Is Placebo More Than Just a Feeling?

Placebo arms in randomized controlled trials are becoming increasingly popular to help control for the various nonspecific effects such as natural history, regression to the mean, and placebo effects.

A placebo effect can be distinguished as a physiological response to the therapeutic context of an intervention delivery, where a placebo response is classified as the improvement of participants in a placebo arm for any reason.

Is placebo more than just a feeling? by Cameron Faller

This is where we were led to believe that placebo effects had a particularly strong influence on subjective outcomes (i.e. pain), and therefore we could reduce placebo responses by utilizing objective markers as primary outcomes rather than patient-reported outcomes.

Since this has not been studied as extensively, five RCTs regarding rheumatoid arthritis were retrospectively extracted that were testing a drug trial against a placebo arm. Rheumatoid arthritis drug trials were included in part due to their assessment of patient reported pain levels as well as changes in objective biomarkers (C-reactive protein [CRP] levels or erythrocyte sedimentation rate [ESR]).

Results found that there were statistically significant decreases in both pain and objective biomarkers in all of the 5 RCTs.

It is believed that a majority of these decreases are dominated by natural history and regression to the mean, however, it is clear that placebo responses cannot be limited to a psychological effect alone.

The importance of this study suggests that investigators need to be aware of the natural history in relation to placebo arms and should not replace subjective outcomes with objective measures.

A variety of limitations existed with the biggest one including not involving a no-treatment group. Involving a pure control group where they did not get either the drug or placebo would have given us a better understanding of the true effects of natural history and regression to the mean.

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Via Dr. Cameron Faller's Instagram reposted with permission

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