It is surely obvious that medicine, like any other rational activity, must be based on evidence. The interest is in the details: how exactly are the general principles of the logic of evidence to be applied in medicine? Focussing on the development, and current claims of the ‘Evidence-Based Medicine’ movement, this article raises a number of difficulties with the rationales that have been supplied in particular for the ‘evidence hierarchy’ and for the very special role within that hierarchy of randomized (...) controlled trials (and meta-analyses of the results of randomized controlled trials). The point is not at all to question the application of a scientific approach to evidence in medicine, but, on the contrary, to indicate a number of areas where philosophers of science can contribute to a proper implementation of exactly that scientific-evidential approach. (shrink)

Randomized Controlled Trials are currently the gold standard within evidence-based medicine. Usually, they are conducted as sequential trials allowing for monitoring for early signs of effectiveness or harm. However, evidence from early stopped trials is often charged with being biased towards implausibly large effects. To our mind, this skeptical attitude is unfounded and caused by the failure to perform appropriate conditioning in the statistical analysis of the evidence. We contend that a shift from unconditional hypothesis tests in the style of (...) Neyman and Pearson to conditional hypothesis tests gives a superior appreciation of the obtained evidence and significantly improves the practice of sequential medical trials, while staying firmly rooted in frequentist methodology. (shrink)

This paper argues that research on normative issues in the life sciences will benefit from a tighter integration of philosophy of science. We examine research on ethical, legal and social issues in the life sciences (“ELSI”) and discuss three illustrative examples of normative issues that arise in different areas of the life sciences. These examples show that important normative questions are highly dependent on epistemic issues which so far have not been addressed sufficiently in ELSI, RRI and related areas of (...) research. Accordingly, we argue for the integration of research on the epistemic aspects of the relevant areas of science into ELSI research to provide a better basis for addressing normative questions. (shrink)

A number of arguments have shown that randomization is not essential in experimental design. Scientific conclusions can be drawn on data from experimental designs that do not involve randomization. John Worrall has recently taken proponents of randomized studies to task for suggesting otherwise. In doing so, however, Worrall makes an additional claim: randomized interventional studies are epistemologically equivalent to observational studies, providing the experimental groups are comparable according to background knowledge. I argue against this claim. In the context of testing (...) the efficacy of drug therapies, well-designed interventional studies are epistemologically superior to well-designed observational studies because they have the capacity to avoid a type of selection bias. Although arguments for interventional studies are present in the medical literature, these arguments are too often presented as an argument for randomization. Randomization in interventional studies is defended on Bayesian grounds. (shrink)

In this essay, we defend the design of the Salk polio vaccine trial and try to put some limits on the role schemata should play in designing clinical research studies. Our presentation is structured as a response to de Freitas and Pietrobon who identified the CONSORT statement as a schema that would have, had it existed at the time, ruled out the design of the Salk polio vaccine trial of 1954 in favor of a completely randomized controlled clinical trial. We (...) argue that large-scale public health interventions often require evidence beyond simple efficacy, the limit of what an RCT can provide, and that the design actually adopted for the Salk trial represented a reasonable—albeit imperfect—compromise. This is of more than historical interest in that many contemporary studies are of the scale and scope to require a more pragmatic, rather than explanatory, approach to study design. (shrink)

The Belmont Report’s distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole (...) exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. (shrink)

What clinicians, biomedical scientists, and other health care professionals know as individuals or as groups and how they come to know and use knowledge are central concerns of medical epistemology. Activities associated with knowledge production and use are called epistemic practices. Such practices are considered in biomedical and clinical literatures, social sciences of medicine, philosophy of science and philosophy of medicine, and also in other nonmedical literatures. A host of different kinds of knowledge claims have been identified, each with different (...) uses and logics of justification. A general framework is needed to situate these diverse contributions in medical epistemology, so we can see how they fit together. But developing such a framework turns out to be quite tricky. In this survey, three possible frameworks are considered along with the difficulties associated with each of them. The essay concludes with a fourth framework, which considers any epistemology as part of a practice that is oriented toward overcoming errors that emerge in antecedently given practices where knowledge is developed and used. As medicine indirectly advances health by directly mitigating disease, so epistemology indirectly advances knowledge by directly mitigating error. (shrink)

Obesity is the focus of multiple lines of inquiry that have -- together and separately -- produced many deep insights into the physiology of weight gain and maintenance. We examine three such streams of research and show how they are oriented to obesity intervention through multilevel integrated approaches. The first research programme is concerned with the genetics and biochemistry of fat production, and it links metabolism, physiology, endocrinology and neurochemistry. The second account of obesity is developmental and draws together epigenetic (...) and environmental explanations that can be embedded in an evolutionary framework. The third line of research focuses on the role of gut microbes in the production of obesity, and how microbial activities interact with host genetics, development and metabolism. These interwoven explanatory strategies are driven by an orientation to intervention, both for experimental and therapeutic outcomes. We connect the integrative and intervention-oriented aspects of obesity research through a discussion of translation, broadening the concept to capture the dynamic, iterative processes of scientific practice and therapy development. This system-oriented analysis of obesity research expands the philosophical scrutiny of contemporary developments in the biosciences and biomedicine, and has the potential to enrich philosophy of science and medicine. (shrink)

Obesity is the focus of multiple lines of inquiry that have -- together and separately -- produced many deep insights into the physiology of weight gain and maintenance. We examine three such streams of research and show how they are oriented to obesity intervention through multilevel integrated approaches. The first research programme is concerned with the genetics and biochemistry of fat production, and it links metabolism, physiology, endocrinology and neurochemistry. The second account of obesity is developmental and draws together epigenetic (...) and environmental explanations that can be embedded in an evolutionary framework. The third line of research focuses on the role of gut microbes in the production of obesity, and how microbial activities interact with host genetics, development and metabolism. These interwoven explanatory strategies are driven by an orientation to intervention, both for experimental and therapeutic outcomes. We connect the integrative and intervention-oriented aspects of obesity research through a discussion of translation, broadening the concept to capture the dynamic, iterative processes of scientific practice and therapy development. This system-oriented analysis of obesity research expands the philosophical scrutiny of contemporary developments in the biosciences and biomedicine, and has the potential to enrich philosophy of science and medicine. (shrink)

Clinical research under the usual regulatory constraints may be difficult or even impossible in a public health emergency. Regulators must seek to strike a good balance in granting as wide therapeutic access to new drugs as possible at the same time as gathering sound evidence of safety and effectiveness. To inform current policy, I reexamine the philosophical rationale for restricting new medicines to clinical trials, at any stage and for any population of patients (which resides in the precautionary principle), to (...) show that its objective to protect public health, now or in the future, could soon be defeated in a pandemic. Providing wider therapeutic access and coordinating observations and natural experiments, including service delivery by cluster (wedged cluster trials), may provide such a balance. However, there are important questions of fairness to resolve before any such research can proceed. (shrink)

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)

I argue that difference-making should be a crucial element for evaluating the quality of evidence for mechanisms, especially with respect to the robustness of mechanisms, and that it should take central stage when it comes to the general role played by mechanisms in establishing causal claims in medicine. The difference- making of mechanisms should provide additional compelling reasons to accept the gist of Russo-Williamson thesis and include mechanisms in the protocols for Evidence- Based Medicine, as the EBM+ research group has (...) been advocating. (shrink)

(2013). What to Think of Canine Obesity? Emerging Challenges to Our Understanding of Human–Animal Health Relationships. Social Epistemology: Vol. 27, No. 1, pp. 90-104. doi: 10.1080/02691728.2012.760662.

The American Journal of Bioethics, Volume 11, Issue 9, Page 18-20, September 2011.

The American Journal of Bioethics, Volume 11, Issue 9, Page 20-21, September 2011.

Clinical equipoise has been proposed as an ethical principle relating uncertainty and moral leeway in clinical research. Although CE has traditionally been indicated as a necessary condition for a morally justified introduction of a new RCT, questions related to the interpretation of this principle remain woefully open. Recent proposals to rehabilitate CE have divided the bioethical community on its ethical merits. This paper presents a new argument that brings out the epistemological difficulties we encounter in justifying CE as a principle (...) to connect uncertainty and moral leeway in clinical ethics. The argument proposes, first, that the methodology of hypothetical retrospection is applicable to the RCT design and that it can accommodate uncertainty. As currently understood, however, HR should give up its reliance on the assumption of uncertainty transduction, because the latter assumes the principle of indifference, which does not accommodate uncertainty in the right way. The same principle is then seen to distort also the received interpretations of CE. (shrink)

Robert Truog describes the controversial randomized controlled trials (RCTs) of extracorporeal membrane oxygenation (ECMO) therapy in newborns. Because early results with ECMO indicated that it might be a great advance, saving many lives, Truog argues that ECMO should not have been tested using RCTs, but that a long-term, large-scale observational study of actual clinical practice should have been conducted instead. Central to Truog’s argument, however, is the idea that ECMO is an unusual case. Thus, it is an open question whether (...) Truog’s conclusions can be extended to other areas of medical research. In this paper, I look at epistemological and ethical issues arising in the care of patients with chronic diseases, using ECMO as a starting point. Both the similarities and the dissimilarities of these two cases highlight important issues in biomedical research and support a conclusion similar to Truog’s. Observational studies of clinical practice provide the best evidence to inform the treatment of patients with chronic disease. (shrink)

According to conventional wisdom, local gauge symmetry is not a symmetry of nature, but an artifact of how our theories represent nature. But a study of the so-called theta-vacuum appears to refute this view. The ground state of a quantized non-Abelian Yang-Mills gauge theory is characterized by a real-valued, dimensionless parameter theta—a fundamental new constant of nature. The structure of this vacuum state is often said to arise from a degeneracy of the vacuum of the corresponding classical theory, which degeneracy (...) allegedly arises from the fact that “large” (but not “small”) local gauge transformations connect physically distinct states of zero field energy. If that is right, then some local gauge transformations do generate empirical symmetries. In defending conventional wisdom against this challenge I hope to clarify the meaning of empirical symmetry while deepening our understanding of gauge transformations. I distinguish empirical from theoretical symmetries. Using Galileo’s ship and Faraday’s cube as illustrations, I say when an empirical symmetry is implied by a theoretical symmetry. I explain how the theta-vacuum arises, and how “large” gauge transformations differ from “small” ones. I then present two analogies from elementary quantum mechanics. By applying my analysis of the relation between empirical and theoretical symmetries, I show which analogy faithfully portrays the character of the vacuum state of a classical non-Abelian Yang-Mills gauge theory. The upshot is that “large” as well as “small” gauge transformations are purely formal symmetries of non-Abelian Yang-Mills gauge theories, whether classical or quantized. It is still worth distinguishing between these kinds of symmetries. An analysis of gauge within the constrained-Hamiltonian formalism yields the result that “large” gauge transformations should not be classified as gauge transformations; indeed, nor should “global” gauge transformations. In a theory in which boundary conditions are modeled dynamically, “global” gauge transformations may be associated with physical symmetries, corresponding to translations of these extra dynamical variables. Such translations are symmetries if and only if charge is conserved. But it is hard to argue that these symmetries are empirical, and in any case they do not correspond to any constant phase change in a quantum state. (shrink)

Hierarchies of evidence are an important and influential tool for appraising evidence in medicine. In recent years, hierarchies have been formally adopted by organizations including the Cochrane Collaboration [1], NICE [2,3], the WHO [4], the US Preventive Services Task Force [5], and the Australian NHMRC [6,7]. The development of such hierarchies has been regarded as a central part of Evidence-Based Medicine, a movement within healthcare which prioritises the use of epidemiological evidence such as that provided by Randomised Controlled Trials. Philosophical (...) work on the methodology of medicine has so far mostly focused on claims about the superiority of RCTs, and hence has largely neglected the questions of what hierarchies are, what assumptions they require, and how they affect clinical practice. This thesis shows that there is great variation in the hierarchies defended and in the interpretations they are, and can be, given. The interpretative assumptions made in using hierarchies are crucial to the content and defensibility of the underlying philosophical commitments concerning evidence and medical practice. Once this variation is been identified, it becomes clear that the little philosophical work that has been done so far affects only some hierarchies, under some interpretations. Modest interpretations offered by La Caze [11], conditional hierarchies like GRADE [12-14], and heuristic approaches such as that defended by Howick et al. [15,16] all survive previous philosophical criticism. This thesis extends previous criticisms by arguing that modest interpretations are so weak as to be unhelpful for clinical practice; that GRADE and similar conditional models omit clinically relevant information, such as information about variation in treatments’ effects and the causes of different responses to therapy; and that heuristic approaches lack the necessary empirical support. The conclusion is that hierarchies in general embed untenable philosophical assumptions: principally that information about average treatment effects backed by high-quality evidence can justify strong recommendations, and that the impact of evidence from individual studies can and should be appraised in isolation. Hierarchies are a poor basis for the application of evidence in clinical practice. The Evidence-Based Medicine movement should move beyond them and explore alternative tools for appraising the overall evidence for therapeutic claims. (shrink)