Placebo design

Lotshaw, S., Bradley, R. and Brooks, L., Illustrating caffeine s pharmacological and expectancy effects utilizing a balanced placebo design. J Drug Educ 26(1), 13-24, 1996. 

Marlatt, G. Alan, and D. J. Rohsonow. 1 0. "Cognitive Processes in Alcohol Use Expectancy and the Balanced Placebo Design." In Advances in Substance Abuse, edited by Nancy K. Mello. Vol. 1. Greenwich JAI. 

Clinical trials should be designed so as to mirtimise potential sources of bias. It is known that patients can demonstrate a positive response to treatments that they believe will benefit them, even if no pharmaceutical agent has been admrrtistered (the placebo effect ). Similarly, investigators may be biased in their observations by an expectation of particular results. To avoid such bias, blinded trial designs are used. 

Appropriate study design should be selected to achieve the desired outcome. A description of the type/design of frial to be conducted (e.g., double-blind, placebo-controlled, parallel design) and a schematic diagram of trial design. 

Using a within-subject, placebo-controlled design, Haney et al. (2003) recently reported that nefazodone, an antidepressant that also has some sedative properties, decreased reports of anxiety and muscle pain during closely mon-... 

In the case of carbamazepine the evidence suggests that its prophylactic efficacy is less than that of lithium (Greil and Kleindienst, 1999). For valproate there is no placebo-controlled evidence as yet to support its efficacy in the prophylaxis of bipolar disorder. The only large-scale study designed to elucidate this action was a failed trial in which neither lithium nor valproate was more effective than placebo in maintenance treatment over 2 years (Bowden et al, 2000). 

ECASS-II was designed to test a lower dose of rt-PA (0.9 mg/kg) during the same 0-6-hours time period after stroke onset, using similar inclusion criteria as in ECASS-I. ° The primary endpoint was the proportion with a favorable outcome on the mRS scale (defined as a score of 0 or 1). There was no difference in this outcome between rt-PA-treated and placebo controls (40% vs. 37%, p = 0.28). A separate analysis of the 158 subjects enrolled within 3 hours of stroke onset also showed no difference in the proportion with a favorable outcome (42% vs. 38%, p = 0.63) this result, however, must be treated with caution because in ECASS-II there was a substantially lower number of patients treated within 3 hours of stroke onset, compared to the 1995 NINDS rt-PA study. Parenchymal hematoma on post-treatment CT was seen in 12% of rt-PA-treated and 3% of placebo patients (p < 0.001). The 90-day mortality rate was 11 % for the rt-PA group and 11 % for the placebo group (p = 0.54). Protocol violations were much less frequent in ECASS-II compared to ECASS-I (9% vs. 18%), probably because of standardized training in CT interpretation at the study sites. 

There are two main types of clinical trial design, parallel and cross-over. In a parallel study, subjects are assigned to one of two or more treatments, e.g. active and placebo, and proceed through the trial concurrently. In a cross-over design, subjects act as their own controls, undergoing two or more treatments in sequence (see Fig. 12.1). 

It is important that future studies of antioxidant treatment in patients with specific disorders should be well designed (randomized, double-blind, placebo-controlled) prospective studies that utilize the most up-to-date methodology to assess free-radical activity. 

A prospective, randomized, placebo-controlled trial of paroxetine in adults with chronic post-traumatic stress disorder (PTSD) was recently conducted (Marshall etal., 2007). The subjects were New Yorkers, predominantly female (67%) and Hispanic (65.4%). Seventy subjects entered the study and after a one week placebo lead-in, 52 subjects were randomized to placebo or paroxetine for ten weeks. The subjects were treated with a flexible dosage design (mean dosage, 40.4 mg/day). Dropout rates were 32% for paroxetine and 51.9% for placebo. There were no differences in rates of adverse effects between treatment arms. Paroxetine was superior to placebo in ameliorating the primary symptoms of PTSD (56% vs. 22.2%). 

This is a rather bleak picture of the effects of antidepressant treatment. In the best of circumstances - which is what the trial was designed to evaluate - only one out of three depressed patients showed a lasting recovery from depression, and since there was no evaluation of what the recovery rate might have been with placebo treatment, there is no way of knowing whether their recovery was actually due to the medication they had been given. 

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