The Power of Placebo in Alzheimer's Disease Research - Alzheimer's Prevention Bulletin | Alzheimer's Prevention Registry

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May 15, 2017

The Power of Placebo in Alzheimer's Disease Research - Alzheimer's Prevention Bulletin

By Alzheimer's Prevention Bulletin

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It was more than 20 years ago that William J. Burke, MD, Director of the Stead Family Memory Center at Banner Alzheimer’s Institute, first experienced the power of placebo.

He wanted to measure the impact of a certain drug on inflammation in the body. When he contacted the Food & Drug Administration (FDA) about the study, they suggested he include a placebo group in the study. 
“I thought we would do an observational study and measure if the drug benefitted the participants,” he said. “But, the FDA had a good point by wanting me to include a small placebo group so that’s what we did.”

Toward the conclusion of the six-month study, a colleague working with Dr. Burke on the study reported that several of the participants seemed to be doing particularly well. 

“At the end of the study, we broke the blind and learned who was taking the drug and who was taking the placebo,” Dr. Burke said. “It turned out the people who were doing really well were the people taking the placebo.”

Dr. Burke’s experience demonstrates the value of the seemingly simple placebo to research studies. 

“A placebo is a substance that looks like a regular treatment or medication but is not,” Dr. Burke said. “It can be a pill, injection, liquid or even a procedure.” 

Including a placebo group in a study allows researchers to compare the results of the group who received the actual treatment to the “comparison group” prescribed the placebo. It also increases the safety of studies and eliminates the expectation effect – both positive and negative – from those studies. 

“We don’t know that a particular new treatment is effective, so we have to compare it something, either a standard therapy or a placebo,” Dr. Burke said. 

 This notion is at the heart of medical research that is both ethical and effective. For example, if researchers knew the therapy they were studying was effective, it would be unethical to pursue a study. Or, if they knew the study would show the therapy was not effective, it also would be unethical for researchers to pursue a study.

High Expectations

Researchers understand that people participating in a study may have expectations about what is going to happen. Known as the placebo effect, study participants taking placebo may have a positive change in their symptoms if this is what they expect will happen. 

Study participants also may experience the nocebo effect. About 25 percent of study participants who believe they’re receiving a powerful study medicine, but are actually taking a placebo, report side effects. When asked by a researcher involved in their study, 27 to 71 percent will say they’re having side effects.

Both study participants as well as researchers may experience the expectation effect.

“The researcher, for example, may believe the treatment is really going to work and unintentionally assign people who are healthier to the group receiving the actual study medicine,” said Dr. Burke. “The people who are less healthy would then be assigned to the compare or placebo group. This would compromise the outcomes.”

 Research studies can control these effects by:

  • Incorporating a placebo to learn if the study drug works as well as to learn its side effects. 
  • Using a method to randomly assign study participants to either the group that will receive the treatment that’s being tested or the placebo group.
  • Designing “double blind” studies so neither the researchers nor the study participants know who is receiving the treatment being tested or the placebo.

Careful Monitoring

According to Dr. Burke, double blind studies control the expectation effect by allowing researchers to simply record data. Data Monitoring Committees – doctors, statistical experts, researchers and others – who work independently of the study’s research team review this data and oversee the study’s progress. 

What do Data Monitoring Committees look for in these reviews? 

“They search for unusual side effects or side effects that have not been reported previously,” said Dr. Burke.

If the data shows very positive results, the Data Monitoring Committee may recommend stopping the study early so the treatment can move to the next level. They also could stop the study if they find it’s statistically impossible for the treatment being studied to reach a positive conclusion.

“This is a particularly important feature because a lot of the studies we’re doing now – particularly Alzheimer’s disease prevention studies – go on for years,” Dr. Burke said. “We need that periodic external analysis to make sure the study medication is safe and the study can reach an outcome, whether that’s positive or negative.”

Listen to Dr. Burke speak more about his experiences with placebo and research studies by watching StudyTalks: The Power of Placebo in Alzheimer’s Research.

You also can learn about prevention studies at the Alzheimer Prevention Registry.