In times of crises, public health leaders may claim that trials of public health interventions are unethical. One reason for this claim can be that equipoise—i.e. a situation of uncertainty and/or disagreement among experts about the evidence regarding an intervention—has been disturbed by a change of collective expert views. Some might claim that equipoise is disturbed if the majority of experts believe that emergency public health interventions are likely to be more beneficial than harmful. However, such beliefs are not always (...) justified: where high quality research has not been conducted, there is often considerable residual uncertainty about whether interventions offer net benefits. In this essay we argue that high-quality research, namely by means of well-designed randomized trials, is ethically obligatory before, during, and after implementing policies in public health emergencies (PHEs). We contend that this standard applies to both pharmaceutical and non-pharmaceutical interventions, and we elaborate an account of equipoise that captures key features of debates in the recent pandemic. We build our case by analyzing research strategies employed during the COVID-19 pandemic regarding drugs, vaccines, and non-pharmaceutical interventions; and by providing responses to possible objections. Finally, we propose a public health policy reform: whenever a policy implemented during a PHE is not grounded in high-quality evidence that expected benefits outweigh harms, there should be a planned approach to generate high-quality evidence, with review of emerging data at preset time points. These preset timepoints guarantee that policymakers pause to review emerging evidence and consider ceasing ineffective or even harmful policies, thereby improving transparency and accountability, as well as permitting the redirection of resources to more effective or beneficial interventions. (shrink)

There are two competing views regarding the role of mechanistic knowledge in inferences about the effectiveness of interventions. One view holds that inferences about the effectiveness of interventions should be based only on data from population-level studies (often statistical evidence from randomised trials). The other view holds that such inferences must be based in part on mechanistic evidence. The competing views are local principles of inference, the plausibility of which can be assessed by a more general normative principle of inference. (...) Bayesianism tells us to base inferences on both the ‘likelihood’ and the ‘prior’. The likelihood represents statistical evidence. One influence on the prior probability of a hypothesis like ‘d causes x’ is mechanistic knowledge of how d causes x. Thus, reasoning about such inferences by appealing to both statistical and mechanistic evidence is vindicated by our best general theory of inference. The primary contribution of this paper is to assess the merits and weaknesses of the arguments on both sides of the debate, using the Bayesian framework. This analysis lends support to those who argue that we should base our causal inferences about interventions in part on mechanistic evidence. (shrink)

Russo and Williamson put forward the following thesis: in order to establish a causal claim in medicine, one normally needs to establish both that the putative cause and putative effect are appropriately correlated and that there is some underlying mechanism that can account for this correlation. I argue that, although the Russo-Williamson thesis conflicts with the tenets of present-day evidence-based medicine, it offers a better causal epistemology than that provided by present-day EBM because it better explains two key aspects of (...) causal discovery. First, the thesis better explains the role of clinical studies in establishing causal claims. Second, it yields a better account of extrapolation. (shrink)

We raise a problem of applicability of RCTs to validate nuclear diagnostic imaging tests. In spite of the wide application of PET and other similar techniques that use radiopharmaceuticals for diagnostic purposes, RCT-based evidence on their validity is sparse. We claim that this is due to a general conceptual problem that we call Prevalence of Treatment, which arises in connection with designing RCTs for testing any diagnostic procedure in the present context of medical research, and is particularly apparent in this (...) case. We also identify three practical reasons why RCTs do not qualify as the best option for PET validation, which have to do with specific characteristics of nuclear diagnostic imaging, and of radiopharmaceuticals. The paper is meant to contribute both to the philosophical discussion on the EBM hierarchy of evidence, and on the specific debate on radiopharmaceuticals in nuclear medicine. (shrink)

The goal of most scientific research published in peer-review journals is to discover and report the truth. However, the research record includes tongue-in-cheek papers written in the conventional form and style of a research paper. Although these papers were intended to be taken ironically, bibliographic database searches show that many have been subsequently cited as valid research, some in prestigious journals. We attempt to understand why so many readers cited such ironic science seriously. We draw from the literature on error (...) propagation in research publication for ways categorize citations. We adopt the concept of irony from the fields of literary and rhetorical criticism to detect, characterize, and analyze the interpretations in the more than 60 published research papers that cite an instance of ironic science. We find a variety of interpretations: some citing authors interpret the research as valid and accept it, some contradict or reject it, and some acknowledge its ironic nature. We conclude that publishing ironic science in a research journal can lead to the same troubles posed by retracted research, and we recommend relevant changes to publication guidelines. (shrink)

An astonishing volume and diversity of evidence is available for many hypotheses in the biomedical and social sciences. Some of this evidence—usually from randomized controlled trials (RCTs)—is amalgamated by meta-analysis. Despite the ongoing debate regarding whether or not RCTs are the ‘gold-standard’ of evidence, it is usually meta-analysis which is considered the best source of evidence: meta-analysis is thought by many to be the platinum standard of evidence. However, I argue that meta-analysis falls far short of that standard. Different meta-analyses (...) of the same evidence can reach contradictory conclusions. Meta-analysis fails to provide objective grounds for intersubjective assessments of hypotheses because numerous decisions must be made when performing a meta-analysis which allow wide latitude for subjective idiosyncrasies to influence its outcome. I end by suggesting that an older tradition of evidence in medicine—the plurality of reasoning strategies appealed to by the epidemiologist Sir Bradford Hill—is a superior strategy for assessing a large volume and diversity of evidence. (shrink)

In 2003 and 2018 researchers discussed the perils of blind reliance on randomized controlled trials that have been substituted for medical experience and clinical acumen. Although these past articles do well to shed light on this issue, they neglect to discuss the topic of all-cause mortality in controlled trials. The current essay seeks to fill this void and expand the thought put into the appropriateness of all-cause mortality, especially when trials extend excessively far into the future. To do this effectively (...) the current essay leans on trial data from statin research and evidence from cancer screening—where researchers have explicitly called for all-cause mortality to be used in lieu of cancer or cardiovascular specific mortality. The issue with such an endpoint is that it obfuscates the issue at hand, namely that a specific intervention is intended to have a specific effect, not that a specific intervention is supposed to have any kind of effect. The effect(s) of medical interventions ought to be relevant to their intended mechanism of action and not simply any positive effect that can be pulled from trial data. (shrink)

Francesco Guala once wrote that ‘The problem of extrapolation is a minor scandal in the philosophy of science’. This paper agrees with the statement, but for reasons different from Guala’s. The scandal is not, or not any longer, that the problem has been ignored in the philosophy of science. The scandal is that framing the problem as one of external validity encourages poor evidential reasoning. The aim of this paper is to propose an alternative—an alternative which constitutes much better evidential (...) reasoning about target systems of interest, and which makes do without consideration of external validity. (shrink)

This article looks at the ethical quandaries, and their social and political context, which emerge as a result of international nuclear waste substitution. In particular it addresses the dilemmas inherent within the proposed return of nuclear waste owned by Japanese nuclear companies and currently stored in the United Kingdom. The UK company responsible for this waste, British Nuclear Fuels Limited (BNFL), wish to substitute this high volume intermediate-level Japanese-owned radioactive waste for a much lower volume of much more highly radioactive (...) waste. Special focus is given to ethical problems that they, and the UK government, have not wished to address as they move forward with waste substitution. The conclusion is that waste substitution can only be considered an ethical practice if a set of moderating conditions are observed by all parties. These conditions are listed and, as of yet, they are not being observed. (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)

This article looks at the ethical quandaries, and their social and political context, which emerge as a result of international nuclear waste substitution. In particular it addresses the dilemmas inherent within the proposed return of nuclear waste owned by Japanese nuclear companies and currently stored in the United Kingdom. The UK company responsible for this waste, British Nuclear Fuels Limited (BNFL), wish to substitute this high volume intermediate-level Japanese-owned radioactive waste for a much lower volume of much more highly radioactive (...) waste. Special focus is given to ethical problems that they, and the UK government, have not wished to address as they move forward with waste substitution. The conclusion is that waste substitution can only be considered an ethical practice if a set of moderating conditions are observed by all parties. These conditions are listed and, as of yet, they are not being observed. (shrink)

Since the advent of drug regulation in 1962, regulatory agencies have been in the practice of using strict standards to test the safety and efficacy of medical treatments and products. Regulatory agencies, such as the FDA, demand two full-fledged Randomized Clinical Trials demonstrating the safety and effectiveness of drugs to grant its marketing authorization. On the contrary, surgical treatments are left completely unregulated. There are several reasons explaining this difference, and all of them point to the difficulty of conducting well-designed (...) RCTs in surgery. However, we argue that none of these arguments is decisive and that, under certain conditions, surgical RCTs can be morally justified and methodologically sound. Although ethical constraints restrict the number of testable surgical procedures, and surgical trials might not be as dependable as pharmaceutical RCTs, our analysis suggests that, in certain cases, it is possible to obtain high-quality evidence about the safety and efficacy of surgical procedures. Untested surgical treatments may prove to be ineffective and harm patients. Therefore, regulation of surgical procedures seems not only morally acceptable and able to provide reliable scientific evidence, but also desirable and justified from an ethical-political standpoint. (shrink)

There is an international consensus that medical research involving humans should only be undertaken in accordance with ethical principles. Paradoxically though, there is no consensus over the kinds of activities that constitute research and should be subject to review. In the UK and elsewhere, research requiring review is distinguished from clinical audit. Unfortunately the two activities are not always easy to differentiate from one another. Moreover, as the volume of audit increases and becomes more formal in response to the demand (...) for evidence-based practice in medicine, the overlap between research and audit grows more acute. Arguably, similar ethical standards and systems for ensuring that those standards are met should be applied regardless of whether or not a project is classified as research or audit. At a time when the research ethics review system in the UK is undergoing significant reform it is important that the opportunity is not missed to address the longstanding research-audit problem. We discuss suggestions for further reform that addresses this issue. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best methods will (...) favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)