http://jme.bmj.com/content/35/6/384.short

J Med Ethics 2009;35:384-389 doi:10.1136/jme.2008.028357

• Research ethics

A renewed, ethical defense of placebo-controlled trials of new treatments for major depression and anxiety disorders

1. B W Dunlop1,
2. J Banja2

+ Author Affiliations

1. ¹

   Emory University School of Medicine, Atlanta, Georgia, USA
2. ²

   Atlanta Clinical and Translational Science Institute, Emory University School of Medicine, Atlanta, Georgia, USA

1. Boadie W Dunlop, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1256 Briarcliff Road NE, Building A, 3rd Floor, Atlanta, GA 30322, USA; bdunlop@emory.edu

• Received 18 November 2008
• Revised 30 January 2009
• Accepted 3 March 2009

Abstract

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. 

In V-Bi science the normal curve is used to determine efficacy of drugs along with their side effects. issues like whether patients can be denied medication when enrolled in trials can also be decided with normal curve statistics. One problem is that issues below a significance level can persist from drugs that pass trials, also that the structure of a trial can get a drug just over the 5% significance level it needs. There is then a minimum uncertainty between randomness appearing to be a good drug or one without side effects or chaos where deterministic variables are actively causing problems. These are referred two as Type 1 and Type 2 errors in statistics. 

It is possible however to have trials that are close to this significance level without any efficacy, for example withholding trials with poor results can bias the other trials so chance appears to be significant improvements in patients.    

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.