Abstract
Debates about the ethics and effects of placebos and whether ‘placebos’ in clinical trials of complex treatments such as acupuncture are adequate (and hence whether acupuncture is ‘truly’ effective or a ‘mere placebo’) rage. Yet there is currently no widely accepted definition of the ‘placebo’. A definition of the placebo is likely to inform these controversies. Grünbaum’s (1981, 1986) characterization of placebos and placebo effects has been touted by some authors as the best attempt thus far, but has not won widespread acceptance largely because Grünbaum failed to specify what he means by a therapeutic theory and because he does not stipulate a special role for expectation effects. Grünbaum claims that placebos are treatments whose ‘characteristic features’ do not have therapeutic effects on the target disorder. I show that with four modifications, Grünbaum’s definition provides a defensible account of placebos for the purpose of constructing placebo controls within clinical trials. The modifications I introduce are: adding a special role for expectations, insisting that placebo controls control for all and only the effects of the incidental treatment features, relativizing the definition of placebos to patients, and introducing harmful interventions and nocebos to the definitional scheme. I also provide guidance for classifying treatment features as characteristic or incidental.
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Notes
Note however that if the effect of the vitamin C were very large—suppose for example that everyone’s cold cleared up immediately, then we could be quite certain that vitamin C caused the recovery. This judgment would be justified by a hypothetical control group: background knowledge informs us that colds take several days to go away on their own and without treatment.
Medical scientists often talk of the non-blind studies ‘exaggerating’ the benefits of treatment, but since if the treatment is approved it will be carried out by practitioners in a non-blind way the non-blind results may well in fact give a more accurate measure of the ‘real result’ in ‘the wild’.
Grünbaum uses F to designate characteristic factors and C to designate incidental factors. I use the more natural ‘C’ and ‘I’.
Henceforth unless otherwise specified when referring to the term ‘placebo’ I mean ‘generic placebo’.
It is important to note the difference between expectancy and conditioning. Expectancy and conditioning are activated by overlapping but different stimuli, are known to operate via different mechanisms and have different effects (Stewart-Williams and Podd 2004). But by definition in the case of the unconscious patients we are controlling for unconscious expectations. Unconscious expectancy is generally regarded as distinct from (conscious) expectancy and is referred to by a different name: conditioning. Hence while the conditioned response of the unconscious patient and the additional practitioner enthusiasm may be incidental (placebo) factors, they are not the same thing as (conscious) expectancy.
I ignore here the issue of whether the device is indistinguishable from ‘real’ acupuncture and hence whether it has been ‘validated’ in the sense proponents claim; evidence suggests it is not (see Howick 2011).
These are not the only treatments for which it is difficult to construct adequate placebo controls. How, for example, would we design a ‘placebo’ control for exercise? That is, how could we make people expect to be doing exercise (and experience the effects of all other incidental features—whatever those turn out to be) without actually doing exercise (Howick 2011)? One might suggest we could hypnotize people to believe they are doing exercise. However hypnosis has its own effects (Lee et al. 2010). Thornier still is the example of electroconvulsive therapy (ECT), which is the electrical induction of seizures in patients. ECT is used to treat patients suffering from major depressive disorder who have not responded to other forms of therapy. It is difficult to imagine an adequate ‘placebo’ control for ECT. Worse, even if we could design an adequate placebo control, as Blease points out, ECT has so many deleterious side-effects (confusion, memory loss, fatigue, headaches, and general cognitive impairment (Blease 2013a, b)) that it could arguably be unethical.
Placebo controlled trials may have some advantages compared with head to head trials that compare one intervention with another, and vice-versa. Discussion of the debate of the relative methodological advantages of placebo compared with other standard treatment controls is beyond the scope of the current paper. Suffice it to say that each design has relative advantages and disadvantages, and that there is no widespread consensus about the absolute superiority of one method is superior to another. See Howick (2009a, b) for further discussion.
Introducing ‘active’ placebos presents two new problems. First, it is ethically questionable to introduce harm to the control group in a controlled trial. Second (and this has usually gone unnoticed) when measuring incidence of side effects in clinical trials, comparisons between outcomes in treatment and control groups are made. But if the side effects were introduced to the control group, we would not expect any differences. This can lead to mistaken claims about the side effect profile of a new intervention.
It is, of course, problematic to determine in advance which patients will benefit, and which might be harmed by a treatment (although there are examples where genetic testing helps in this respect). This interesting epistemological problem, however, is orthogonal to my current ontological investigation into the nature of placebo controls.
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Acknowledgments
Special thanks to my Ph.D. supervisor John Worrall, with whom this paper was developed. Most of the ideas and much of the writing of the first two sections of the paper is John’s. Thanks also to Nancy Cartwright and Michael Hardimon who both commented on earlier drafts of this paper, to Sir Iain Chalmers for insisting that I use real examples wherever possible, to the University of California at San Diego Graduate Conference attendees (organized by Michael Hardimon), to attendees of the “Evidence in Science and Epistemology” conference in Helsinki (especially Maria Lasonen-Aarnio, Petri Ylikoski, and Markus Lammenranta), to Have Carel and Alexander Bird for hosting me to give a talk about this paper at the University of Bristol and for providing useful comments. Andrew Turner, Frank Miller, and Wiebe Van Der Hoek gave useful feedback on earlier versions of the manuscript. Students taking part in the Oxford Philosophy of Medicine Seminar Series at All Souls, Oxford, including Matthew Clark, Meghana Mishra provided useful insights.
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This work was partly supported by the National Institute for Health Research School for Primary Care Research (NIHR SPCR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health.
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Howick, J. The relativity of ‘placebos’: defending a modified version of Grünbaum’s definition. Synthese 194, 1363–1396 (2017). https://doi.org/10.1007/s11229-015-1001-0
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DOI: https://doi.org/10.1007/s11229-015-1001-0