatifs contribuerait à de meilleures performances. Enfin, la collaboration entre investigateurs, représentants des communautés concernées, bailleurs de fonds et organismes de réglementation est essentielle à l'élaboration de ce type d'essai plateforme de phase III sur les traitements contre la tuberculose pharmacorésistante.
La mayoría de los ensayos en fase III sobre tuberculosis resistente a los fármacos no ha tenido la potencia suficiente para cuantificar diferencias en los criterios de valoración microbiológicos o ha tardado hasta una década en completarse. Los criterios de valoración principales compuestos, dominados por las diferencias en la interrupción del tratamiento y los cambios de régimen, pueden ocultar diferencias importantes en el fracaso del tratamiento y la recaída. Aunque los nuevos regímenes de tratamiento para la tuberculosis resistente a los fármacos parecen muy eficaces, la resistencia a los nuevos fármacos está apareciendo rápidamente. Se necesitan regímenes de tratamiento más cortos, seguros y tolerables, incluidos los activos contra la tuberculosis resistente a la bedaquilina. La transición de múltiples ensayos de régimen A frente a régimen B a un único gran ensayo de plataforma en fase III aceleraría la obtención de estimaciones sólidas de la eficacia y seguridad relativas. Podrían lograrse mayores eficiencias si se adoptaran diseños de plataforma adaptativos modernos. La colaboración entre los autores de los ensayos, los representantes de las comunidades afectadas, los financiadores y los reguladores es esencial para desarrollar un ensayo de plataforma en fase III de este tipo para los regímenes de tratamiento de la tuberculosis resistente a los fármacos.
Assuntos
Antituberculosos , Ensaios Clínicos Fase III como Assunto , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêuticoRESUMO
Tuberculosis drug development has stagnated for decades, so the recent availability of bedaquiline is welcome. Bedaquiline-containing regimens, now the first-line therapy recommended by WHO, have transformed the treatment of drug-resistant tuberculosis, offering safer and more effective oral treatment options. However, key obstacles need to be overcome to ensure global access and prevent the rapid development of resistance against this promising class of drugs. In this Personal View, building on an international workshop held in 2023, we evaluate the current evidence and suggest possible ways forward, recognising the tension between increasing use and slowing the rise of resistance. We also discuss problems in accessing bedaquiline-containing regimens, the potential widening of their use beyond drug-resistant tuberculosis, and lessons for utilising new drugs as they are developed.
RESUMO
This article considers how distanciation, understood as the active production of different forms of distance as a method of control, is used to manage people racialised and criminalised as migrants within the UK's hostile environment. Analysing different policies introduced under the hostile environment agenda, as well as the more recent New Plan for Immigration, we argue distanciation is a key tactic that shapes these policies and their implementation as well as offers us insight into changing forms of governing migration. Drawing on the analysis of a wide range of policy documents, the paper attends to different forms of distanciation used as a method of control within the UK's wider hostile environment and then presents the results of a case-study of how distanciation is mobilised within the English National Health Service, under the Migrant and Visitor Cost Recovery Programme in particular, which was introduced in 2014 to ensure the NHS receives 'a fair contribution' from people racialised as migrants. Addressing different forms of distanciation such as - spatial, legal and emotional - we argue that the lens of distance can offer insights into how detachment - increasing distance between different agents in immigration law and border enforcement is an intentional design to control empathy, solidarity and resistance. Tracing ways these forms of distanciation are designed into legislative and administrative measures helps us better understand how hostile environment policies work as well as locating agencies and possibilities of resistance within different spaces, agents and subjects of bordering.
RESUMO
OBJECTIVE: The NHS Health Check programme is a public screening and prevention initiative in England to detect early signs of cardiovascular ill health among healthy adults. We aimed to explore patient perspectives and experiences of a personalised Risk Report designed to improve cardiovascular risk communication in the NHS Health Check. DESIGN AND SETTING: This is a qualitative study with NHS Health Check attendees in three general practices in the London Borough of Newham. INTERVENTION AND PARTICIPANTS: A personalised Risk Report for the NHS Health Check was developed to improve communication of results and advice. The Risk Report was embedded in the electronic health record, printed with auto-filled results and used as a discussion aid during the NHS Health Check, and was a take-home record of information and advice on risk reduction for the attendees. 18 purposively sampled socially diverse participants took part in semistructured interviews, which were analysed thematically. RESULTS: For most participants, the NHS Health Check was an opportunity for reassurance and assessment, and the Risk Report was an enduring record that supported risk understanding, with impact beyond the individual. For a minority, ambivalence towards the Risk Report occurred in the context of attending for other reasons, and risk and lifestyle advice were not internalised or acted on. CONCLUSION: Our findings demonstrate the potential of a personalised Risk Report as a useful intervention in NHS Health Checks for enhancing patient understanding of cardiovascular risk and strategies for risk reduction. Also highlighted are the challenges that must be overcome to ensure transferability of these benefits to diverse patient groups. TRIAL REGISTRATION NUMBER: NCT02486913.