Objective: Ethical guidelines are designed to ensure benefits, protection and respect of participants in clinical research. Clinical trials must now be registered on open-access databases and provide details on ethical considerations. This systematic survey aimed to determine the extent to which recently registered clinical trials report the use of standard of care and post-trial obligations in trial registries, and whether trial characteristics vary according to setting. Methods: We selected global randomized trials registered on http://www.clinicaltrials.gov and http://www.controlled-trials.com. We searched for intervention (...) trials of HIV/AIDS, malaria, and tuberculosis from 9 October 2004, the date of the most recent version of the Helsinki Declaration, to 10 April 2007. Results: We collected data from 312 trials. Fifty-eight percent (58%, 95% CI = 53 to 64) of trial protocols report informed consent. Fifty-eight percent (58%, 95% CI = 53 to 64) of trials report active controls. Almost no trials (1%, 95% CI = 0.5 to 3) mention post-trial provisions. Most trials measure surrogate outcomes. Twenty percent (20%, 95% CI = 16 to 25) of trials measure patient-important outcomes, such as death; and the odds that these outcomes are in a low income country are five times greater than for a developed country (odds ratio (OR) 5.03, 95% CI = 2.70 to 9.35, p = < 0.001). Pharmaceutical companies are involved in 28% (CI = 23 to 33) of trials and measure surrogate outcomes more often than nonpharmaceutical companies (OR 2.45, 95% CI = 1.18 to 5.09, p = 0.31). Conclusion: We found a large discrepancy in the quality of reporting and approaches used in trials in developing settings compared to wealthier settings. (shrink)
In this commentary, we highlight a difficulty for metric navigation arising from recent data with grid and place cells: the integration of piecemeal representations of space in environments with repeated boundaries. Put simply, it is unclear how place and grid cells might provide a global representation of distance when their fields appear to represent repeated boundaries within an environment. One implication of this is that the capacity for spatial inferences may be limited.
This volume addresses a wide variety of moral concerns regarding slavery as an institutionalized social practice. By considering the slave's critical appropriation of the natural rights doctrine, the ambiguous implications of various notions of consent and liberty are examined. The authors assume that, although slavery is undoubtedly an evil social practice, its moral assessment stands in need of a more nuanced treatment. They address the question of what is wrong with slavery by critically examining, and in some cases endorsing, certain (...) principles derived from communitarianism, paternalism, utilitarianism, and jurisprudence. (shrink)
My commentators point to respects in which the picture provided in Reference without Referents is incomplete. The picture provided no account of how sentences constructed from intensional verbs can be true when one of the referring expressions fails to refer. And it gave an incomplete, and possibly misleading, account of how to understand certain serious uses of fictional names, as in "Anna Karenina is more intelligent than Emma Bovary" and "Anna Karenina does not exist". In the present response, I (...) indicate how I would now wish to make good these deficiencies. The truth of sentences constructed from intensional verbs can be explained in terms of the truth of sentences that are unproblematic for RWR, for example, sentences dominated by operators expressing propositional attitudes. Reflection on the way in which we can temporarily accept commitments we do not in fact share leads to a more nuanced account of serious uses of fictional names, some of which manifest precisely such a temporary acceptance. /// Mis comentadores señalan aspectos en los que la propuesta de Reference without Referents es incompleta: no ofrecía una explicación de cómo oraciones construidas con verbos intensionales pueden ser verdaderas cuando una de las expresiones referenciales no refiere; y dio una explicación incompleta, y quizás engañosa, de cómo entender ciertos usos serios de nombres de ficción como en "Anna Karenina es más inteligente que Emma Bovary" y "Anna Karenina no existe". En esta respuesta indico cómo quiero ahora subsanar estas deficiencias. La verdad de las oraciones construidas con verbos intensionales puede explicarse en términos de la verdad de oraciones que no son problemáticas para la explicación de Reference without Referents, por ejemplo, oraciones dominadas por operadores que expresan actitudes proposicionales. Una reflexión sobre cómo podemos aceptar temporalmente compromisos que de hecho no compartimos conduce a una explicación más matizada de los usos serios de los nombres de ficción, algunos de los cuales manifiestan precisamente esa aceptación temporal. (shrink)
Aim: To examine how physicians’ life stances affect their attitudes to end-of-life decisions and their actual end-of-life decision-making.Methods: Practising physicians from various specialties involved in the care of dying patients in Belgium, Denmark, The Netherlands, Sweden, Switzerland and Australia received structured questionnaires on end-of-life care, which included questions about their life stance. Response rates ranged from 53% in Australia to 68% in Denmark. General attitudes, intended behaviour with respect to two hypothetical patients, and actual behaviour were compared between all large (...) life-stance groups in each country.Results: Only small differences in life stance were found in all countries in general attitudes and intended and actual behaviour with regard to various end-of-life decisions. However, with regard to the administration of drugs explicitly intended to hasten the patient’s death , physicians with specific religious affiliations had significantly less accepting attitudes, and less willingness to perform it, than non-religious physicians. They had also actually performed PAD less often. However, in most countries, both Catholics and Protestants reported ever having made such a decision.Discussion: The results suggest that religious teachings influence to some extent end-of-life decision-making, but are certainly not blankly accepted by physicians, especially when dealing with real patients and circumstances. Physicians seem to embrace religious belief in a non-imperative way, allowing adaptation to particular situations. (shrink)
Objectives To evaluate whether the requirement of “minimal risk and burden” for paediatric research without direct benefit to the subjects compromises the ability to obtain data necessary for improving paediatric care. To provide evidence-based reflections on the EU recommendation that allows for a higher level of risk. Design and setting Systematic analysis of the approval/rejection decisions made by the Dutch Central Committee on Research involving Human Subjects (CCMO). Review methods The analysis included 165 proposals for paediatric research without direct benefit (...) that were reviewed by the CCMO between January, 2000, and July, 2007. A separate, in-depth analysis of all drug studies included 18 early phase drug studies and nine other drug studies without direct benefit. Results 11 out of 165 studies were definitively rejected because the CCMO did not regard the risk and/or burden to be minimal. In three of these 11 cases (including two early phase drug studies) the requirement of minimal risk and burden was cited as the only reason for rejection. Four other early phase drug studies also involved risks and/or burdens that were not regarded to be minimal but were nevertheless approved. Conclusions The requirement of minimal risk and burden, aiming to protect research subjects, occasionally leads to rejection of protocols. Early phase drug studies relatively often do not comply with the requirement. Committees may find ways to approve important studies that formally should be rejected, but that is not a desirable solution. The regulatory framework should be revised to make such occasional exceptions to the requirement legitimate and transparent. (shrink)