I was delighted to find an article on the ethics of “open-label” placebo use in the pediatric population in the August issue of Pediatrics, particularly one partially penned by Arthur Caplan and Perri Klass. The primary author, however, appears to be Brit Trogen, a medical anthropologist currently studying medicine at NYU School of Medicine with an accomplished background in science journalism. Sadly I was more than a bit disappointed in their discussion of the subject, as it revealed a poor understanding of placebo, making the common mistake of confusing what we see in clinical trials with real world practice. But it wasn’t all bad.

The concept of placebo comes up frequently in discussions of both science-based medical practice and the seemingly infinite array of pseudomedical approaches to healthcare we write about here on SBM, and there is certainly some room for disagreement between reasonable people. Trogen, Caplan, and Klass make this clear, and they accurately point out some of the potential pitfalls of incorporating “open-label” placebo into pediatric treatment protocols. But they give placebo effects too much credit in my opinion, and rely too heavily on studies performed by Ted Kaptchuk, who frequently proselytizes the existence of “placebo without deception” based on studies that use deception.

I’ll run through the main points made by the authors since most readers will be unable to access the full article.

They start with a general description of what a classic placebo response is:

Placebos (sham treatments such as sugar pills or saline injections) are thought to elicit improvements in clinical outcomes by mimicking medical therapies, thereby improving patients’ expectations of getting better

This is overly simplistic.

Later in the article they add a bit more nuance:

The term “placebo effect” is often used colloquially to describe a small, confounding, or insignificant response. In both child and adult populations, however, placebos can reduce the frequency and severity of disease symptoms in patients at a level on par with many pharmacologically active drugs.

And this is extremely misleading.

Placebo in the context of a clinical trial is a combination of many factors, such as regression to the mean and the natural course of subjective complaints, and largely an artifact of the way we run clinical trials and measure outcomes. Patients in the placebo arm of a trial may appear to have symptom reduction on par with the treatment group, but it’s mostly an illusion. Patient expectation likely plays a very small role and, when it is compared to patients in a “no treatment” group, often doesn’t amount to much at all. In fact, the longstanding belief in the existence of a significant true placebo effect in clinical trials is based on some highly dubious research.

Placebo in clinical trials doesn’t result in the improvement of objective outcomes. Patients may subjectively believe that their pain, which is where there is the most potential for actual clinically meaningful benefit, is improved but they won’t have much in the way of improved function. I’m not saying that there might not be a role for improved patient perception in certain circumstances, but this can be achieved without sacrificing patient autonomy or parent authority.

The authors even mention this fact:

While the placebo effect plays a role in virtually every clinical intervention, the use of placebos as stand-alone treatments within medicine has largely been discouraged due to concerns about patient deception.

A deception that is unethical in my opinion. Unfortunately they follow this statement with the increasingly common narrative of the “placebo without deception”, or “open-label” placebo. They claim that these “concerns have been addressed” by research over the past decade, research primarily belonging to Harvard’s Ted Kaptchuk, who is trotted out whenever NPR or some other news organization wants a comment on how magical placebo can be. They describe “open-label” placebo as a “powerful new methodology” that involves full transparency and patient awareness, in the same breath as they admit that patients are lied to:

Patients also are told, however, that such placebos have been found to produce benefits in individuals with their condition, preserving positive patient expectations.

They claim that “open-label” placebo has been determined to be consistent with the ethical principles of informed consent and patient autonomy. This determination was made by, you guessed it, Ted Kaptchuk. So the man whose focus in life appears to be the justification of incorporating placebo into clinical practice agrees with himself.

I found the following claim very interesting:

Although studies of open-label placebos in pediatrics are scarce, reviews and meta-analyses generally find that children have higher placebo-response rates than adults, suggesting pediatric populations may benefit at least as much, and perhaps more, from attempts to implement placebo treatments into clinical practice.

I would have assumed that this would be the case. Remember that these responses are seen only in subjective outcomes. It makes sense to me that there would be higher risk of study artifacts resulting in the perception of improvement in kids, who are also more amenable to improvement with distraction/TLC. And there might be added artifact because of the necessity of parental assessment of outcomes. And higher placebo response in clinical trials does not automatically mean that they would have clinically meaningful responses outside of the context of a trial.

Remember that this is supposed to be an unbiased assessment of the ethics of “open-label” placebo in pediatric care when you read the following statement:

Based on these considerations, the a priori prohibition of placebos from clinical practice may deprive patients of a potentially effective mode of treatment, while simultaneously exposing them to the heightened side effects, uncertain efficacy, and higher financial costs associated with pharmacologically active medications.

This bold claim, and some blatant fearmongering about prescribing drugs “off-label” in children, is supported by a pilot study on “open-label” placebo in children with ADHD. The results weren’t impressive and it only involved 26 kids and a 2 week observation period. I don’t think it’s fair to make any causal claims, especially regarding ethical considerations, even if the parents in the study were big fans of placebo. I don’t think they would have signed their child up for the trial if they weren’t.

Now the good parts.

When it comes to potential problems with the use of “open-label” placebo, the authors do much better. After claiming that the “functional mechanism” of placebo is poorly understood and a rather silly mention of possible “nocebo effects” that is. I agree with them, however, when they raise the concern that increased use of placebo, deceptive or not, might add to the common belief that all complaints require a medical or pharmaceutical treatment of some kind. We might condition even more parents to seek medical care for minor pediatric complaints that are self-limited and benign.

They also raise the concern that widespread use of “open-label” placebo might interfere with the establishment of trusting relationships between patients and their medical providers, particularly if done in a haphazard fashion. It might be interpreted by some as an implication that the complaint is all in the patient or parent’s head. It may seem as if the doctor is giving up.

They absolutely nail the final potential problem with this approach, so much so that I’ll just quote the entire paragraph because I couldn’t put it better myself:

More concerning is the possibility that placebo use could lead patients to develop false or misguided beliefs either about the placebo compound itself or the concept of “mind-body healing” overall. It is possible that patients and/or parents could equate the benefits they receive from placebos with a legitimization of other forms of so-called alternative medicines, or develop the inaccurate belief that “positive thinking” is sufficient to cure all manner of serious illnesses, forgoing proven treatments. Similarly, on learning of the benefits of placebos from their physician (or, just as likely, from the Internet or by word of mouth), individuals could feasibly attempt to “self-prescribe” inert substances to themselves or their children to lessen their use of other medications. Particularly in situations in which drug dosages must be maintained above critical levels over time, such as for antiseizure or hypothyroid medications, independent and unsupervised attempts to cut back or eliminate drug dosages could pose a serious health risk.

Other than the whole, “lying to patients is unethical” issue, that right there is my biggest fear. Practitioners of various forms of irregular medicine who truly believe in their own implausible nonsense have denied that their treatments rely on the various placebo effects historically. But as scientific evidence has time and time again proven their magical thinking wrong, many proponents have shifted focus over to placebo. In particular, many so-called integrative medicine providers working in academic settings, as well as folks like Ted Kaptchuk, not only want us to believe in placebo, they need us to believe in placebo without deception.

Conclusion: A mixture of good and bad

Trogan, Caplan, and Klass don’t appear to have a good grasp of the concept of placebo effects, but they ultimately do not endorse the widespread implementation of “open-label” placebo in pediatric medical practice. They do suggest a “possible limited role” instead, and one that is “closely monitored.” And, naturally, more research to better sort this out. In my opinion, the available research does not support claims that placebo has clinically meaningful benefits outside of what can be achieved through good science-based care, or that “placebo without deception” even exists.

Posted by Clay Jones

Clay Jones, M.D. is a pediatrician practicing at Newton-Wellesley Hospital in Newton, MA, and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @skepticpedi and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey.