OJS  Vol.5 No.2 , April 2015
Misunderstanding of a New Approach to Drug-Placebo Difference Calculation in Short Term Antidepressant-Drug Trials
Author(s) Yanning Liu1,2
ABSTRACT
In clinical trials, drug effect is measured by a difference between subjects who are treated by experimental drug against placebo-treated subjects. In case of binary data, with observing YES/NO on each subject in certain period of time, it is the proportion of subjects who respond in treatment group minus the proportion of responders in placebo group (for example, 50% vs. 30%). However, a greater difference was proposed by Rihmer et al. (2011) [1] with their supporting arguments, in that antidepressant response and placebo response had different mechanisms and there were equal chances for antidepressant responder to be responding to placebo and not responding to placebo at all. Therefore, the authors proposed 50% - 30% * 50% when the response rate in the treatment group and the placebo group are 50% and 30% respectively, resulting in higher drug-placebo difference than traditional understanding of 50% - 30%. In this article, we tried to explain why the authors misunderstood the drug-placebo concept for evaluating drug superiority, their misunderstanding of assumptions of traditional calculation, as well as their wrong reasoning on their proposed approach. All in all, we conclude the traditional approach of 50% - 30% is the right way of evaluating drug-placebo difference and the possible methods to control impact of placebo effect are briefly discussed at the end of this article.

Cite this paper
Liu, Y. (2015) Misunderstanding of a New Approach to Drug-Placebo Difference Calculation in Short Term Antidepressant-Drug Trials. Open Journal of Statistics, 5, 113-119. doi: 10.4236/ojs.2015.52014.
References
[1]   Rihmer, Z., Gonda, X., Döme1, P., Erdos, P., Ormos, M. and Pani, L. (2011) Novel Approaches to Drug-Placebo Difference Calculation: Evidence from Short-Term Antidepressant Drug-Trials. Human Psychopharmacology: Clinical and Experimental, 26, 307-312.

[2]   Rihmer, Z. (2007) Drug-Placebo Difference: In Antidepressant Drug Trials Could Be 50% Greater Than Previously Believed. Neuropsychopharmacologia Hungarica, 9, 35-37.

[3]   Rihmer, Z. and Gonda, X. (2008) Is Drug-Placebo Difference in Short-Term Antidepressant Drug Trials on Unipolar Major Depression Much Greater Than Previously Believed? Journal of Affective Disorders, 108, 195-198.
http://dx.doi.org/10.1016/j.jad.2008.01.020

[4]   Johnson, M.R., Lydiard, R.B., Morton, W.A., Laird, L.K., Steele, T.E., Kellner, C.H., et al. (1993) Effect of Fluvoxamine, Imipramine and Placebo on Catecholamine Function in Depressed Outpatients. Journal of Psychiatric Research, 27, 161-172.
http://dx.doi.org/10.1016/0022-3956(93)90004-L

[5]   Carpenter, L.L., Anderson, G.M., Siniscalchi, J.M., Chappell, P.B. and Price, L.H. (2003) Acute Changes in Cerebrospinal Fluid 5-HIAA Following Oral Paroxetine Challenge in Healthy Humans. Neuropsychopharmacology, 28, 339- 347.
http://dx.doi.org/10.1038/sj.npp.1300025

[6]   Mayberg, H.S., Silva, J.A., Brannan, S.K., Tekell, J.T., Mahurin, R.K., McGinnis, S., et al. (2002) The Functional Neuroanatomy of the Placebo Effect. The American Journal of Psychiatry, 159, 728-737.
http://dx.doi.org/10.1176/appi.ajp.159.5.728

[7]   Leuchter, A.F., Cook, I.A., Witte, E.A., Morgan, M. and Abrams, M. (2002) Changes in Brain Function of Depressed Subjects during Treatment with Placebo. The American Journal of Psychiatry, 159, 122-129.
http://dx.doi.org/10.1176/appi.ajp.159.1.122

[8]   Enck, P., Benedetti, F. and Schedlowski, M. (2008) New Insights into the Placebo and Nocebo Responses. Neuron, 59, 195-206.
http://dx.doi.org/10.1016/j.neuron.2008.06.030

[9]   Scott, D.J., Stohler, C.S., Egnatuk, C.M., Wang, H., Koeppe, R.A. and Zubieta, J.K. (2008) Placebo and Nocebo Effects Are Defined by Opposite Opioid and Dopaminergic Responses. Archives of General Psychiatry, 65, 220-231.
http://dx.doi.org/10.1001/archgenpsychiatry.2007.34

[10]   Sharot, T., Riccardi, A.M., Raio, C.M. and Phelps, E.A. (2007) Neural Mechanisms Mediating Optimism Bias. Nature, 450, 102-105.
http://dx.doi.org/10.1038/nature06280

 
 
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