Inventing the Randomized Double-Blind Trial: The Nuremberg Salt Test of 1835

Stolberg, Michael

doi:10.1177/014107680609901216

Cited by 17 publications

(11 citation statements)

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“…Disapproving reactions to experimentation may partly reflect a lack of familiarity. The first true randomized experiment was conducted less than two centuries ago (25), and the statistical theory underlying experiments dates only to the 1920s (26, 27). A/B tests are therefore not an intuitive, common-sense, evidence-creating mechanism, and they may simply be hard for us to think clearly about.…”

Section: Discussionmentioning

confidence: 99%

Objecting to experiments that compare two unobjectionable policies or treatments

Meyer

Heck

Holtzman

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Randomized experiments have enormous potential to improve human welfare in many domains, including healthcare, education, finance, and public policy. However, such “A/B tests” are often criticized on ethical grounds even as similar, untested interventions are implemented without objection. We find robust evidence across 16 studies of 5,873 participants from three diverse populations spanning nine domains—from healthcare to autonomous vehicle design to poverty reduction—that people frequently rate A/B tests designed to establish the comparative effectiveness of two policies or treatments as inappropriate even when universally implementing either A or B, untested, is seen as appropriate. This “A/B effect” is as strong among those with higher educational attainment and science literacy and among relevant professionals. It persists even when there is no reason to prefer A to B and even when recipients are treated unequally and randomly in all conditions (A, B, and A/B). Several remaining explanations for the effect—a belief that consent is required to impose a policy on half of a population but not on the entire population; an aversion to controlled but not to uncontrolled experiments; and a proxy form of the illusion of knowledge (according to which randomized evaluations are unnecessary because experts already do or should know “what works”)—appear to contribute to the effect, but none dominates or fully accounts for it. We conclude that rigorously evaluating policies or treatments via pragmatic randomized trials may provoke greater objection than simply implementing those same policies or treatments untested.

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Section: Discussionmentioning

confidence: 99%

Objecting to experiments that compare two unobjectionable policies or treatments

Meyer

Heck

Holtzman

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Although he never used the term placebo, Hahnemann was obviously aware of its clinical "potency." Similarly, the famous "Nuremberg Salt Test" of 1835 (Stolberg, 2006) (designed to disprove Hahnemann's homeopathic concept) used "pure snow water" as a control for the "saline treatment" that was a popular homeopathic treatment around that time, also without mentioning the term placebo. For more details/information on this and other examples, we refer the interested reader to Ted Kaptchuk's article on the history of blind assessment and placebo controls in medicine (Kaptchuk, 1998).…”

Section: Placebo Responsementioning

confidence: 99%

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

Schedlowski¹,

Enck²,

Rief³

et al. 2015

Pharmacol Rev

266

257

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“…Although placebos have been used in general medicine for almost 200 years, 1 their use in psychiatry is less well documented (panel). 3 Systematic use of placebos in drug trials and beyond is, however, restricted to the past 60 years.…”

Section: Introductionmentioning

confidence: 99%

Placebo effects in psychiatry: mediators and moderators

Weimer¹,

Colloca

Enck³

2015

The Lancet Psychiatry

187

166

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A strong placebo response in psychiatric disorders has been noted for the past 50 years and various attempts have been made to identify predictors of it, by use of meta-analyses of randomised controlled trials and laboratory studies. We reviewed 31 meta-analyses and systematic reviews of more than 500 randomised placebo-controlled trials across psychiatry (depression, schizophrenia, mania, attention-deficit hyperactivity disorder, autism, psychosis, binge-eating disorder, and addiction) for factors identified to be associated with increased placebo response. Of 20 factors discussed, only three were often linked to high placebo responses: low baseline severity of symptoms, more recent trials, and unbalanced randomisation (more patients randomly assigned to drug than placebo). Randomised controlled trials in non-drug therapy have not added further predictors, and laboratory studies with psychological, brain, and genetic approaches have not been successful in identifying predictors of placebo responses. This comprehensive Review suggests that predictors of the placebo response are still to be discovered, the response probably has more than one mediator, and that different and distinct moderators are probably what cause the placebo response within psychiatry and beyond.

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Inventing the Randomized Double-Blind Trial: The Nuremberg Salt Test of 1835

Abstract: Additional material for this article is available from the James Lind Library website [http://www.jameslindlibrary.org], where this paper was previously published.

Cited by 17 publications

References 1 publication

Objecting to experiments that compare two unobjectionable policies or treatments

Objecting to experiments that compare two unobjectionable policies or treatments

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

Placebo effects in psychiatry: mediators and moderators

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