The placebo effect is a phenomenon in which a person perceives an improvement in their condition or symptoms after receiving a treatment that has no therapeutic effect. This improvement is not due to the treatment itself but rather to the person’s belief in the treatment’s effectiveness. And the placebo effect is surprisingly powerful, especially for symptoms that are related to pain, sleep, and mood, as these can be psychosomatic in nature. Interconnected with the placebo effect is observation bias, which is when simply being observed in a study leads participants to change their behaviour. In clinical trials, participants may be more likely to eat healthier, better adhere to management strategies, sleep better, etc., all of which can lead to improved outcomes. Therefore, the control group does not actually represent the average patient.
Related to last week’s discussion about p-values, researchers and regulatory bodies want to make sure the active treatment (i.e., the actual treatment being tested) leads to a significant result; one way to do that is to compare the treatment group to a placebo group and see if differences between them are statistically significant. However, they also want to control for the placebo effect where they can in order to ensure that the control group represents the average patient as much as possible; this informs experimental design.
In a placebo-controlled trial, one group of participants receives the active treatment, while another group receives a placebo. Control groups in this type of study may still receive standard of care in addition to a placebo if the active treatment is, for example, an investigational drug in conjunction with standard of care.
There are different types of placebo-controlled studies. In a placebo-controlled, single-blind study, the participants are unaware of which treatment they are receiving, but the researchers know. For example, in a single-blind drug trial, participants may receive either the actual medication or a placebo pill. The participants do not know which treatment receiving, but the researchers do. This can diminish the placebo effect; however, when researchers know who is being given active treatment vs. placebo, it can cause them to unintentionally treat certain participants differently or expect certain results, which can impact the participants and affect the data. Generally, single-blind studies are not highly regarded since they are perceived to have an inherent bias. In contrast, in a placebo-controlled, double-blind study, neither the participants nor the researchers know who is receiving the treatment and who is receiving the placebo. This is why a placebo-controlled, double-blind design is often seen as the gold standard by regulatory bodies. With that said, this design may not be possible due to ethical and/or practical concerns. Other trial designs like active-controlled and crossover studies may include a placebo arm to provide additional evidence of a treatment’s safety and efficacy, while still controlling for the placebo effect.
Beyond its role in research and regulation, it is important for patient advocates to understand the placebo effect.
- First, it plays a role in informed decision making. If, for instance, clinical trial data in a particular disease area are demonstrating regular improvement in placebo arms, patient advocates may advise their patient community to consider already-accessible treatments or holistic approaches. Additionally, the regular improvement in placebo arms may represent better adherence to management plans or heathier lifestyle choices, in which case patient advocacy groups may consider ways to increase these in their patient community outside clinical settings.
- Second, patient advocacy groups may consider advocating for clinical trials that better account for the placebo effect, such as active-controlled and/or double-blind designs, and the inclusion of patient-reported outcomes measures.
- Finally, patient advocates ought to educate their patient community about the placebo effect to promote informed decision making.
