The success of placebos in managing chronic pain may be why so many clinical trials for drugs to treat pain fail, a new study suggests.
For a new study, researchers analyzed the results of 84 clinical trials of drugs conducted around the world from 1990 to 2013. Over that period, the pain inhibition experienced by patients taking a placebo continued to rise, reaching an average 30 percent decrease in pain levels by 2013.
Similar increases in placebo response have previously been observed in studies of clinical trials of antidepressants and antipsychotic drugs.
Surprisingly, however, the analysis of clinical trials found that the increase in placebo responses occurred only in trials conducted wholly in the United States. Trials conducted in Europe or Asia showed no changes in placebo responses over that period.
Researchers examined reported features of the clinical trials to determine what factors might be responsible for the changes over time.
They found that in the US, but not elsewhere, trials are becoming longer (from an average of four-weeks long in 1990 to 12 weeks in 2013) and larger (from an average of fewer than 50 patients in 1990 to an average of more than 700 patients in 2013). Senior author Jeffrey Mogil, professor of pain studies at McGill University, said:
“The data suggest that longer and larger trials are associated with bigger placebo responses. This, in turn, tends to result in the failure of those trials—since it makes it harder for pharmaceutical companies to prove that the drug being tested is more effective than treatment with a placebo.”
Adds Alexander Tuttle, a doctoral student in psychology and co-first author of the paper:
“It remains to be determined why the United States is an outlier with respect to its clinical trials.”
The researchers note, however, some potentially important differences between the US and other countries, including the existence of direct-to-consumer drug advertising in the US (New Zealand is the only other country in the world that allows this), the greater spread of for-profit “contract research organizations” in the US, and perhaps greater exposure to the placebo concept in popular media.
“The greater the improvement in patients treated with placebo in clinical trials, the more difficult it can be to demonstrate the beneficial effects of pain-relieving medications,”
says Robert H. Dworkin, professor of anesthesiology, neurology, and psychiatry at the University of Rochester, who was not involved in the study.
“This important study increases our understanding of these placebo-group responses, and thereby provides a basis for improving the design of clinical trials and accelerating the development of analgesic medications that can bring greater relief to patients suffering from chronic pain.”
Tuttle, Alexander H.; Tohyama, Sarasa; Ramsay, Tim; Kimmelman, Jonathan; Schweinhardt, Petra; Bennett, Gary J.; Mogil, Jeffrey S.
Increasing placebo responses over time in U.S. clinical trials of neuropathic pain
Pain, August 22, 2015 doi: 10.1097/j.pain.0000000000000333
Top Illustration: Damian Gadal/flickr