All in Our Heads? The Power of Placebo Response


Applied Clinical Trials

Applied Clinical TrialsApplied Clinical Trials-04-01-2018
Volume 27
Issue 4

Lisa Henderson discusses randomized clinical trials with active and non-active placebo treatments.

How often do you actually think of the mechanics behind a randomized clinical trial? For having a control group

Lisa Henderson

that receives a placebo vs. the group receiving the investigational compound? We know that in certain trials, for example, such as oncology, the randomized clinical trial doesn’t mean these patients are getting a non-active placebo, but receive either a current treatment therapy or standard of care treatment. 

For Duchenne muscular dystrophy, one family had two sons with the disease. One was able to enter a trial for a Sarepta Therapeutics drug, but the other child was too sick to receive it. In that case, the parents noted such marked positive response in receiving the treatment, they were anxiously awaiting that drug’s subsequent approval so their other son could receive it.

That’s not a true case of a placebo response in a randomized clinical trial, but a clear example of positive response on a drug. 

In a recent webinar from Premier Research (, it offered a comprehensive overview of placebo, with a specific focus in chronic pain trials. Webcast speakers referred to the etymology of the word placebo. Basically, a Latin word, which meant “to please.” It received a negative connotation when, in later centuries, paid mourners attended funerals to sing the praises of the dead, without having known the person. They were called placebos, and, thus, people who deceived.

In clinical trials, placebos are designed to “deceive” both patients and investigative staff to look the same as the investigational medicine. And randomization is a process to make sure that no one at the site level is sure who received the placebo or the active compound. Randomization and data privacy at this level is very complex, but there is more to placebo than placing people behind a data identifier. And this became clear in the webcast.

For example, patients with chronic pain are used to seeing one physician and form relationships with those physicians and their staff. In these cases, it’s best that if a patient is in a study at the same center, they see different people and research staff. These staff will be trained to make sure all patients are evaluated in the same manner, that they adopt a very objective speaking style with the trial participant, and they received appropriate response training. The speakers called this “objective staffing.” 

The speakers also noted the placebo effect, by where the patient wants “to please” their doctor or staff by “giving” them the appropriate response. Conditions that are self-reported and subjective in their assessments are the most impacted by the placebo effect. As such, the objective training is essential in lowering the placebo response.

Another issue is sometimes, based on increased medical attention in a trial or by virtue of believing they are receiving an actual medication, people feel better. 

Unfortunately, the placebo response has led to the failure of large clinical programs, with prior clinical efficacy, due to the inability to separate from a high placebo response. As sponsors work to address different options beyond opioids to manage pain therapies, clear strategies that address placebo response become very important. 


Lisa Henderson is Editor-in-Chief of Applied Clinical Trials. She can be reached at Follow Lisa on Twitter: @trialsonline

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