Experimental Pain Variability May Predict Response to Drug vs Placebo in Clinical Trials

Experimental pain variability in clinical trials may be more accurate at predicting response to treatment vs placebo.

Experimental pain variability in clinical trials may be more accurate at predicting response to treatment vs placebo, according to a study in patients with knee osteoarthritis (OA), published in Pain.

Individuals with knee OA with symptoms lasting ≥6 months and pain intensity ≥4 on a 0 to 10 numeric rating scale were enrolled in this study (n=50). For the week-long treatment period, participants were given naproxen 250 mg twice a day for 3 days, naproxen 500 mg twice a day for 3 days, and naproxen 500 mg on the morning of the last treatment visit. Patients were randomly assigned to receive naproxen or placebo during the treatment period, which was followed by a washout period and by a second treatment period.

Current pain scores were assessed using the Staircase-Evoked Pain Procedure at baseline and at the end of each treatment period. Scores on the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale, as well as self-reported diary entries of daily pain scores and in-clinic pain scores, were collected. The investigators evaluated the association between the Focused Analgesia Selection Test, which measures pain-reporting variability in blinded patients in response to external thermal stimuli, and response to treatment.

There was a moderate linear relationship between variability of clinical and experimental pain reports (correlation factor, r=−0.416; P =.004). Clinical and experimental pain reports were also found to correlate with the placebo response (r=0.393 [P =.004] and r=−0.371 [P =.009], respectively). The Focused Analgesia Selection Test was the only assessment that was found to predict the treatment effect difference between naproxen and placebo (P =.002).

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The lack of data on the duration of chronic pain and pain-related measures represent potential limitations of the study.

“In summary, the results of the current investigation support a previously proposed model where patients whose attention is externally directed do not perceive or report bodily sensations accurately, are more vulnerable to external cues (such as placebos), and should either be excluded from clinical trials or trained to accurately report what is being measured in the study,” the investigators concluded.

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Treister R, Honigman L, Lawal OD, Lanier RK, Katz NP. A deeper look at pain variability and its relationship with the placebo response: results from a randomized, double-blind, placebo-controlled clinical trial of naproxen in osteoarthritis of the knee [published online February 25, 2019]. Pain. doi:10.1097/j.pain.0000000000001538