A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded

Le développement du bar homosexuel comme institution [1967]

This article is devoted to the gay bar scene in San Francisco in the 1960s. The author emphasizes police persecution and the structuring role of perpetual law enforcement interventions on community cohesion, sense of belonging, and the emergence of collective identity as an oppressed group. She shows that advances in rights were brought about by bar owners and that the struggle to maintain commercial establishments was constituted as a political issue, their existence being considered a collective right (that of assembly) under constant threat

Le développement du bar homosexuel comme institution [1967]

This article is devoted to the gay bar scene in San Francisco in the 1960s. The author emphasizes police persecution and the structuring role of perpetual law enforcement interventions on community cohesion, sense of belonging, and the emergence of collective identity as an oppressed group. She shows that advances in rights were brought about by bar owners and that the struggle to maintain commercial establishments was constituted as a political issue, their existence being considered a collective right (that of assembly) under constant threat

Reconsiderando gramsci: hegemonia no direito global Gramsci reconsidered: hegemony in global law

"Entre direitos iguais, a força decide", proferiu karl marx ao descrever a antinomia do direito em situações antagônicas das relações de produção capitalistas, em que "o direito [oferece resistência] ao direito" nesse ponto, marx aborda uma questão que se situa no centro de todas as teorias jurídicas críticas: que tipo de violência é velada por meio do mecanismo de ocultação denominado "direito"? Para responder a esta questão, tentar-se-á, a seguir, tornar a teoria da hegemonia de antonio gramsci e seu modelo de direito hegemônico produtivos para o campo da teoria do direito. Tal tarefa tem de lidar com a dupla dificuldade de que, por um lado, gramsci não foi um teórico do direito no sentido mais estrito, razão pela qual o potencial de sua teoria para uma análise do direito raramente foi utilizada. Por outro lado, sua abordagem só pode ser empregada por meio de uma crítica às restrições relacionadas a seu tempo. isso se aplica especialmente à sua concepção de economia como a base e a núcleo essencialista oculto (laclau; mouffe, 2001:69), assim como à sua ideia de 'classismo' sob a forma de um enfoque unilateral das classes, em que há preferencialmente mais de um "pluralismo de poder" e inúmeras lutas (litowitz, 2000: 536). Recuperar-se-á, consequentemente, argumentos-chave, ampliando-os pela utilização das recentes descobertas feitas pelas abordagens feminista e neomaterialista da teoria jurídica, bem como as análises de foucault acerca das tecnologias de poder. por fim, uma interpretação da teoria sistêmica das autonomizações comunicativas.<br>"Between equal rights, force decides," said karl marx, describing the antinomy of law in antagonistic situations of capitalist production relations, in which "law [stands] against law". he here addresses a question that lies at the centre of all critical legal theories: what violence is blurred in the medium of the concealment mechanism called 'law'? To answer this question, we shall attempt below to make antonio gramsci's hegemony theory and his model of a hegemonic law fertile for the theory of law. This task has to cope with the twofold difficulty that on the one hand gramsci was no theoretician of law in the narrower sense, which is why the potential of his theory for an analysis of law has only seldom been made use of. On the other, his approach can only be taken up through a critique of restrictions associated with his times. This applies particularly to his conception of the economy as the basis and as the concealed essentialist core (laclau/mouffe 2001: 69), as well as to his 'classism' in the form of a one-sided focusing on classes, where there is instead more of a "pluralism of power" and a multiplicity of struggles (litowitz 2000: 536). We shall accordingly regain key arguments by extending them using current findings of feminist and neo-materialist approaches to legal theory, as well as foucault's analyses of power technologies and finally a systems-theory interpretation of communicative autonomizations