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Treatment effectiveness, generalizability, and the explanatory/pragmatic-trial distinction

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Abstract

The explanatory/pragmatic-trial distinction enjoys a burgeoning philosophical and medical literature and a significant contingent of support among philosophers and healthcare stakeholders as an important way to assess the design and results of randomized controlled trials. A major motivation has been the need to provide relevant, generalizable data to drive healthcare decisions. While talk of pragmatic and explanatory trials could be seen as convenient shorthand, the distinction can also be seen as harboring deeper issues related to inferential strategies used to evaluate causal claims regarding medical treatments. A comprehensive, critical analysis of the distinction and underlying epistemological framework upon which the distinction is based, particularly with respect to treatment effectiveness, has yet to be forthcoming. I provide this, analyzing the distinction’s relationship to generalizability and cognate distinctions between ideal conditions and real-world practice, internal and external validity, and efficacy and effectiveness. I also analyze recent philosophical work that relies on the explanatory/pragmatic-trial distinction and that advocates for more pragmatic trials. I conclude that as an organizing principle for trial-design decisions and trial evaluation, the explanatory/pragmatic-trial distinction is conceptually problematic and not as useful as its proponents seem to think. Since some pragmatic-trial features can be inimical to establishing treatment effectiveness, pragmatic-trial features should not be conflated with pragmatic trials’ avowed goals. If the distinction is to be useful, it and some associated concepts, including generalizability, should be reformulated, lest they continue to underlie a medical epistemology that could contribute to methodologically flawed and potentially unethical advice for the design and interpretation of trials.

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Notes

  1. I henceforth simply refer to pragmatic or explanatory RCTs as pragmatic or explanatory trials, based on the assumption that all explanatory and pragmatic trials are RCTs. This is not a universally accepted assumption, though (e.g. Porzsolt et al., 2015). To insist on randomization as excluding whether a trial is pragmatic, however, collapses the distinction between RCTs and non-randomized observational studies in a way many authors (e.g. Thorpe et al., 2010) might be uncomfortable with and elevates randomization to a level that does not do justice to the many other trial features that determine how closely “real-world” conditions are approximated. The explanatory/pragmatic-trial distinction is best thought of as a multidimensional continuum (whereby trials can be somewhat explanatory and somewhat pragmatic and as having some explanatory-trial and pragmatic-trial features), although it could be viewed as a dichotomy when, for example, contrasting a very explanatory trial with a very pragmatic trial. To be clear, my purpose in this article is not to argue against it being a simplistic distinction, and in fact many authors (e.g. Borgerson 2013; Schwartz and Lellouch 1967; Thorpe et al., 2009) explicitly see the distinction as not a simplistic one.

  2. The status of blinding in pragmatic trials is not universally agreed upon: Williams et al. (2015) think pragmatic trials should always involve blinding when possible, Dal-Ré et al. (2018) think pragmatic trials should avoid blinding of treatment assignment, Thorpe et al. (2009) think blinding is not inconsistent with a pragmatic trial, while other authors (Maningat and Breslow 2011; Ware and Hamel 2011) think blinding is often omitted in pragmatic trials.

  3. There are few philosophical accounts of treatment effectiveness, Ashcroft’s (2002) and Stegenga’s (2015) being notable exceptions. Because I offer in other work more developed accounts of medical treatment (under review) and of treatment effectiveness (Tresker, 2022), I only present a sketch here.

  4. A treatment’s effectiveness supervenes on the set of its true treatment effectiveness claims. In practice it is rarely if ever known for certain what a treatment’s full set of true treatment effectiveness claims is. Knowledge of a treatment’s effectiveness is in most cases partial and subject to some level of uncertainty, given the fallibility of medical knowledge. Actual treatment effectiveness claims are at best well-confirmed, empirically well-supported, practically reliable, etc. I thank Bert Leuridan for these points in this footnote, and for suggesting that I pay close attention to not conflate the ontic with the epistemic.

  5. How to amalgamate evidence informing a treatment effectiveness claim, and how to evaluate the evidence’s warrant, are of course crucial questions but are beyond the scope of this article.

  6. Hey and Weijer (2013, p. 3), for example, note that no single well-designed trial can provide sufficient evidence of effectiveness. This is not to say that not viewing effectiveness as comprising a prediction but instead as an extrapolatable trial result entails the view that single studies or types of studies establish effectiveness, but it does seem to make it more likely, especially when stakeholders use RCTs as dispute-resolution mechanisms (Deaton & Cartwright, 2018).

  7. In this respect even something as simple as, “This treatment will likely make me feel better” may provide a relevant notion of effectiveness for a patient in clinical practice. Such a prediction does not match any outcome measure from a study (RCT or otherwise), yet it may be all a patient is able to fathom, and could suffice as the key part of an argument for a useful treatment effectiveness claim.

  8. Fuller (2013, p. 644) offers a better description of generalizability as asking what useful inferences can be made from RCT results.

  9. Many thanks to Bert Leuridan for suggesting I fully expand the typology beyond the abbreviated version I originally had.

  10. I thank Jonathan Fuller for suggesting the third type.

  11. Alternatively, a different term than “generalizability” could be used, or a qualification added (e.g. “generalizability for treatment effectiveness claims”). I retain “generalizability” for prudential reasons, and unless otherwise indicated use it henceforth throughout this article according to the reformulated meaning I propose.

  12. Reiss’s (2015) pragmatist theory of evidence (which does not pertain to pragmatic trials) also looks at the question(s) to be answered by a trial and what evidence could warrant a successful outcome. Similarly, Cartwright (2010, p. 69) thinks, “the best way to evaluate effectiveness claims is by the construction of a causal model, where information about the behaviour of C in an RCT is only one small part of the information needed to construct the model.”

  13. Although this was not the case when Schwartz and Lellouch wrote, the recent growth of interest in “learning healthcare systems” (of which pragmatic trials benefit and benefit from; Tuzzio and Larson 2019) is partly based on the idea that all clinician–patient encounters can in principle elicit information that bears on causal hypotheses. This can contribute to the implementation of trial results into clinical practice and aid both understanding and decision. I thank an anonymous reviewer for this journal for this point.

  14. And guidance sought from whether criteria (such as those articulated by Hey and Weijer 2016) are satisfied for when placebo controls are ethically allowed.

  15. Notwithstanding this, causation in clinical care and in studies of its tools is complex and in many cases opaque, likely affected by factors not included or studied in a trial, such as molecular and genetic components. I thank an anonymous reviewer for this journal for this point.

  16. Nonetheless, comparative effectiveness trials may indeed contribute to better inferences to treatment effectiveness claims than placebo-controlled trials, in addition to often being ethically mandated.

  17. This should not be misinterpreted as the claim that placebo-controlled trials are superior to active-controlled trials.

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Acknowledgements

I am deeply indebted to three anonymous reviewers for this journal whose expertise, close reading of the manuscript, and highly insightful comments helped me avoid many mistakes, clarify my claims, and overall present a stronger argument. This work would not have been the same without their input. Many thanks to Bert Leuridan, Jonathan Fuller, Andreas De Block, and María Jiménez-Buedo for helpful reviews of the final or almost-final versions.

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The author was supported by the Fonds Voor Wetenschappelijk Onderzoek – Vlaanderen (FWO; Research Foundation – Flanders; 1130819N) during the writing of this article.

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  1. Centre for Philosophical Psychology, Department of Philosophy, University of Antwerp, Stadscampus – Rodestraat 14, 2000, Antwerp, Belgium

    Steven Tresker

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Correspondence to Steven Tresker.

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Tresker, S. Treatment effectiveness, generalizability, and the explanatory/pragmatic-trial distinction. Synthese 200, 316 (2022). https://doi.org/10.1007/s11229-022-03517-0

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