Evidence hierarchies are widely used to assess evidence in systematic reviews of medical studies. I give several arguments against the use of evidence hierarchies. The problems with evidence hierarchies are numerous, and include methodological shortcomings, philosophical problems, and formal constraints. I argue that medical science should not employ evidence hierarchies, including even the latest and most-sophisticated of such hierarchies.

Proponents of evidence-based medicine and some philosophers of science seem to agree that knowledge of mechanisms can help solve the problem of applying results of controlled studies to target populations (‘the problem of extrapolation’). We describe the problem of extrapolation, characterize mechanisms, and outline how mechanistic knowledge might be used to solve the problem. Our main thesis is that there are four often overlooked problems with using mechanistic knowledge to solve the problem of extrapolation. First, our understanding of mechanisms is (...) often (and arguably, likely to remain) incomplete. Secondly, knowledge of mechanisms is not always applicable outside the tightly controlled laboratory conditions in which it is gained. Thirdly, mechanisms can behave paradoxically. Fourthly, as Daniel Steel points out, using mechanistic knowledge faces the problem of the ‘extrapolator’s circle’. At the same time, when the problems with mechanistic knowledge have been addressed, such knowledge can and should be used to mitigate (nothing can entirely solve) the problem of extrapolation. (shrink)

Psychedelics are currently being studied intensively for the treatment of various psychiatric disorders. Ayahuasca, a plant-based extract originating from the Amazonian area, is traditionally consumed in ritualistic group events. The related indigenous traditions date back hundreds of years and have amassed vast amounts of knowledge on the therapeutic use of psychedelic and non-psychedelic plant-based substances. -/- These traditions require a prospective ceremony facilitator to undergo years of intensive training to acquire knowledge, mental power or self-confidence, stability, sensitivity, intuitive treatment outcome (...) prediction skills, musical skills, and sufficient physical strength. These qualities of a facilitator, in the presence of integrity and love, largely determine treatment outcomes. -/- In Europe, predominantly in the first decade of the 2000s and in the early 2010s, some individuals began building connections with diverse indigenous groups and syncretic churches of the Amazonia in an attempt to find cures for their treatment-resistant psychiatric conditions. Small circles of other patients in need of similar treatment formed around them. This led to the formation of decentralized, diverse local ceremony cultures that either followed the principles of the traditional lineages of their origin or synthesized various influences. -/- These unofficial ceremony contexts appeared to complement official healthcare systems, offering efficient methods unavailable in the medical context and correcting the consequences of medical malpractice and neglect. These ceremony contexts appeared highly communal, were largely based on volunteering, and contained mechanisms for self-correcting possible emerging issues. They seemed to function as systems for collecting, preserving, storing, and distributing knowledge of psychedelic therapy methods; in other words, systems for knowledge base building and innovation. -/- doi: 10.13140/RG.2.2.27385.85602. (shrink)

Evidence-Based Medicine has little consideration for mechanisms and philosophers of science and medicine have recently made pleas to increase the place of mechanisms in the medical evidence hierarchy. However, in this debate the notions of mechanisms seem to be limited to 'mechanistic processes' and 'complex-systems mechanisms,' understood as 'componential causal systems'. I believe that this will not do full justice to how mechanisms are used in biological, psychological and social sciences and, consequently, in a more biopsychosocial approach to medicine. Here, (...) I propose, following (Kuorikoski, 2009), to pay more attention to 'abstract forms of interaction' mechanisms. The present work scrutinized review articles on depression and medically unexplained pain, which are considered to be of multifactorial pathogenesis, for their use of mechanisms. In review articles on these disorders there seemed to be a range of uses between more 'abstract forms of interaction' and 'componential causal system' mechanisms. I therefore propose to expand the notions of mechanisms considered in medicine to include that of more 'abstract forms of interaction' to better explain and manage biopsychosocial disorders. (shrink)

Evidence-based medicine (EBM) has long deemphasized mechanistic reasoning and pathophysiological rationale in assessing the effectiveness of interventions. The EBM+ movement has challenged this stance, arguing that evidence of mechanisms and comparative studies should both be seen as necessary and complementary. Advocates of EBM+ provide a combination of theoretical arguments and examples of mechanistic reasoning in medical research. However, EBM+ proponents have not provided recent examples of how downplaying mechanistic reasoning resulted in worse medical results than would have occurred otherwise. Such (...) examples are necessary to make the case that EBM+ responds to a problem in clinical practice that urgently demands a solution. In light of this, we examine the failed rollout of efavirenz as a first-line HIV treatment in Zimbabwe as evidence of the importance of mechanistic reasoning in improving clinical practice and public health policy decisions. We suggest that this case is analogous to examples commonly given to support EBM. (shrink)

This article describes a case of a teenager with early complex trauma due to chronic domestic violence. Cannabis use triggered auditory hallucinations, after which the teenager was diagnosed with an acute schizophrenia-like psychotic disorder. Antipsychotic medication did not fully resolve symptoms. Eventually the teenager chose to self-medicate with LSD in order to resolve a suicidal condition. The teenager carried out six unsupervised LSD sessions, followed by an extended period of almost daily use of inhaled low-dose DMT. Psychotic symptoms were mostly (...) resolved after approximately one year. Subsequent cannabis use caused a transient relapse. -/- While his psychosis may have been due to cannabis use in the presence of a genetic predisposition, LSD and DMT did not promote psychotic symptoms in this case, and resolved the suicidal condition in one session. Additional high-dose LSD sessions and low-dose DMT sessions appeared to resolve the symptoms related to the early complex trauma. Alternatively, if psychosis is understood as a massive defense system resulting from early complex trauma, and if his psychotic symptoms were partially due to such trauma, psychedelics appeared to transcend this defense system, providing access to traumatic memories in order to allow for an integrative treatment effect. -/- Information was acquired from medical record excerpts provided by the patient, a semi-structured retrospective video interview, and follow-up interviews a year later. The present case suggests a need for further studies on the relationship between psychedelics and psychotic disorders, the feasibility of supervised vs unsupervised settings for various situations, and alternative therapeutic models for utilizing the hyperaware-hypersensitive state induced by psychedelics. With regard to self-treatment, a harm reduction approach should be adopted. Low-risk psycholytic self-treatment protocols could be developed for future use in public health care systems. (shrink)

This dissertation explores the influence of time constraints on different research practices. The first two parts present case studies, which serve as a basis for discussing the epistemological and ethical implications of temporal limitations in scientific research. Part I is a case study on gravitational wave research, conducted by the LIGO Scientific Collaboration. This exemplifies fundamental research – without immediate societal applications, open-ended in terms of timeline and in terms of research goals. It is based, in part, on qualitative interviews (...) conducted with gravitational wave physicists. I show that considerations about time and speed play a role in every stage of research: goal setting, method design, and the evaluation and communication of results. Part II provides a case study on translational medicine, an approach explicitly dedicated to accelerating research in order to develop and implement new therapies. This epitomizes applied research with high social stakes, motivated by non-epistemic goals. Here, epistemic trade-offs between speed and reliability intersect with ethical trade-offs between different types of harms. In Part III, the insights from both of these case studies are used as the basis for a more general discussion concerning the pragmatic aspects of epistemic practices, especially in relation to current debates centered on the role of values in science. A particular focus is on the value of speed and the ability to generate reliable results, either via choice of methods, or via decisions about which goals to set, as well as decisions about when to stop further testing. The primary thesis of the dissertation is that pragmatic considerations stemming from limitations of resources are a necessary feature of the pursuit of epistemic aims, and that the epistemic is thus inherently pragmatic. (shrink)

The US Food and Drug Administration (FDA) is fraught with controversies over the role of values and politics in regulatory science, especially with drugs in the realm of reproductive health. Philosophers and science studies scholars have investigated the ways in which social context shapes medical knowledge through value judgments, and feminist scholars and activists have criticized sexism and injustice in reproductive medicine. Nonetheless, there has been no systematic study of values and gender norms in FDA drug regulation. I focus on (...) three questions about values in regulatory science. First, how have societal values and gender norms shaped the way that the FDA regulates drugs in the realm of reproductive health, specifically with drug labels? Second, what are the ethical, epistemic, and social consequences of these influences on regulation for women and other marginalized groups? Third, which societal values and gender norms ought to influence drug regulation about reproductive health, and how ought this happen? Integrating philosophical analysis with historical archival research and in-depth interviews, I conduct three case studies of drug labeling about reproductive health: (1) the “drug fact” about the mechanism of the morning-after pill; (2) the package inserts for patients about the health risks of oral contraceptives; and (3) the special physician labels made for prescribing drugs to pregnant women. I identify three challenges for the FDA and suggest ways to reduce the influence of sexist values and facilitate feminist alternatives. First, across these cases, I have found that there are many ways in which other concerns in reproductive medicine (such as zygotic life, fetal health, and population control) have devalued women’s health. Second, both knowledge and ignorance xvi about their reproductive health have contributed to women’s oppression, especially poor women and women of color. Finally, by avoiding the epistemic dimensions of ethics, powerful, mostly male parties in medicine (such as doctors, pharmaceutical companies, and religious institutions) have misused “informed consent,” “religious freedom,” and “paternalism” for unethical purposes. For improvement, I suggest extracting sexist values and gender norms from regulatory science that cause epistemic injustices, and I point to success stories for reforming sexism with feminism at the FDA. (shrink)

This paper assesses the epistemic challenges of giving nutrition advice to elite athletes in light of recent philosophical discussion concerning evidence-based practice. Our trust in experts largely depends on the assumption that their advice is based on reliable evidence. In many fields, the evaluation of the reliability of evidence is made on the basis of standards that originate from evidence-based medicine. I show that at the Olympic or professional level, implementing nutritional plans in real-world competitions requires contextualization of knowledge in (...) a way that contravenes the tenets of evidence-based thinking. Nutrition experts need to be able to combine and apply evidence from multiple sources, including the previous successes and failures of particular athletes. I argue that in this sense, the practice of elite sport nutrition embodies casuistic reasoning. (shrink)

Philosophers of science and medicine now aspire to provide useful, socially relevant accounts of mechanism. Existing accounts have forged the path by attending to mechanisms in historical context, scientific practice, the special sciences, and policy. Yet, their primary focus has been on more proximate issues related to therapeutic effectiveness. To take the next step toward social relevance, we must investigate the challenges facing researchers, clinicians, and policy makers involving values and social context. Accordingly, we learn valuable lessons about the connections (...) between mechanistic processes and more fundamental reasons for medical interventions, particularly moral, ethical, religious, and political concerns about health, agency, and power. This paper uses debates over the controversial morning-after pill to gain insight into the deeper reasons for the production and use of mechanistic knowledge throughout biomedical research, clinical practice, and governmental regulation. To practice socially relevant philosophy of science, I argue that we need to account for mechanistic knowledge beyond immediate effectiveness, such as how it can also provide moral guidance, aid ethical categorization in the clinic, and function as a political instrument. Such insights have implications for medical epistemology, including the value-laden dimensions of mechanistic reasoning and the “epistemic friction” of values. Furthermore, there are broader impacts for teaching research ethics and understanding the role of science advisors as political advocates. (shrink)

This highly multidisciplinary collection discusses an increasingly important topic among scholars in science and technology studies: objectivity in science. It features eleven essays on scientific objectivity from a variety of perspectives, including philosophy of science, history of science, and feminist philosophy. Topics addressed in the book include the nature and value of scientific objectivity, the history of objectivity, and objectivity in scientific journals and communities. Taken individually, the essays supply new methodological tools for theorizing what is valuable in the pursuit (...) of objective knowledge and for investigating its history. The essays offer many starting points, while suggesting new avenues of research. Taken collectively, the essays exemplify the very virtues of objectivity that they theorize—in reading them together, the reader can sense various anxieties about the dangerously subjective in our age and locate commonalities of concern as well as differences of approach. As a result, the volume offers an expansive vision of a research community seeking a communal understanding of its own methods and its own epistemic anxieties, struggling to enunciate the key problems of knowledge of our time and offer insight into how to overcome them. -/- (Contributors: Alex Csiszar, Scott Edgar, Peter Galison, Ian Hacking, Sandra Harding, Moira Howes, Paolo Savoia, Judy Segal, Joan Steigerwald, and Alison Wylie). (shrink)

This chapter addresses the problem of ranking available drugs in guideline development to support clinicians in their work. Based on a pragmatic approach to the notion of evidence and a hierarchical view on different kinds of evidence this chapter introduces a decision aid, HiDAD, which draws on the multi criteria decision making literature. This decision aid implements the wide-spread intuition that there are different kinds of evidence with varying degrees of importance by relying on a strict ordinal ordering of kinds (...) of evidence. In order to construct a ranking every pair of drugs is first compared separately on all kinds of evidence. Next, these quantitative comparisons are then aggregated into an overall comparison between drugs based on all the available evidence in a way which avoids that evidence of less importance is trumped by evidence of the higher levels. Finally, these overall comparisons are used to determine the final ranking of drugs which then informs the process of guideline writing. Properties, modifications and applicability of the decision aid HiDAD are discussed and assessed. (shrink)

In this paper, we show that reproducibility is a severe problem that concerns simulation models. The reproducibility problem challenges the concept of numerical solution and hence the conception of what a simulation actually does. We provide an expanded picture of simulation that makes visible those steps of simulation modeling that are numerically relevant, but often escape notice in accounts of simulation. Examining these steps and analyzing a number of pertinent examples, we argue that numerical solutions are importantly different from usual (...) mathematical solutions. They are do not merely approximate the latter, but introduce new problems, including issues of artificiality, stability, and well-posedness. Consequently, simulation modelling can attain reproducibility only to a certain degree because it is working with numerical solutions. (shrink)