A randomized, double-blind, and placebo-controlled trial is the best type of clinical research.
Even a well-designed study can lead to questionable conclusions. One example is the REDUCE-IT cardiovascular study that was recently followed up. Although many clinical trials focus on innovative treatments, it is essential to choose a placebo.
This study was a success because of its power.
This type of study involves randomly assigning subjects to one of two groups. One group receives the new drug being tested, while the placebo group is given a fake treatment.
Researchers and study subjects need to be aware of who is getting active treatment and who is being given a placebo. They are blind to group assignments, which is why double-blinding is used. The treatment assignment is either coded and kept secret at the end of the study or decoded at planned intervals earlier to ensure safety or effectiveness.
This decreases the likelihood that participants or researchers will have biased results. This means that side effects or health differences can be reasonably attributed to treatment.
What you need to know about placebo therapy
Researchers and study participants should not be able to tell which patient is receiving active treatment and which is being given a placebo. Sometimes, however, participants may be able to identify what treatment they received. One example is that active treatment may have a bitter taste or side effects such as diarrhea.
This means that the study will not be double-blind. Expectations could have an impact on the outcome. This can be assessed by asking participants whether they believed they received active treatment or a placebo during and after the trial. Blinding is successful if the answers are inconsistent or the subjects respond, “I don’t know.”
Although a placebo treatment should not have any effect, it is sometimes true.
- The well-known placebo effect, a positive result related to an expectation of benefits, can be described as a positive effect. If you tell someone that a pill can relieve their pain, they will feel relief, even if it is just a placebo.
- The nocebo effect is a negative side effect of a placebo. If you tell someone they may get diarrhea from taking the placebo pill, it could cause them to experience this. If the placebo was used in another study, it might cause headaches.
A placebo should not have any biological effect on the person taking it. This is where REDUCE-IT went wrong.
REDUCE-IT illustrates the importance of carefully choosing a placebo
REDUCE-IT, also known as the Reduction Of Cardiovascular Events With Icosapent Ethyl Intervention Trial, is the full name. This trial was created to test whether icosapent Ethyl could lower triglyceride levels to decrease cardiovascular diseases such as stroke or heart attack.
Triglycerides, a type of fat found in the blood, are an example. Experts aren’t sure if lowering triglyceride levels will result in fewer strokes or heart attacks, although high levels can increase cardiovascular risk.
Participants who took the active drug saw a drop in triglyceride levels. The rates of cardiovascular problems such as stroke or heart attack were 25% lower in participants who received the active drug than those who received a placebo. Even more cardiovascular deaths were prevented in the treatment group by 20%.
These findings led to FDA approval of a drug label claiming that icosapent-ethyl benefits individuals at high risk of developing cardiovascular disease.
Soon after the publication of the study in 2019, questions emerged. The treatment group did better than the placebo. However, careful analysis of the results indicated that the placebo group suffered more strokes and heart attacks over time than the treatment group.
Another study confirms the results.
The study’s authors responded to these questions and performed additional analyses. They also looked at biomarkers in blood that are associated with cardiovascular risk. Participants who received the active drug showed little difference in biomarker results. However, biomarkers were worse in the placebo group. This suggests that the apparent benefit conferred on the drug might have been due to the adverse effects of a placebo!
What could make a placebo increase cardiovascular risk? One possibility is that the placebo mineral oil may have decreased the absorption of statin drugs participants were using to lower cholesterol. This can also impact heart and blood vessel health. This new analysis shows that there was some truth to the skeptical reaction to the initial study’s dramatic results. Additional research is needed.
The bottom line
This story has three main points for me:
- Research can lead to flawed conclusions in many different ways. Though it seems unlikely, this unfortunate placebo choice is a possible one.
- Medical research must be open to criticism and reassess findings if needed.
- This self-correction process has worked in the REDUCE-IT case.
The initial 2019 study was successful, and enthusiasm for the drug icosapent-ethyl was high. However, this excitement may recede following the latest analysis. One thing is sure: science isn’t unable to make a decision, as it is often said. Science is supposed to be able to reassess and correct when necessary.
