Original articles
Do medical devices have enhanced placebo effects?

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Abstract

Although the placebo in a clinical trial is often considered simply a baseline against which to evaluate the efficacy of a clinical intervention, there is evidence that the magnitude of placebo effect may be a critical factor in determining the results of a trial. This article examines the question of whether devices have enhanced placebo effects and, if so, what the implications may be. While the evidence of an enhanced placebo effect remains rudimentary, it is provocative and therefore worthy of further study. Suggestions are made, therefore, for how such an effect can be investigated without violating the principles of informed consent.

Introduction

In modern medicine, the placebo plays an indispensable but largely supportive role as a baseline from which to compare the efficacy of a drug or other therapy. Yet beyond providing a “no treatment” group, the placebo response itself may be important because its magnitude may influence the interpretation of a randomized controlled trial (RCT). For example, when an analysis was made of all the RCTs that examined the effectiveness of H2 blockers, it was found that drug effectiveness was demonstrated only in those studies whose placebo responses were relatively small 1, 2. In other words, the results of these trials depended on the magnitude of the response to the placebo, as well as the response to the active drug.

These findings suggest that the placebo response may also influence the results of other types of trials. A comparison between a drug in pill form and a device or surgery would be subject to a similar effect if, for example, the overall response to a device or surgery includes a greater placebo component than does the pill to which it is compared. Under such circumstances, a difference between two treatments might result from differences in their placebo effects rather than differences in the therapies themselves. If the placebo can influence the outcome or interpretation of a therapeutic trial in this way, it is important to determine what factors may modify the “placebo dose” and ask if different sham controls have different effects.

It is generally accepted that the strength of a drug placebo's response is related to its route of administration. In 1955, Louis Lasagna, an early investigator of the placebo effect, noted that “an injection is thought to be more effective than something taken by mouth” [3]. And it was said that “for universal patient acceptance nothing can approach the psychotherapeutic impressiveness of puncture of the integument by a hollow needle. The placebo substance introduced via the needle is usually second in importance to the needle stick [itself]” [4].

The notion of an “enhanced” [5] or “mega-placebo” [6] effect is probably applicable to interventions such as surgery or devices, if, as claimed, the placebo effect is influenced by elaborate rituals [7], appeals to mysterious powers [8], or high technology [9]. Indeed, acceptance of an enhanced placebo effect underlies the opinion that practicing physicians may “choose treatment whose appearance or route of administration is known to be associated with strong placebo effects” [10]. But do we know whether heightened placebo effects actually exist? As Lasagna states, “the art of the placebo” is “based not on any systematic investigation of the facts but on impressions” [3].

This article examines the evidence for the existence of an enhanced placebo effect for devices and discusses its implications for the design and interpretation of clinical trials. A heightened placebo effect may be particularly influential in determining the outcome of trials that compare a device either to a sham device or to a pill, or trials that compare a surgical procedure to medical management.

Section snippets

Evidence for an enhanced placebo effect

The documentation of an enhanced placebo effect is based on both direct evidence and meta-analysis. While some placebo research is recent, much of what is described below was performed between the mid-1950s and the late 1960s when the widespread adoption of the double-blind placebo-controlled RCT called attention to the significant effects of the placebos (and attempted to remove its distorting influence) [11]. This early period of placebo inquiry ended when the ethical requirement for patient

Implications of an enhanced placebo effect

Although scientific evidence for an elevated placebo effect remains inconclusive, it is worth considering the potential implications of such a phenomenon. Indeed, failure to do so in the past may well have contributed to errors in the design of some RCTs and misinterpretations of the results of others.

The most important implications of an enhanced placebo effect relate to the tendency to ignore how the placebo baseline may influence the results of an RCT. In the placebo-controlled RCT,

Designing studies to elucidate an enhanced placebo effect

It seems clear that the demonstration of an enhanced placebo effect would have a large impact on the interpretation of many completed RCTs and on the design of new ones, particularly those involving a comparison of two different types of therapeutic modalities. Were it not for ethical constraints, one might hope to demonstrate an enhanced placebo effect simply by conducting a RCT that compares the effects of a sham device and an oral placebo pill. A more ethically acceptable trial, however,

Conclusion

The evidence for the existence of an enhanced placebo effect for devices and procedures is intriguing but by no means conclusive. Most studies on the subject were conducted before the era of obligatory informed consent and suffer from methodological flaws that cast doubt on their validity. Yet, the phenomenon cannot be ignored because its existence has important implications for the interpretation of many influential RCTs. Suggestions have been made for how the enhanced placebo effect might be

Acknowledgements

This study was supported in part by the John E. Fetzer Institute, Kalamazoo, Michigan. The criticism and feedback of Charles Berde, MD, PhD, David Eisenberg, MD, Herman Engelburt, MD, Rose Goldman, MD, David Hoaglin, PhD, Catherine Kerr, PhD, and Sidney Klawansky, MD was especially valuable in developing this paper. We also thank the Seminar on Effective and Affordable Health Care at Harvard University for allowing a presentation of an earlier version of this paper. The research assistance of

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