Meta-Analysis Determined Placebo Response in RCTs for Painful Diabetic Neuropathy

To characterize placebo and nocebo responses in placebo-controlled randomized clinical trials of oral drug treatments for painful diabetic neuropathy (PDN), an international team of researchers conducted a systematic review of the medical literature and a meta-analysis of the data it contained and published their findings in Pain.

The researchers searched 4 databases for trials with a parallel-group design of oral drugs for PDN published in the last 20 years and evaluated the magnitude of the placebo or nocebo responses, Cochrane risk of bias, heterogeneity, and moderators of the 21 trials they identified, which together included 2425 placebo-treated patients.

The overall mean pooled placebo response was a -1.54 change in pain intensity from baseline with a moderate effect size. The pooled placebo 50% response rate was 25%. The percentage of patients with adverse events in the placebo arms was 53.3% and 5.1% of those patients dropped out due to these events.

The year of study initiation was the only significant moderator of placebo response. More recent trials tended to be longer and bigger and to include older patients.

“Our findings confirm the magnitude of placebo and nocebo responses, identify the year of study initiation as the only significant moderator of placebo response, draw attention to contextual factors such as confidence in PDN treatments, patients’ previous negative

experiences, intervention duration, and information provided to patients before enrollment,” the study authors wrote.

Study limitations include the absence of a study arm in which participants received no treatment in the trials analyzed, which prevented effects from being controlled for confounding factors such as the natural history of the disease and regression to the mean. In addition, the study’s statistical analysis was not adjusted for multiple comparisons, and data at the level of the individual patient was not available to the researchers.

This article originally appeared on Clinical Pain Advisor