ABSTRACT The ethical aspects of placebo control in clinical trials have been extensively and controversially debated in the last decade. However, a thorough analytical comparison of the different existing international regulations, their terminologies and their ethical principles concerning placebo, is still missing. The central issue in the ongoing controversy is the justification of placebo‐use, if proven treatment exists. All present versions of the examined guidelines propose such justifications, but each guideline differs from the others in relevant details. Therefore the conditions (...) justifying placebo‐use according to each guideline are the focus of our attention. We will first propose a formalized general principle that defines the ethical acceptability of placebo‐use. Then we will analyse three categories of conditions put forward by the different documents: the risk of harm or burden, compelling scientific reasons, and the availability of proven treatment. The analysis shows important normative discrepancies and contradictions between the examined guidelines. Especially striking is the fact that some guidelines allow the participants in clinical trials to be exposed to a risk of serious harm, while others do not. Finally, we try to show how the normative difference of each guideline could influence the decision of researchers or IRBs concerning the ethical acceptabililty of placebo‐use. (shrink)

This book examines the controversies surrounding biomedical research in the twenty-first century from a human rights perspective, analyzing the evolution and ...

The ethical aspects of placebo control in clinical trials have been extensively and controversially debated in the last decade. However, a thorough analytical comparison of the different existing international regulations, their terminologies and their ethical principles concerning placebo, is still missing. The central issue in the ongoing controversy is the justification of placebo‐use, if proven treatment exists. All present versions of the examined guidelines propose such justifications, but each guideline differs from the others in relevant details. Therefore the conditions justifying (...) placebo‐use according to each guideline are the focus of our attention. We will first propose a formalized general principle that defines the ethical acceptability of placebo‐use. Then we will analyse three categories of conditions put forward by the different documents: the risk of harm or burden, compelling scientific reasons, and the availability of proven treatment. The analysis shows important normative discrepancies and contradictions between the examined guidelines. Especially striking is the fact that some guidelines allow the participants in clinical trials to be exposed to a risk of serious harm, while others do not. Finally, we try to show how the normative difference of each guideline could influence the decision of researchers or IRBs concerning the ethical acceptabililty of placebo‐use. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best methods will (...) favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, “best proven diagnostic and therapeutic method” that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for (...) suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls. (shrink)