Alexander Mebius

Proponents of evidence-based medicine have argued convincingly for applying this scientific method to medicine. However, the current methodological framework of the EBM movement has recently been called into question, especially in epidemiology and the philosophy of science. The debate has focused on whether the methodology of randomized controlled trials provides the best evidence available. This paper attempts to shift the focus of the debate by arguing that clinical reasoning involves a patchwork of evidential approaches and that the emphasis on evidence hierarchies of methodology fails to lend credence to the common practice of corroboration in medicine. I argue that the strength of evidence lies in the evidence itself, and not the methodology used to obtain that evidence. Ultimately, when it comes to evaluating the effectiveness of medical interventions, it is the evidence obtained from the methodology rather than the methodology that should establish the strength of the evidence.

Since its introduction just over two decades ago, evidence-based medicine (EBM) has come to dominate medical practice, teaching, and policy. There are a growing number of textbooks, journals, and websites dedicated to EBM research, teaching, and evidence dissemination. EBM was most recently defined as a method that integrates best research evidence with clinical expertise and patient values and circumstances in the treatment of patients. There have been debates throughout the early 21st century about what counts as good research evidence between EBM proponents and philosophical critics and even within the EBM community itself. Similar controversy arises about the relative worth of patient values and clinical expertise (and how these can be integrated). EBM has also evolved in ways that have come under scrutiny. Specifically, policymakers have used EBM research methodology to increase the relative importance of clinical guidelines that some clinicians have argued are tyrannical. Philosophers have addressed all of these controversies, and with very few exceptions have been critical of EBM. In addition most philosophical attention has been on the epistemic role of Randomization and evidence hierarchies, with relatively little attention being paid to the role of Diagnosis, expertise, patient values, and Systematic Reviews within EBM.

Much contemporary debate on the nature of mechanisms centers on the issue of modulating negative causes. One type of negative causability, which I refer to as “causation by absence,” appears difficult to incorporate into modern accounts of mechanistic explanation. This paper argues that a recent attempt to resolve this problem, proposed by Benjamin Barros, requires improvement as it overlooks the fact that not all absences qualify as sources of mechanism failure. I suggest that there are a number of additional types of effects caused by absences that need to be incorporated to account for the diversity of causal connections in the biological sciences. Furthermore, it is argued that recognizing natural variability in mechanisms, such as attenuation, leads to some interesting line-drawing issues for contemporary philosophy of mechanisms.

Introduction Current treatments for pain have limited benefits and worrying side effects. Some studies suggest that pain is reduced when clinicians deliver positive messages. However, the effects of positive messages are heterogeneous and have not been subject to meta-analysis. We aimed to estimate the efficacy of positive messages for pain reduction. Methods We included randomized trials of the effects of positive messages in a subset of the studies included in a recent systematic review of context factors for treating pain. Several electronic databases were searched. Reference lists of relevant studies were also searched. Two authors independently undertook study selection, data extraction, risk of bias assessment, and analyses. Our primary outcome measures were differences in patient- or observer-reported pain between groups who were given positive messages and those who were not. Results Of the 16 randomized trials (1703 patients) that met the inclusion criteria, 12 trials had sufficient data for meta-analysis. The pooled standardized effect size was −0.31 (95% confidence interval [CI] −0.61 to −0.01, p = 0.04, I2 = 82%). The effect size remained positive but not statistically significant after we excluded studies considered to have a high risk of bias (standard effect size −0.17, 95% CI −0.54 to 0.19, P = 0.36, I2 = 84%). Conclusion Care of patients with chronic or acute pain may be enhanced when clinicians deliver positive messages about possible clinical outcomes. However, we have identified several limitations of the present study that suggest caution when interpreting the results. We recommend further high-quality studies to confirm (or falsify) our result. FUNDING Alexander Mebius research has been funded through the ERC grant "Philosophy of Pharmacology: Safety, Statistical Standards, and Evidence Amalgamation" (GA: 639276)

Background Healthcare is predicated on the use of biotechnology and medical technology, both of which are indispensable in diagnosis, treatment, and most aspects of patient care. It is therefore imperative that justifications for use of new technologies are appropriate, with the technologies working as advertised. In this paper, I consider philosophical accounts of how such justifications are made. Methods Critical philosophical reflection and analysis. Results I propose that justification in many prominent accounts is based on the designer’s professional experience and on expert testimony. I argue, however, that professional designers are not in a position to justify a new biotechnology or medical device if the justification is based on testimony or past experience of presumably similar technologies. I argue (1) that similarity judgments offered by instantaneous experts cannot be viewed as contributing (epistemically) to evidential justification of new and unproven technologies; and (2) that designers and manufacturers cannot endorse a technology’s effective function in a patient-care context until it has been successfully used in that context. Conclusion I show that an expert’s past professional experiences can never predict or justify the impact of a novel technology on human health. This is because any new technology leads to the introduction of new mechanisms with unprecedented functions. The new technology therefore needs to be studied in situ and justified as a newly created mechanism within the relevant healthcare setting. Ultimately, justifications of this type rely on the scientific community and society engaging in repeated experimentation and observation of the technology, and confirming its successful use.

This thesis examines philosophical controversies surrounding the evaluation of medical treatments, with a focus on the evidential roles of randomised trials and mechanisms in Evidence-Based Medicine. Current 'best practice' usually involves excluding non-randomised trial evidence from systematic reviews in cases where randomised trials are available for inclusion in the reviews. The first paper challenges this practice and evaluates whether adding of evidence from non-randomised trials might improve the quality and precision of some systematic reviews. The second paper compares the alleged methodological benefits of randomised trials over observational studies for investigating treatment benefits. It suggests that claims about the superiority of well-conducted randomised controlled trials over well-conducted observational studies are justified, especially when results from the two methods are contradictory. The third paper argues that postulating the unpredictability paradox in systematic reviews when no detectable empirical differences can be found requires further justification. The fourth paper examines the problem of absence causation in the context of explaining causal mechanisms and argues that a recent solution is incomplete and requires further justification. Solving the problem by describing absences as causes of 'mechanism failure' fails to take into account the effects of absences that lead to vacillating levels of mechanism functionality. The fifth paper criticises literature that has emphasised functioning versus 'broken' or 'non-functioning' mechanisms emphasising that many diseases result from increased or decreased mechanism function, rather than complete loss of function. Mechanistic explanations must account for differences in the effectiveness of performed functions, yet current philosophical mechanistic explanations do not achieve this. The last paper argues that the standard of evidence embodied in the ICE theory of technological function is too permissive for evaluating whether the proposed functions of medical technologies have been adequately assessed and correctly ascribed. It argues that high-quality evidence from clinical studies is necessary to justify functional ascriptions to health care technologies.

Modern health care relies extensively on the use of technologies for assessing and treating patients, so it is important to be certain that health care technologies perform their professed functions in an effective and safe manner. Philosophers of technology have developed methods to assign and evaluate the functions of technological products, the major elements of which are described in the ICE theory. This paper questions whether the standard of evidence advocated by the ICE theory is adequate for ascribing and assessing technologies employed in health care. The paper proposes that the general problem with the standard of evidence embodied in the ICE theory is too permissive for assessing medical technologies, in that it does not take into account the relative benefit and harm of medical technologies in ensuring safe functional performance in patients. The paper illustrates how evidence-based medicine has demonstrated the value of clinical research methods, including observational studies, randomized and non-randomized clinical trials, and formal techniques, such as meta-analysis, to measure therapeutic effectiveness. I argue, therefore, that evidence from clinical research studies should take precedence over the testimonial evidence and other types of non-clinical evidence, in providing justification for health technologies.

Financial modelling is an essential tool for studying the possibility of financial transactions. This paper argues that financial models are conventional tools widely used in formulating and establishing possibility claims about a prospective investment transaction, from a set of governing possibility assumptions. What is distinctive about financial models is that they articulate how a transaction possibly could occur in a non-actual investment scenario given a limited base of possibility conditions assumed in the model. For this reason, it is argued that the epistemic contribution of financial models is that of enabling the model users to envision exactly how a prospective investment could be achieved in various ways through a detailed understanding of the available transaction mechanisms. Thus, financial models provide information about the possibility of an investment scenario by showing how a specific transaction mechanism could result from a small set of initial possibility conditions assumed in the model.

Increasing philosophical attention is being directed to the rapidly growing discipline of evidence-based medicine. Philosophical discussions of EBM, however, remain narrowly focused on randomization, mechanisms, and the sociology of EBM. Other aspects of EBM have been all but ignored, including the nature of clinical reasoning and the question of whether it can be standardized; the application of EBM principles to the logic, value, and ethics of diagnosis and prognosis; evidence synthesis ; and the nature and ethics of placebo controls. Philosophical analysis in each of these areas has the potential to enhance the discussion of EBM methodology and practice.

Much contemporary debate on the nature of mechanisms centers on the issue of modulating negative causes. One type of negative causability, which I refer to as "causation by absence," appears difficult to incorporate into modern accounts of mechanistic explanation. This paper argues that a recent attempt to resolve this problem, proposed by Benjamin Barros, requires improvement as it overlooks the fact that not all absences qualify as sources of mechanism failure. I suggest that there are a number of additional types of effects caused by absences that need to be incorporated to account for the diversity of causal connections in the biological sciences. Furthermore, it is argued that recognizing natural variability in mechanisms, such as attenuation, leads to some interesting line-drawing issues for contemporary philosophy of mechanisms.

Modern health care relies extensively on the use of technologies forassessing and treating patients, so it is important to be certain that health care technologies (i.e., pharmaceuticals, devices, procedures, and organizational systems) perform their professed functions in an effective and safe manner. Philosophers of technology have developed methods to assign and evaluate the functions of technological products, the major elements of which are described in the ICE theory. This paper questions whether the standard of evidence advocated by the ICE theory is adequate for ascribing and assessing technologies employed in health care. The paper proposes that the general problem with the standard of evidence embodied in the ICE theory (i.e.,testimony and evidence of mechanisms) is too permissive for assessing medical technologies, in that it does not take into account the relative benefit and harm of medical technologies in ensuring safe functional performance in patients. The paper illustrates how evidence-based medicine (EBM) has demonstrated the value of clinical research methods, including observational studies, randomized and non-randomized clinical trials, and formal techniques, such as meta-analysis, to measure therapeutic effectiveness. I argue, therefore, that evidence from clinical research studies should take precedence over the testimonial evidence and other types of non-clinical evidence, inproviding justification for health technologies.