Novel study designs to investigate the placebo response

Paul Enck,Stephan Zipfel,Sibylle Klosterhalfen

doi:10.1186/1471-2288-11-90

Paul Enck, Stephan Zipfel + Show 1 more

Open Access

https://doi.org/10.1186/1471-2288-11-90

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Abstract

BackgroundInvestigating the size and mechanisms of the placebo response in clinical trials have relied on experimental procedures that simulate the double-blind randomized placebo-controlled design. However, as the conventional design is thought to elucidate drug rather than placebo actions, different methodological procedures are needed for the placebo response.MethodsWe reviewed the respective literature for trials designs that may be used to elucidate the size of the placebo response and the mechanisms associated with it.ResultsIn general, this can be done by either manipulation the information provided to the subjects, or by manipulation the timing of the drug applied. Two examples of each strategy are discussed: the "balanced placebo design" (BDP) and the "balanced cross-over design" (BCD) and their variants are based on false information, while the "hidden treatment" (HT) and the ""delayed response test" (DRT) are based on manipulating the time of drug action. Since most such approaches include deception or incomplete information of the subjects they are suitable for patient only with authorized deception.ConclusionBoth manipulating the information provided to subjects (BDP, DCD) or manipulating the timing of drug application (HT, DRT) allows overcoming some of the restrictions of conventional drug trials in the assessment of the placebo response, but they are feasible mostly in healthy subjects for ethical reasons.

Highlights

Investigating the size and mechanisms of the placebo response in clinical trials have relied on experimental procedures that simulate the double-blind randomized placebo-controlled design
The “delayed response” test A very unique approach based on such an assumption that has - to our knowledge - never been explored in any placebo testing is the following: Assume that a drug can elicit its action at a predefined time point hours after ingestion, either via a coating technology [52] or a radio-transmitted mechanical capsule technology [53] for controlled release of the compound; such technology has been used in many clinical conditions such as diabetes, Alzheimer dementia and other conditions
Investigating the size and mechanisms of the placebo response in different medical conditions has relied on experimental procedures that simulate the double-blind randomized placebo-controlled design of clinical trials

Summary

Results

This can be done by either manipulation the information provided to the subjects, or by manipulation the timing of the drug applied. Two examples of each strategy are discussed: the “balanced placebo design” (BDP) and the “balanced cross-over design” (BCD) and their variants are based on false information, while the “hidden treatment” (HT) and the “"delayed response test” (DRT) are based on manipulating the time of drug action. Since most such approaches include deception or incomplete information of the subjects they are suitable for patient only with authorized deception

Conclusion

Conclusions

Hill AB

14. Ondo WG

33. Kirsch I

51. Machado L