Results from a recent study that systematically analyzed the data of placebo-controlled trials in patients with BPH confirm that BPH is a progressive disease on the basis of worsening prostate volume, maximum urinary flow, and symptom score, as well as the rate of prostate-related surgery and acute urinary retention.
Berlin-Results from a recent study that systematically analyzed the data of placebo-controlled trials in patients with BPH confirm that BPH is a progressive disease on the basis of worsening prostate volume, maximum urinary flow, and symptom score, as well as the rate of prostate-related surgery and acute urinary retention.
Dr. Djavan and his colleagues performed a meta-analysis of more than 1,700 studies to assess what the true heterogenicity of placebo arms is and how placebo arms reflect the natural history of BPH. A total of 16 randomized, placebo-controlled trials were eligible for inclusion in the meta-analysis. These trials contained data on 12,158 men, mean age 62.6 to 66.5 years, from centers primarily in North American and Europe, and had a duration of 12 to 48 months. Mean baseline prostate volume of the patients was between 33.9 mL and 61.0 mL.
According to Dr. Djavan, the results reflect considerable heterogenicity of the different placebo arms, even in randomized, evidence-based level I studies.
"If we today judge our drugs based on a placebo, we must understand that these placebos are highly variable, not only because of the inclusion criteria, but also because of the study designs and by the natural heterogenicity of the placebo arm itself," Dr. Djavan asserted. "We were not able to compare the natural history of untreated BPH with placebo arms. The reason for this was that the placebo arms were far too heterogenetic to be compared. In other words, one has to really doubt any placebo-controlled trials done today."
Questioning placebo data
Dr. Djavan's assessment of the quality of data from placebo-controlled trials touched a nerve.
"Your last statement has to be a little controversial," said J. Curtis Nickel, MD, professor of urology at Queen's University, Kingston, Ontario, Canada. "That is a really strong statement based on the data you presented."
"I believe that when you look at the placebo-controlled trials, you have one drug that has a given function, and when you compare that to a placebo, the problem is not the true drug; the problem is the placebo," Dr. Djavan responded. "The placebo impact is so variable that we cannot actually judge the real impact of the true drug. In other words, the placebo arms and inclusion criteria are so variable in current studies that one has to doubt any conclusions drawn from randomized controlled trials."