Exploratory experiments are widely characterized as experiments that do not test hypotheses. Experiments that do test hypotheses are characterized as confirmatory experiments. Philosophers have pointed out that research programmes can be both confirmatory and exploratory. However, these definitions preclude single experiments being characterized as both exploratory and confirmatory; how can an experiment test and not test a hypothesis? Given the intuition that some experiments are exploratory, some are confirmatory, and some are both, a recharacterization of the relationship between exploratory and (...) confirmatory experimentation is needed. I discuss ‘phase IV’ trials to show what this recharacterization could look like. Phase IV trials can be exploratory and confirmatory insofar as they concurrently test hypotheses and explore for unforeseen phenomena. Even if it is uncontroversial that a single experiment can have multiple aims, the recharacterization of the relationship between exploratory and confirmatory experimentation is still required for these aims to be held together coherently. I offer an alternative characterization of the relationship between exploratory and confirmatory experimentation where the former remains a distinct kind of experimentation but is not characterized as non-hypothesis-testing. (shrink)

Worries about safety of approved drugs have pushed post registration research to become the fastest growing drug research phase. Until recently, phase IV studies were mainly conducted for marketing purposes and run much like a phase III trial—at institutions with experienced investigators and a list of inclusion and exclusion criteria. Innovative phase IV studies involve ordinary physicians in research naïve communities. This brings ethical issues familiar to medical research into clinical practice. As a consequence, individual physicians (...) are challenged to protect scientific integrity and to secure the ethical conduct of research. Several ethical issues need to be addressed in the process of developing a scientifically sound and ethically high principled practice of phase IV research.PHASE IVEssential to phase IV research is the focus on how drugs work in the real world. The research goal may be to explore a specific pharmacological effect, to establish the incidence of adverse reactions, or to determine the effects of long-term administration of a drug. They may also be designed to establish a new clinical indication for a drug.1 Subjects may or may not be randomised, and the studies typically involve large numbers of patient-subjects and physicians.Doubts concerning the scientific rigor and clinical value have put postmarketing research in a poor light. However, high quality phase IV research is badly needed to further pharmaceutical science. First, because it can provide reliable data on the effectiveness, safety and optimal use of a drug in treated populations.2 3 In pre-registration clinical trials , a pharmaceutical product is studied under unrealistic circumstances. Under-representation of women and elderly are common and the concomitant use of medicines is usually extremely restrictive in these trials.4 Second, phase IV can provide much needed data for evidence-based …. (shrink)

BackgroundIn this manuscript, we argue that within the context of phase IV, physician-researchers retain their fiduciary obligation to treat the patient-participants.DiscussionWe first clarify why the perspective that research ethics ought to be differentiated from clinical ethics is not applicable in phase IV, and therefore, why therapeutic orientation is most convivial in this phase. Next, assuming that ethics guidelines may be representative of common morality, we show that ethics guidelines see physician-researchers primarily as physicians and only secondarily as (...) researchers. We then elaborate on what a fiduciary obligation is and how some of the obligations are default duties. Lastly, we look at the fiduciary obligation of the physician-researcher in phase IV interventional trials.ConclusionThe fiduciary obligation to treat is not as easily waived as in earlier trials. Assuming the entwinement of research and practice in phase IV, physician-researchers, in collaboration with other researchers, investigators, and research ethics committees, should ensure that in terms of study design, methodology, and research practice, the therapeutic value of the research to the patient-participants is not diminished. (shrink)

The history of drug/vaccine development has included major advances guided primarily by risk/benefit analyses concerning the innovative agent, not by evidence-based clinical trials (Phase I–IV). Because the approval for new drugs is hindered under the present process, the system requires restructuring. The Phase I/II study period should be more flexible, using the “environment of knowledge” about the new agent, plus risk/benefit assessments. Phase III, as presently constructed, does not add new adverse events data, it provides a narrower (...) profile of drug efficacy than properly done Phase II studies, and placebo-controlled trials continue to raise unresolved ethical and social issues. Phase III studies should be abandoned for most drugs, and substituted with properly powered Phase II doseranging studies plus careful post-marketing surveillance. Phase III should be a penalty for poor drug development, not a regulatory requirement. (shrink)

A fundamentally new understanding of the classical electromagnetic interaction of a point charge and a magnetic dipole moment through order v 2 /c 2 is suggested. This relativistic analysis connects together hidden momentum in magnets, Solem's strange polarization of the classical hydrogen atom, and the Aharonov–Bohm phase shift. First we review the predictions following from the traditional particle-on-a-frictionless-rigid-ring model for a magnetic moment. This model, which is not relativistic to order v 2 /c 2 , does reveal a connection (...) between the electric field of the point charge and hidden momentum in the magnetic moment; however, the electric field back at the point charge due to the Faraday-induced changing magnetic moment is of order 1/c 4 and hence is negligible in a 1/c 2 analysis. Next we use a relativistic magnetic moment model consisting of many superimposed classical hydrogen atoms (and anti-atoms) interacting through the Darwin Lagrangian with an external charge but not with each other. The analysis of Solem regarding the strange polarization of the classical hydrogen atom is seen to give a fundamentally different mechanism for the electric field of the passing charge to change the magnetic moment. The changing magnetic moment leads to an electric force back at the point charge which (i) is of order 1/c 2 , (ii) depends upon the magnetic dipole moment, changing sign with the dipole moment, (iii) is odd in the charge q of the passing charge, and (iv) reverses sign for charges passing on opposite sides of the magnetic moment. Using the insight gained from this relativistic model and the analogy of a point charge outside a conductor, we suggest that a realistic multi-particle magnetic moment involves a changing magnetic moment which keeps the electromagnetic field momentum constant. This means also that the magnetic moment does not allow a significant shift in its internal center of energy. This criterion also implies that the Lorentz forces on the charged particle and on the point charge are equal and opposite and that the center of energy of each moves according to Newton's second law F=Ma where F is exactly the Lorentz force. Finally, we note that the results and suggestion given here are precisely what are needed to explain both the Aharonov–Bohm phase shift and the Aharonov–Casher phase shift as arising from classical electromagnetic forces. Such an explanation reinstates the traditional semiclassical connection between classical and quantum phenomena for magnetic moment systems. (shrink)

In this paper I attempt to trace the development of Gottfried Leibniz’s early thought on the status of the actually infinitely small in relation to the continuum. I argue that before he arrived at his mature interpretation of infinitesimals as fictions, he had advocated their existence as actually existing entities in the continuum. From among his early attempts on the continuum problem I distinguish four distinct phases in his interpretation of infinitesimals: (i) (1669) the continuum consists of assignable points separated (...) by unassignable gaps; (ii) (1670-71) the continuum is composed of an infinity of indivisible points, or parts smaller than any assignable, with no gaps between them; (iii) (1672-75) a continuous line is composed not of points but of infinitely many infinitesimal lines, each of which is divisible and proportional to a generating motion at an instant (conatus); (iv) (1676 onward) infinitesimals are fictitious entities, which may be used as compendia loquendi to abbreviate mathematical reasonings; they are justifiable in terms of finite quantities taken as arbitrarily small, in such a way that the resulting error is smaller than any pre-assigned margin. Thus according to this analysis Leibniz arrived at his interpretation of infinitesimals as fictions already in 1676, and not in the 1700's in response to the controversy between Nieuwentijt and Varignon, as is often believed. (shrink)

Largely due to the cultural and political shift of the Enlightenment, Western societies in the eighteenth century emerged from sectarian conflict and embraced a more religiously moderate path. In nine original essays, leading scholars ask whether exporting the Enlightenment solution is possible—or even desirable—today. Contributors begin by revisiting the Enlightenment's restructuring of the West, examining its ongoing encounters with Protestant and Catholic Christianity, Judaism, Islam, and Hinduism. While acknowledging the necessity of the Enlightenment emphasis on toleration and peaceful religious coexistence, (...) these scholars nevertheless have grave misgivings about the Enlightenment's spiritually thin secularism. The authors ultimately upend both the claim that the West's experience offers a ready-made template for the world to follow and the belief that the West's achievements are to be ignored, despised, or discarded. (shrink)

In developing the concept of assemblages, Gilles Deleuze draws at least some inspiration from Gilbert Simondon’s concept of information. While his acknowledgement of Simondon’s influence is almost entirely positive, Deleuze explicitly distances himself from the concept of information in order to avoid its link to the field of cybernetics. However, a Deleuzian informational ontology could instead be leveraged as an alternative to cybernetics. Drawing on the Spinozan link between the work of Deleuze and Simondon, it is possible to develop a (...) hybrid informational ontology. This system can not only offer a different approach to information, data and technology than the essentialist concept of information embraced by cybernetics, but also aligns well with recent research in the biological sciences that has disrupted a long-held concept of individuals as entirely separate and autonomous. Shifting away from the Platonic Form to a Deleuzian/simondonian in-formation furthers the post-human project aimed at understanding processes of subjectivation at multiple scales, including the micro and macro. (shrink)

Havstad and Smith (2019) argue that Lakatos’ “methodology of scientific research programs” (MSRP) is a promising philosophical framework for explaining the perceived empirical success of the hypothesis that birds are maniraptoran theropod dinosaurs, and the perceived empirical failures or stagnation of alternatives to that hypothesis. These conclusions are rejected: Havstad and Smith’s account of the alternative “research programs” inadequately characterizes criticism of the hypothesis that birds are maniraptoran theropods and they neither offer sufficient modifications to MSRP to correct its known (...) difficulties in deriving logically or empirically satisfactory criteria for the assessment and preferential selection of “research programs” from historiographical data, nor proposals to mitigate its tendency to promote confirmation bias and dogmatism. Independent flight loss, an important problem in systematic ornithology with implications for the origin of birds, provides a supplementary demonstration of how the application of MSRP in the present context would tend systematically to mislead investigations of the evolutionary history of birds by promoting an uncritical perspective. Given these difficulties, MSRP is an unacceptable philosophical framework for evaluating alternative hypotheses for the origin of birds. (shrink)

Juxtaposing the ecological insights of Arne Naess and Eihei Dōgen, Deane Curtin maintains that Dōgen’s metaphysical conception of sentience subsumes and corrects Naess’s ecologi­cal Self and its problem of limits. However, an alternative reading of Dōgen, one which deemphasizes the ontological status of the natural world in favor of how we epistemically view it, revitalizes Naess’s question of limits and enables us to reappropriate the problem as our problem. This line of thinking forces us to rethink how we relate to (...) the natural world. (shrink)

Commentators on the ethics of translational research find it morally problematic. Types of translational research are said to involve questionable benefits, special risks, additional barriers to informed consent, and severe conflicts of interest. Translational research conducted on the global poor is thought to exploit them and increase international disparities. Some commentators support especially stringent ethical review. However, such concerns are grounded only in pre-approval translational research (now called T1 ). Whether or not T1 has these features, translational research beyond approval (...) ( T2 : phase IV, health services, and implementation research) is unlikely to and, when conducted on the global poor, may support development. Therefore, insofar as T1 is morally problematic, and no independent objections to T2 exist, the ethics of translational research is diverse: while some translational research is problematic, some is not. Funding and oversight should reflect this diversity, and T2 should be encouraged, particularly when conducted among the global poor. (shrink)

The paper deals with visions of Kyiv in the writings of Russian and Ukrainian émigré writers during the interwar period. The city became a focal point of intensive intellectual debate whose participants regarded Kyiv not only as a place of a recent battleground but also as a sacral place and a highly symbolic image. Within the methodological framework of ethnic symbolism, this study attempts to explain how this physical/symbolic dichotomy was used to reinforce continuing claims for historical origin and cultural (...) heritage, thus serving the contemporary purpose of national identity and political legitimacy. It also deploys the concept of displacement as a complex process of negotiation between homeland and hostland within an émigré community — whose sense of loss and identity crisis creates additional impetus, though in different forms, for exploiting historical narratives. (shrink)

Thomas Szasz wrote over thirty books and several hundred articles, replete with mordant criticism of psychiatry. His works made him arguably one of the world's most recognized psychiatrists, albeit one of the most controversial. This book critically examines the legacy of a man who challenged the very concept of mental illness.