Placebos that harm: sham surgery controls in clinical trials.

Alex John London,Joseph B Kadane

doi:10.1191/0962280202sm300ra

Alex John London, Joseph B Kadane

Open Access

https://doi.org/10.1191/0962280202sm300ra

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Abstract

Recent debates over the use of sham surgery as a control for studies of fetal tissue transplantation for Parkinson's disease have focused primarily on rival interpretations of the US federal regulations governing human-subjects research. Using the core ethical and methodological considerations that underwrite the equipoise requirement, we find strong prima facie reasons against using sham surgery as a control in studies of cellular-based therapies for Parkinson's disease and more broadly in clinical research. Additionally, we believe that these reasons can be generalized to apply to the use of other placebo controls that carry significant risks of positive harms in and of themselves. As a result, our arguments are centrally relevant to the emerging drive to subject therapies with a surgical component to the same rigorous standards of evaluation as those governing the approval of new pharmaceuticals.

Highlights

Responsible and scienti cally sound human-subjects research seeks to advance the state of medical knowledge and clinical practice without knowingly compromising the welfare and integrity of individual trial participants in the process
We argue that the use of sham surgery in clinical research raises fundamental questions about the goals of human-subjects research and the best ethical and methodological framework for evaluating research protocols
As long as the risks associated with the sham surgery have been minimized as far as possible without vitiating the integrity of the trial design, and the remaining risks are reasonable in relation to the value of the knowledge to be gained from the study, sham surgical controls are on a par with other nontherapeutic elements of a clinical trial that may pose some degree of risk to participants

Summary

Introduction

Responsible and scienti cally sound human-subjects research seeks to advance the state of medical knowledge and clinical practice without knowingly compromising the welfare and integrity of individual trial participants in the process. In its most basic formulation, equipoise represents a state of genuine and credible doubt about the relative therapeutic merits of some set of interventions that target a speci c medical condition, and to many it represents a necessary condition for ethically acceptable human-subjects research.[6,7,8] To some degree, the relative inattention to equipoise in this debate no doubt re ects the fact that it does not have the same regulatory status as the rules articulated in the federal regulations It may re ect ongoing uncertainties about the best way to explicate the concept of equipoise itself. We elucidate some of the conditions that would have to be obtained to override these prima facie reasons

Sham surgery and the current US regulatory framework

The purpose of clinical trials

Sham surgery and the principle of equipoise

Active placebos in drug trials

Findings

Conclusion