The effectiveness of clinical research hinges on securing trust and transparency between researchers and trial participants. One of the arenas that can sometimes garner scrutiny in medical research and jeopardize trust between researchers and trial participants is the use of placebos in clinical trials.
When you want to participate in a clinical trial, you may be hesitant to consider participating in placebo-controlled trials. However, knowing the truth about placebo-controlled studies and how they can be an effective and ethical way to advance clinical research is important.
What Is a Placebo?
A placebo is a false medical treatment or intervention sometimes used in clinical research. A placebo may closely resemble the treatment being researched–enough that it is impossible to determine whether you’re receiving the actual or “fake” treatment.
What Is the Placebo Effect?
The “placebo effect” concept can be polarizing, especially for patients. The placebo effect refers to the perceived effect of a placebo intervention. For example, you may feel improvement in your condition after taking a pill, even if it is a placebo. This would be considered a “placebo effect.”
Placebo effects can also work oppositely. For example, if you dislike taking medications, and your doctor puts you on a medication that you have to take every morning, you may develop a negative or depressed mood as a result. Even if that medication turns out to be an inactive or nonfunctional placebo, you may report to your doctor that the pill caused you to have a depressed mood. This side effect, then, would be a placebo side effect—it was not directly caused by the medicine itself but by other variables, such as the mere ritual of taking the medicine.
Clinical researchers have to differentiate between the potential placebo effects that may be inherent within a study and the true activity and effectiveness of their interventional therapies. This way, they can ensure that treatments are effective on their own, and they don’t risk subjecting patients to active medications that are non-superior to placebos but have real side effects.
Understanding Clinical Trial Placebo Usage
If your doctor prescribes you a new medication, one of the first questions you may have is whether or not the new medicine will work. You may also wonder about the side effects of the new medicine. In reality, both of these questions pertain to how your current state, without the medicine, will compare to your future state with the medicine. Both of these considerations also scratch at the surface of why researchers use placebos in research trials. It is sometimes scientifically necessary to use placebos in research to establish treatment efficacy and safety.
What Is a Placebo Group?
A placebo group, or a placebo arm, of a clinical trial is a group of study participants who do not receive the intervention being studied. Instead, they may receive a pill that resembles, or is identical to, the intervention in appearance but does not perform an active medical function.
What Is Placebo Allocation?
When researchers design a study, they are highly concerned with making sure that their research is free of bias. In the most stringent types of clinical research trials, which are known as double-blinded, randomized controlled trials (RCTs), participants are randomly placed or allocated into groups. Placebo administration is sometimes used to test a new drug’s safety and effectiveness against a control group that does not receive the treatment but instead receives a placebo.
What Is a Placebo Response?
A placebo response measures how a study participant who receives a placebo intervention responds to the treatment. Measuring a placebo response can be a helpful way of determining whether a new drug or therapy makes a difference in health outcomes or whether the reaction is purely coincidental or inconsistent. For example, if a certain percentage of trial participants who received a placebo drug for depression report lower levels of depression over three months compared to the trial participants who received the actual medication, it can help researchers determine that the treatment drug is not effective.
When Are Placebo-Controlled Trials Used?
Placebo-controlled trials are heavily regulated and only permitted when they will not negatively affect a patient’s welfare. For example, if you have a known blood clot in your leg and you are participating in a clinical trial investigating the effectiveness of a new blood thinner, it would not be safe to take you off blood thinners, allocate you to a placebo arm of the study, and compare you to people who are receiving blood thinners. A placebo-controlled trial will never jeopardize patient safety in this way.
Instead, placebo-controlled trials can be used to evaluate the efficacy of a new drug or intervention compared to a baseline state of not having an available intervention. For example, if there was a new disease that started turning people’s hair green, and researchers developed a topical cream to reverse this process, there is no existing cream available to use as a comparison. Comparing the new cream against a placebo cream would not be dangerous to those not receiving the drug, as they would not have any alternative treatment options available and would be at their baseline state.
However, using a placebo cream as a comparison in this scenario would help researchers determine whether the condition may improve spontaneously without any intervention (which would be the case if people using the treatment cream had the same rate of improvement as the people using the placebo cream), whether the new cream is effective, and whether it has any side effects.
Ethical Considerations in Placebo-Controlled Trials
It’s important to remember that not every randomized, double-blinded controlled trial uses a placebo. Often, new treatments are compared to the standard of care, which could be another existing drug. Researchers do not use placebos to investigate drugs that have known, proven treatments (for example, placebos are rarely used in clinical trials for cancer patients). For studies that use placebos, several ethical considerations are involved when researchers design a placebo-controlled trial.
- If a study design includes a placebo, researchers are required to inform clinical trial participants in advance of their participation that a placebo will be used. This disclosure happens during a critical step known as informed consent.
- During the study, participants will not know if they received the placebo or investigative treatment. This helps keep the research free from bias.
- During the study, researchers will often be blinded about who has received a placebo and who has not—this is an additional safeguard against bias.
- If a placebo is found to be an effective therapy as a result of the study, the people in the placebo arm will also be offered the non-placebo treatment.
The bottom line on the use of placebos in clinical trials is that they ensure that research is rigorous and oriented around developing new, effective, safe treatments. As a trial participant, you will never be included in a placebo-controlled trial without being informed of this. You will be offered the alternative therapy if you are in the placebo arm, and the research ultimately shows that the treatment being studied was effective compared to the placebo.
How To Learn More About Clinical Trial Methodology
The clinical trial design teams at M3 Wake Research are committed to advancing medicine through double-blind studies to improve the lives of current and future generations. With nearly four decades of industry experience, M3 Wake Research excels at improving all health care through randomized controlled trials, including participant blinding.
Interested in joining a study or want to learn more? View a list of our currently enrolling studies.