https://orcid.org/0000-0002-6511-4792
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ABSTRACT
Establishing the effectiveness of medical treatments is one of the most important aspects of medical practice. Bradford Hill's viewpoints play an important role in inferring causality in medicine, and EBM+ seeks to improve evidence-based medicine, which is influential in establishing treatment effectiveness. At EBM+'s foundations lies the Russo–Williamson thesis (RWT), which can be seen as providing a reduction of Hill's viewpoints into those involving difference-making and mechanistic evidence, both of which are claimed by the RWT's proponents to be typically required for establishing causal claims in medicine. Yet little has been written on whether and how the RWT, EBM+, and Hill's viewpoints establish treatment effectiveness. This could be because of uncertainty over what treatment effectiveness is. I provide an account of treatment effectiveness, analysing the role of the RWT, EBM+, and Hill's viewpoints in this regard. I argue that Hill's viewpoints and EBM+ can be useful in helping to evaluate evidence, but cannot directly establish or confirm treatment effectiveness. This is partly because effectiveness, I claim, is subject to inductive risk and therefore determined by non-epistemic values, neither of which Hill's viewpoints nor EBM+ offer guidance on. I conclude by reinterpreting Hill's viewpoints in light of establishing treatment effectiveness.
Acknowledgements
Thanks to two anonymous reviewers for International Studies in the Philosophy of Science for helpful comments, and especially one of these reviewers for encouraging me to expand my account of treatment effectiveness, and for many other helpful comments. I am grateful to Federica Russo for reviewing an early draft and to Bennett Holman for reviewing one part of the final draft.
Disclosure Statement
No potential conflict of interest was reported by the author(s).
Notes
1 According to Williamson (Citation2019, 36) ‘“appropriately correlated” just means probabilistically dependent conditional on potential confounders, where the probability distribution in question is relative to a specified population or reference class of individuals.’
2 Clinical trials include, inter alia, RCTs; observational trials whereby the investigator observes outcomes without providing an intervention, such as case-control, cross-sectional, and cohort studies; case series; and N-of-1 trials.
3 Though as Leuridan and Weber (Citation2011) note, examples attempting to show the RWT to be undermined could also be interpreted as calls for the associated claim of effectiveness to be amended.
4 I thank an anonymous reviewer for this journal for the lattermost point.
5 In the interest of space, I only discuss my own, in the next section.
6 One might nonetheless try to rely on the efficacy-effectiveness distinction to argue that RCTs (or, specifically, explanatory RCTs as opposed to pragmatic RCTs) are used to assess the efficacy of treatments whereas observational studies (and pragmatic RCTs) assess effectiveness. This distinction, however, is problematic and typically either just indicates the method by which a treatment is studied, or the population/setting in question (i.e. a study/research setting, or target population/clinical practice), but does not indicate anything intrinsic about a treatment's effectiveness (Tresker Citationforthcoming). In the next section I offer an account of effectiveness that, in the case of an individual patient in clinical practice, looks at how a treatment is likely to affect that patient. In this regard, both so-called efficacy and effectiveness trials can produce evidence of effectiveness, since in both cases inferences will need to be made regarding how the treatment will affect a given patient in clinical practice.
7 For reasons of space I restrict my discussion of treatment effectiveness claims to the individual case and leave a discussion of treatment effectiveness claims for populations (such as might be made by researchers, regulatory authorities, health insurers, etc.) to potential future work.
8 Nonetheless, N-of-1 trials, although primarily just suitable for chronic, symptomatic conditions with easily measurable clinical outcomes, could provide useful information about treatment effectiveness, though typically only for the patient subject to the trial (Lillie et al. Citation2011; Duan, Kravitz, and Schmid Citation2013).
9 While a patient's treatment decision can be considered in the context of a benefit–cost analysis, there may be good reasons for an effectiveness claim to be seen as an input to this analysis and not as equivalent to the outcome. In work in progress, I articulate how better understanding and facilitating treatment decision-making in the context of a clinical encounter, particularly from a shared decision-making standpoint, can help to better understand the contours of how treatment effectiveness claims can be integrated into decision theory.
10 This is not to say that plausible mechanisms of the effects of acupuncture on nausea do not exist; see Chen et al. (Citation2014), for example, for some possibilities, although some acupuncture researchers claim that the mechanisms remain undiscovered (Shi et al. Citation2019).
11 Although Gillies's account of acupuncture is problematic this should not be seen as impugning EBM+ as a whole, since alternative EBM+-inspired analyses might reach different conclusions. Moreover, Gillies should not be faulted, because rather than provide a rigorous substantive analysis of the effectiveness of acupuncture his chief aim appears to have been to illustrate the importance of mechanisms for establishing causal claims in medicine, for which I think he is successful.
12 ‘NegC’ reasoning in his typology whereby meta-mechanistic reasoning is used to argue that there is no plausible mechanistic chain between the putative cause and effect.
13 Illustrated by clinical practice guidelines (CPGs) when some experts hold diametrically opposed viewpoints. For example, CPGs promulgated by the American Academy of Orthopaedic Surgeons (Citation2013) strongly recommended against viscosupplementation for the treatment of osteoarthritis (OA) of the knee, despite statistically significant results versus placebo, based on what they saw as clinical insignificance for some patients. This was met with strong resistance by physicians and industry members (Peer Review & Public Comments and AAOS Responses Citation2012). As Lubowitz, Provencher, and Poehling (Citation2014, 4, italics in original) opined, ‘In our opinion, it is not in the interests of all patients to recommend against a treatment that is of significant benefit for some patients, especially when that treatment is for a disease (knee OA) that is not preventable, and for which there is no cure.’ This example also illustrates how non-epistemic values can influence effectiveness claims, and the importance of not conflating effectiveness determinations with treatment recommendations or decisions.
14 EBM+ proponents might argue that both sets of evidence should be evaluated and a conclusion drawn from that. However, it is unclear how such conclusions can be drawn using an EBM+ framework. Parkinnen and colleagues (Citation2018, 74), for example, in offering an example of an intervention to which an EBM+ analysis could apply, subsequently state, ‘We did not undertake a systematic review of the evidence on how probiotics might work.’ This implies an actual substantive investigation is needed, possibly rendering the philosophical work otiose.
15 In this regard, use of the Template for Intervention Description and Replication (TIDieR-Placebo) checklist (Howick et al. Citation2020) could be used alongside EBM+'s checklists, given that it allows key features of both active interventions and placebo or sham controls to be concisely summarised by researchers, and also whether blinding was successful. Since this can easily be integrated with EBM, this seems like something that could also be integrated with EBM+.
16 As Howick (Citation2011b) indicates, EBM's view of evidence is fundamentally based on hierarchies of methods of generating evidence. If this is true then it is not clear how EBM+ merits the EBM appellation given its apparent abandonment of evidence hierarchies by viewing mechanistic evidence on the same footing as difference-making evidence.
17 Some of these may very well be concerns shared by members of the EBM+ community, so my arguments should be construed less as criticism and more as spotlighting areas where EBM+ can be built upon.
18 Despite their popularity, Hill's viewpoints—even with respect to disease causation—have received their fair share of criticism (e.g. Rothman and Greenland [Citation2005]). Hill's viewpoints are not well-defined conditions and it is not clear what is required for any given viewpoint to be satisfied, much less how they can be weighted and integrated to establish causation (Phillips and Goodman Citation2006). According to Ward (Citation2009), Hill's viewpoints do not justify inferring that a statistical association is causal.
19 For example, Dammann (Citation2018, 3) raises the point that since Hill didn't require all of the viewpoints be fulfilled for a causal claim to be supported and no single one (with the exception of temporality) to be necessary, claiming as Russo and Williamson do that Hill's guidelines express principles of the RWT elides over the fact that the RWT requires at least some of the viewpoints (namely, those expressing mechanistic and difference-making evidence) to be necessary.