Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design

BACKGROUND Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question. METHODS/DESIGN We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials. DISCUSSION To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

Collective Referential Intentionality in the Semantics of Dialogue

The concept of a dialogue is considered in general terms from the standpoint of its referential presuppositions. The semantics of dialogue implies that dialogue participants must generally have a collective intentionality of agreed-upon references that is minimally sufficient for them to be able to disagree about other things, and ideally for outstanding disagreements to become clearer at successive stages of the dialogue. These points are detailed and illustrated in a fictional dialogue, in which precisely these kinds of referential confusions impede progress in shared understanding. It is only through a continuous exchange of question and answer in this dialogue case study that the meanings of key terms and anaphorical references are disambiguated, and a relevantly complete collective intentionality of shared meaning between dialogue participants is achieved. The importance of a minimally shared referential semantics for the terms entering into reasoning and argument in dialogue contexts broadly construed cannot be over-estimated. Where to draw the line between referential agreement and disagreement within any chosen dialogue, as participants work toward better mutual understanding in clearing up referential incongruities, is sometimes among the dialogue’s main points of dispute.

Law and science: risk assessment and risk management in the WTO agreement on the application of sanitary and phytosanitary measures

Assessing and managing risks relating to the consumption of food stuffs for humans and to the environment has been one of the most complex legal issues in WTO law, ever since the Agreement on Sanitary and Phytosanitary Measures was adopted at the end of the Uruguay Round and entered into force in 1995. The problem was expounded in a number of cases. Panels and the Appellate Body adopted different philosophies in interpreting the agreement and the basic concept of risk assessment as defined in Annex A para. 4 of the Agreement. Risk assessment entails fundamental question on law and science. Different interpretations reflect different underlying perceptions of science and its relationship to the law. The present thesis supported by the Swiss National Research Foundation undertakes an in-depth analysis of these underlying perceptions. The author expounds the essence and differences of positivism and relativism in philosophy and natural sciences. He clarifies the relationship of fundamental concepts such as risk, hazards and probability. This investigation is a remarkable effort on the part of lawyer keen to learn more about the fundamentals based upon which the law – often unconsciously – is operated by the legal profession and the trade community. Based upon these insights, he turns to a critical assessment of jurisprudence both of panels and the Appellate Body. Extensively referring and discussing the literature, he deconstructs findings and decisions in light of implied and assumed underlying philosophies and perceptions as to the relationship of law and science, in particular in the field of food standards. Finding that both positivism and relativism does not provide adequate answers, the author turns critical rationalism and applies the methodologies of falsification developed by Karl R. Popper. Critical rationalism allows combining discourse in science and law and helps preparing the ground for a new approach to risk assessment and risk management. Linking the problem to the doctrine of multilevel governance the author develops a theory allocating risk assessment to international for a while leaving the matter of risk management to national and democratically accountable government. While the author throughout the thesis questions the possibility of separating risk assessment and risk management, the thesis offers new avenues which may assist in structuring a complex and difficult problem