The principle of clinical equipoise requires that, aside from certain exceptional cases, second generation treatments ought to be tested against standard therapy. In violation of this principle, placebo-controlled trials (PCTs) continue to be used extensively in the development and licensure of second-generation treatments. This practice is typically justified by appeal to methodological arguments that purport to demonstrate that active-controlled trials (ACTs) are methodologically flawed. Foremost among these arguments is the so called assay sensitivity argument. In this paper, I take a (...) closer look at this argument. Following Duhem, I argue that all trials, placebo-controlled or not, rely on external information for their meaningful interpretation. Pending non-circular empirical evidence that we can trust the findings of PCTs to a greater degree than the findings of ACTs, I conclude that the assay sensitivity argument fails to demonstrate that placebo-controlled trials are preferable, methodologically or otherwise, to active-controlled trials. Contrary to the intentions of its authors, the fundamental lesson taught by the assay sensitivity argument is Duhemian: the validity of all clinical trials depends on external information. (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)

The IPAP Schizophrenia Algorithm was originally designed in the form of a flow chart to help physicians optimise the treatment of schizophrenic patients. We examined the current version from the perspective of recent work on terminologies and ontologies thereby drawing on the resources of Basic Formal Ontology, and this with the objective to make the algorithm appropriate for Semantic Web applications. We found that Basic Formal Ontology is a rich enough theory to represent all the entities involved and that applying (...) the theory to the IPAP schizophrenia algorithm results in a representation that can be used by software agents to perform monitoring and control in a referent tracking environment. (shrink)

In this paper, I offer one example of conceptual change. Specifically, I contend that the discovery that viruses could cause cancer represents an excellent example of branch jumping, one of Thagard’s nine forms of conceptual change. Prior to about 1960, cancer was generally regarded as a degenerative, chronic, non-infectious disease. Cancer causation was therefore usually held to be a gradual process of accumulating cellular damage, caused by relatively non-specific component causes, acting over long periods of time. Viral infections, on the (...) other hand, were generally understood to be acute processes, whereby single, specific and necessary causal agents acted alone to produce disease. However, during the 1960s and 1970s, a number of cancers were discovered to have an infectious aetiology. Of particular note were two—Burkitt’s lymphoma and cervical cancer—which I will discuss in detail later in this piece. Together, these discoveries led, in the short term, to a tentative aetiological reclassification of some types of cancer as infectious diseases and, in the longer term, to a full-blown reclassification of cancer as an aetiological disease branch in its own right. This process of reclassification forms the empirical basis for my concluding remarks on the influence of classification upon causation in medicine. Through this, I aim to demonstrate that conceptual change, far from being a purely abstract concern of the philosopher of science, is of substantial import to scientific practitioners. (shrink)

Method of Medicine, a systematic and comprehensive account of the principles of treating injury and disease and one of Galen's greatest and most influential works.

Before anaesthesia, surgery used to be agony. It’s hard to imagine that anyone could have been anything but pleased when painless surgery was introduced in the mid-19th century. And yet, although many welcomed anaesthesia, some did object. In Zurich, anaesthesia was even outlawed. “Pain is a natural and intended curse of the primal sin. Any attempt to do away with it must be wrong,” claimed the Zurich City Fathers. Painless delivery in childbirth was a particularly contentious issue. Some insisted that (...) “in sorrow thou shalt bring forth children” (Genesis 3:16). Others, like Doctor Charles Delucena Meigs (1792-1869), Professor of Obstetrics and Diseases of Women at Jefferson Medical College, believed that labour pains were “a most desirable, salutary and conservative manifestation of the life force.” There was even a belief, expressed in 1847 in The New York Journal of Medicine, that pain was vital to surgical procedure. (shrink)

In 2011 the Swiss government published a report on homeopathy. This report was commissioned following a 2009 referendum in which Swiss people decided that homeopathy and other alternative therapies should be covered by private medical insurance; before implementing this decision, the government wanted to establish whether homeopathy actually works. In February 2012 the report was published in English and was immediately proclaimed by proponents of homeopathy to be conclusive proof that homeopathy is effective. This paper analyses the report and concludes (...) that it is scientifically, logically and ethically flawed. Specifically, it contains no new evidence and misinterprets previously debunked studies; it creates a new standard of evidence in order to make homeopathy appear effective and attempts to discredit randomised controlled trials as the gold standard of evidence; and almost all the authors have conflicts of interest, despite their claim that none exist. If anything, the report proves that homeopaths are willing to distort the evidence in order to support their beliefs, and its authors appear to have violated the Swiss Academies of Arts and Sciences principles governing scientific integrity. (shrink)

If we are to develop efficient, reliable and secure means for sharing information across healthcare systems and organizations, then a careful analysis of human actions will be needed. To address this need, the HL7 organization has proposed its Reference Information Model (RIM), which is designed to provide a comprehensive representation of the entire domain of healthcare centered around the phenomenon of human action. Taking the Basic Formal Ontology as our starting point, we examine the RIM from an ontological point of (...) view, describing how it fails to provide a representation of the healthcare domain which would enjoy the sort of clarity, coherence, rigor and completeness that is claimed on its behalf. (shrink)

The value of any kind of data is greatly enhanced when it exists in a form that allows it to be integrated with other data. One approach to integration is through the annotation of multiple bodies of data using common controlled vocabularies or ‘ontologies’. Unfortunately, the very success of this approach has led to a proliferation of ontologies which itself creates obstacles to integration. The Open Biomedical Ontologies (OBO) consortium has set in train a strategy to overcome this problem. Existing (...) OBO ontologies, including the Gene Ontology, are undergoing a process of coordinated reform and new ontologies being created on the basis of an evolving set of shared principles governing ontology development. The result is an expanding family of ontologies designed to be interoperable, logically well-formed, and to incorporate accurate representations of biological reality. We describe the OBO Foundry initiative, and provide guidelines for those who might wish to become involved. (shrink)

The Health Level 7 Reference Information Model (HL7 RIM) is lauded by its authors as ‘the foundation of healthcare interoperability’. Yet even after some 10 years of development work, the RIM is still subject to a variety of logical and ontological flaws, which has placed severe obstacles in the way of those who are called upon to develop implementations. We offer evidence that these obstacles are insurmountable and that the time has come to abandon an unworkable paradigm.

An increasing number of drugs removed from the market because of unacceptable toxicity raises concerns regarding preapproval testing of drug safety. In the present paper it is postulated that the non-inferiority type of trial should be abandoned in favor of the superiority trial with active controls and less stringent (p<0.1, both for efficacy and toxicity) statistics. This approach will increase sensitivity of detection of drug-induced adverse effects at the expense of increasing false positive results regarding the difference in efficacy between (...) the tested and reference drug. Such a move will increase the protection of future patients. In addition, the proposed design is far more acceptable from the clinical (e.g. no need to specify the statistically expected “unimportant” number of deaths) and ethical points of view, as well as being favored by the strong incentive of involved parties. In the second part of this paper arguments are presented in favor of the hypothesis that placebo (still used in some superiority trials) does not induce adverse effects. The assertion that placebo may induce adverse effects is probably biased by the nature of the clinical experiment. Such a conclusion is supported by studies indicating that placebo-induced adverse effects are disease — and treatment — specific. The modification of clinical trials according to the proposed changes may increase the trials’ sensitivity at detecting adverse effects of drugs. (shrink)

Despite efforts from regulatory agencies (e.g. NIH, FDA), recent systematic reviews of randomised controlled trials (RCTs) show that top medical journals continue to publish trials without requiring authors to report details for readers to evaluate early stopping decisions carefully. This article presents a systematic way of modelling and simulating interim monitoring decisions of RCTs. By taking an approach that is both general and rigorous, the proposed framework models and evaluates early stopping decisions of RCTs based on a clear and consistent (...) set of criteria. The framework allows decision analysts to generate and quickly answer ‘what-if’ questions by simulating alternate trial scenarios. I illustrate the framework with a case study of an RCT that was stopped early due to harm. This was a trial of vitamin A supplement in relation to HIV transmission from mother-to-child through breastfeeding. (shrink)

Modern medicine has produced many successful theories concerning the causes of diseases. For example, we know that tuberculosis is caused by the bacterium Mycobacterium tuberculosis, and that scurvy is caused by a deficiency of vitamin C. This chapter discusses the nature of medical theories from the perspective of the philosophy, history, and psychology of science. I will review prominent philosophical accounts of what constitutes a scientific theory, and develop a new account of medical theories as representations of mechanisms that explain (...) disease. An account of the nature of medical theories should illuminate many aspects of the development and application of medical knowledge. Most importantly, it should contribute to understanding of medical explanation, both at the general level of causes of diseases and at the individual level of diagnosis of particular cases of a disease. Medical researchers seek to explain the causes of diseases such as tuberculosis, while physicians seek to identify diseases that explain symptoms such as fever. A medical theory such as the bacterial theory of tuberculosis provides good explanations at both the general and individual levels. The primary aim of this chapter is to show how these explanations work. A secondary aim is to show how an account of medical theories can shed light on other aspects of medical research and practice, including the nature of medical discovery, the process of evaluation of competing medical theories, and the ways in which effective treatments of disease depend on the development of good mechanistic theories about diseases. (shrink)

A biochemical pathway is a sequence of chemical reactions in a biological organism. Such pathways specify mechanisms that explain how cells carry out their major functions by means of molecules and reactions that produce regular changes. Many diseases can be explained by defects in pathways, and new treatments often involve finding drugs that correct those defects. This paper presents explanation schemas and treatment strategies that characterize how thinking about pathways contributes to biomedical discovery. It discusses the significance of pathways for (...) understanding the nature of diseases, explanations, and theories. (shrink)

It is argued that the common definition of diagnosis as the determination of the nature of a disease is misleading. Many diagnoses are not the names of disease entities. This finding reflects the integral relation of the diagnostic task to the rest of clinical reasoning. Diagnosis has no separate goal of its own, in particular it does not have the goal of determining the nature of a disease. Instead, diagnosis contributes to the general goals of clinical medicine. Any attempt to (...) model diagnostic reasoning abstracted from the rest of clinical reasoning will yield an inadequate representation of diagnosis. Such a distortion of medical reasoning will blind us to whatever implications an adequate epistemology of medicine may have for an understanding of the relation between theoretical and practical knowledge in other contexts. (shrink)