4 Common Rater Concerns During Placebo Response Mitigation Training... and How to Address Them

In clinical drug development, researchers face the challenge of proving that a drug works—by proving that it works better than a placebo. The magnitude of placebo response, where participants (and their caregivers in relevant cases) experience and report real improvement from physiologically inactive treatment, can dramatically influence the outcomes of a study. In some cases, potentially causing an effective drug to look like it has no efficacy at all. 

This concern prompts many study teams to offer training directed at mitigating placebo response. The following is a review of how clinical site staff—especially raters—respond to placebo response migration training – including their common concerns and questions. 

What Is the Placebo Response? 

True placebo response is the phenomenon where a participant’s condition improves after receiving a treatment that contains no active drug. In clinical drug trials, this “treatment” is the placebo, given to the control group to compare against the experimental, active drug. 

The tricky part? The placebo effect is real. People can and do get better because of their expectations, belief in the treatment, or simply from the care and attention they receive from raters and site staff during the trial.  

Participants can also experience change in a clinical trial due to regression to the mean or spontaneous factors (such as getting a new job or experiencing a sudden illness), but these are out of the researcher’s control.  

For a deeper understanding of placebo response and mitigation methodologies, visit this blog →

Why Placebo Response Can Be a Problem

The more the placebo group improves, the greater the chance it will mask the beneficial effects of the study drug. Even drugs with proven efficacy might not show a statistically significant benefit if the placebo group does too well. 

In fact, research shows that placebo response has increased over the past few decades, especially in areas like depression and pain (e.g., Kemp et al. 2008, Walsh et al., 2012). In some modern trials, placebo groups have actually outperformed the results of active medications tested years earlier (add references). 

What Influences the Placebo Response?

The placebo effect is shaped by several human factors:

• The participant’s expectations and beliefs
• The quality of the rater-participant relationship
• Rater and site staff’s expectations and beliefs
• Caregiver expectations and beliefs
• The tone and behavior of site staff

That’s why it’s important for everyone at the trial site who interacts with participants to be trained in placebo response mitigation strategies. This training helps reduce unintentional cues that might enhance the placebo effect and skew results. 

Common Concerns from Raters—and How to Address Them 

Clinical raters often agree that trying to guess which group the participant is in should be avoided and that participants (and their caregivers) should be dissuaded from guessing as well.  

However, during placebo response mitigation training sessions, raters have raised concerns about changing their usual communication/patient interaction style as well as confusion about how the placebo response can compromise a study.  

Here are some of the most frequent concerns that can arise during training—and how to reframe them. 

🔹 Concern 1: "Shouldn’t we be instilling hope? That’s what we do in clinical care." 

Response: Instilling hope is a cornerstone of clinical treatment. But in a clinical trial, we are conducting research, not delivering usual clinical care. The purpose is to observe and measure the true effect of the drug—not to make participants feel better through interpersonal warmth or reassurance. Raters should understand that their role in a study is different from their role in clinical practice.  

In a clinical trial, we can’t predict what is going to happen, so neither the rater nor the participant can count on improvement regardless of whether they get the active drug or a placebo. 

In addition, we harness placebo response in clinical practice because we are prescribing treatments that have already been demonstrated as effective and therefore, we can rely on the expectation of improvement to enhance treatment response.  

🔹 Concern 2: "Shouldn’t we be encouraging a placebo response to help boost the effectiveness of the drug?” “If the drug works and the placebo response increase positive outcomes, isn’t it better to combine them?” “Doesn’t a placebo response in both the active group and control group cancel each other out?”

Response: It’s a common misconception that boosting placebo effect in both the control and experimental groups cancels each other out. In reality, it’s the difference between the two groups that reflects the drug’s actual effect. Augmented placebo response should add equally to the response rate in both groups, but since there tends to be a ceiling effect limiting the total response rate higher placebo response rates tend to narrow the difference between placebo and investigational product. 

So, if the placebo response is too strong, the gap between the placebo’s effect and an active drug’s effect can look weak.

🔹 Concern 3: "If we act less warm, won’t that hurt the participant—or the study?"

Response: Mitigating placebo response does not mean being cold or rude. Instead, it means striking a neutral, professional tone. Think of it as “busy yet efficient.” Raters are collecting data, as accurately as possible, not providing treatment. Scripts and site-specific protocols can help raters find a style that feels authentic while still protecting the integrity of the study.

🔹 Concern 4: "What if this participant is also my patient in clinical practice?"

Response: This can be challenging. If a participant knows the rater from a clinical, therapeutic setting, they may expect the same level of empathy or informal conversation. That’s where role induction comes in. 

Role induction is the process of explaining to the participant:

• What their role is in the study
• What behaviors are expected
• What the rater’s role is—and isn’t
• What kinds of interactions will and won’t happen

Doing this early (ideally at screening) sets clear boundaries and helps participants adjust to the different tone of a research visit versus an appointment where treatment as usual is delivered. 

Final Thoughts: Placebo Mitigation Is About Balance 

Managing placebo response is a delicate balance. In training raters on placebo response mitigation, we are not trying to eliminate human connection—the rater is trying to standardize and remain neutral enough to see the drug’s actual effects. 

With proper training, clinical raters can shift from a therapeutic mindset to a research-oriented one—without losing professionalism or respect for participants. And with effective placebo response mitigation, clinical trials can more accurately determine whether a treatment really works.