Is Placebo Surgery Unethical?

Horng, Sam; Miller, Franklin G.

doi:10.1056/nejmsb021025

Cited by 155 publications

(74 citation statements)

References 18 publications

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“…The use of sham control subjects for interventional procedures poses risks to research subjects without the prospect of direct benefit from participation in trials (21). However, as previously demonstrated (22,23), a well-conducted sham-controlled study, in which subjects have been adequately informed, is justified (24).…”

Section: Discussionmentioning

confidence: 98%

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma

Castro

Rubin

Laviolette

et al. 2010

Am J Respir Crit Care Med

624

289

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Rationale: Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. Objectives: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting b 2 -agonists. Methods: A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%). Measurements and Main Results:The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 6 1.10; sham, 1.16 6 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/ school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively).Conclusions: BT in subjects with severe asthma improves asthmaspecific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).Keywords: asthma; Alair Bronchial Thermoplasty System; bronchial thermoplasty; bronchoscopic procedure; Asthma Quality of Life Bronchial thermoplasty (BT) is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during a series of bronchoscopy procedures, resulting in a prolonged reduction in airway smooth muscle (ASM) mass (1, 2). Increased mass and contractility of ASM augments asthma morbidity by causing greater bronchoconstriction and airflow obstruction (3). Decreasing the amount and/or contractility of ASM may provide a means to ameliorate the symptoms of asthma.Previous clinical trials of BT were nonrandomized (4) or randomized to include a standard of care control group (5, 6). In these initial studies, BT was associated with a decrease in the AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Bronchial thermoplasty is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during a series of bronchoscopy procedures. What This Study Adds to the FieldThe current study reflects one of the largest shamcontrolled trials in pulmonary medicine to test a novel device to perform bronchial thermoplasty, a procedure for the treatment of ...

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Section: Discussionmentioning

confidence: 98%

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma

Castro

Rubin

Laviolette

et al. 2010

Am J Respir Crit Care Med

624

289

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“…This objection is not valid, however, because it conflates the ethics of clinical care with the ethics of clinical research. 9,18 Whereas the aim of clinical care is to maximize the health and well-being of particular patients, the goal of research is to acquire clinically relevant knowledge that will benefit future patients. 9 In clinical research, there is no requirement to offer participants the prospect of direct benefit or to ensure the absence of risk.…”

Section: Methodological Justificationmentioning

confidence: 99%

“…9,18 Whereas the aim of clinical care is to maximize the health and well-being of particular patients, the goal of research is to acquire clinically relevant knowledge that will benefit future patients. 9 In clinical research, there is no requirement to offer participants the prospect of direct benefit or to ensure the absence of risk. Indeed, critical areas of biomedical research, including Phase I toxicity testing and studies of pathophysiology, expose participants to risk without the prospect of direct benefit.…”

Section: Methodological Justificationmentioning

confidence: 99%

Placebo-Controlled Procedural Trials for Neurological Conditions

Horng

Miller

2007

Neurotherapeutics

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Summary:Neurological disease has been a central focus in the ongoing ethical debate over the use of invasive placebo controls, especially sham surgery. The risk to research subjects and necessary use of deception involved in these procedures must be balanced against the methodological need to control for bias and the placebo effect. We review a framework formulated for the ethical assessment of sham surgery in the context of research evaluating novel procedures for neurological conditions. Special issues raised include the growing evidence of expectation and conditioning effects in a number of neurological diseases, the escalating scale of risk from different types of invasive placebo interventions, and the increasing use of cross-over designs, which allow a switch from placebo to active intervention without additional procedures.

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“…The ethical use of placebos in risky clinical trials is a matter of heated controversy (Macklin, 1999;Weijer, 2002;Horng and Miller, 2002;London and Kadane, 2002;Miller, 2003;Polgar and Ng, 2005). Because of their inability to fully participate in making autonomous choices, when the research subjects are children the use of placebos raises even more ethical concerns (Flynn, 2003;Miller et al, 2003;Derivan et al, 2004;Lynch, 2007;Martin and Robert, 2007;Morton, 2008).…”

Section: Placebo Usementioning

confidence: 99%

When Ethics Constrains Clinical Research: Trial Design of Control Arms in “Greater Than Minimal Risk” Pediatric Trials

2011

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For more than three decades clinical research in the United States has been explicitly guided by the idea that ethical considerations must be central to research design and practice. In spite of the centrality of this idea, attempting to balance the sometimes conflicting values of advancing scientific knowledge and protecting human subjects continues to pose challenges. Possible conflicts between the standards of scientific research and those of ethics are particularly salient in relation to trial design. Specifically, the choice of a control arm is an aspect of trial design in which ethical and scientific issues are deeply entwined. Although ethical quandaries related to the choice of control arms may arise when conducting any type of clinical trials, they are conspicuous in early phase gene transfer trials that involve highly novel approaches and surgical procedures and have children as the research subjects. Because of children's and their parents' vulnerabilities, in trials that investigate therapies for fatal, rare diseases affecting minors, the scientific and ethical concerns related to choosing appropriate controls are particularly significant. In this paper we use direct gene transfer to the central nervous system to treat late infantile neuronal ceroid lipofuscinosis to illustrate some of these ethical issues and explore possible solutions to real and apparent conflicts between scientific and ethical considerations.

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Is Placebo Surgery Unethical?

Cited by 155 publications

References 18 publications

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma

Placebo-Controlled Procedural Trials for Neurological Conditions

When Ethics Constrains Clinical Research: Trial Design of Control Arms in “Greater Than Minimal Risk” Pediatric Trials

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