The revenge of the son of the myth of "placebos without deception"

Back when advocates of “alternative” medicine were busily trying to legitimize their quackery by first renaming it “complementary and alternative medicine” (CAM), long before CAM “evolved” into “integrative medicine,” they really believed that if their favorite woo were to be studied scientifically it would be shown to be efficacious. Thus was born the Office of Alternative Medicine in the NIH, which later became the National Center for Complementary and Alternative Medicine (NCCAM), which more recently became the National Center for Complementary and Integrative Health (NCCIH), thus utterly purging itself of the word “alternative.” Both reflecting and influenced by NCCIH, over the last 25 years, increasingly academic medical centers have been feverishly studying quackery, often funded by NCCIH, and “integrating” it into real medicine. Thus was born the phenomenon of quackademic medicine, the infiltration of quackery into medical schools and academic medical centers.

There’s just one problem. As the actual double blind placebo-controlled randomized clinical trials (RCTs) of acupuncture, reiki, homeopathy, and various forms of the quackery advocates associated with NCCIH and investigators in bastions of quackademic medicine were done, it rapidly became very clear that these treatments produced effects indistinguishable from placebo controls; in other words, they didn’t work. Normally in medicine, when that happens the treatments that fail randomized clinical trials are abandoned. True, the process of abandoning such treatments is messier and longer than we might like to admit, but eventually they are abandoned.

When it comes to integrating quackery into medicine, however, because it was never science that motivated quackademics to begin with, when RCTs come up negative for acupuncture, homeopathy, reiki, or whatever, they cannot accept that their woo doesn’t work and simply walk away. So instead, for example, they make excuses. They do “pragmatic studies” without placebos, even though such studies are only appropriate after a treatment has been validated as efficacious in RCTs. Alternatively, they basically concede that their treatment doesn’t do anything better than placebo but then start arguing that they “work” by “harnessing the power of placebo” effects to “induce natural healing,” misrepresenting placebo effects as the power to use one’s mind to heal oneself. Never mind that this argument never flies with conventional science-based medicine and represents a flagrant double standard in which CAM is held to a much lower standard of evidence. Again, this is about belief, not evidence. Never mind that lying to patients to invoke placebo effects is the resurrection of medical paternalism.

The need for deception is, of course, a major problem with arguing that physicians should be able to use placebos, to tell them that a sugar pill is something effective. Ethically, this has always been a dubious thing for a doctor to do, but in the era of shared decision-making between doctors and their patients that has emerged from the paternalistic “doctor knows best” era of 50 or 60 years ago it’s even more problematic than before. To combat this narrative, there has emerged the narrative of “placebo without deception.” The foremost advocate of this narrative is our old buddy Ted Kaptchuk, who first promoted it in a big way six years ago with an open label study of placebo pills plus standard of care versus standard of care alone on irritable bowel syndrome. I discussed this study when it came out.

Unfortunately, Kaptchuk is back in the news saying virtually identical things:

Conventional medical wisdom has long held that placebo effects depend on patients' belief they are getting pharmacologically active medication. A paper published in the journal Pain is the first to demonstrate that patients who knowingly took a placebo in conjunction with traditional treatment for lower back pain saw more improvement than those given traditional treatment alone.

"These findings turn our understanding of the placebo effect on its head," said joint senior author Ted Kaptchuk, director of the Program for Placebo Studies and the Therapeutic Encounter at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School. "This new research demonstrates that the placebo effect is not necessarily elicited by patients' conscious expectation that they are getting an active medicine, as long thought. Taking a pill in the context of a patient-clinician relationship -- even if you know it's a placebo -- is a ritual that changes symptoms and probably activates regions of the brain that modulate symptoms."

I was half tempted to direct you to my discussion of Kaptchuk’s first “placebo without deception” study and leave it at that because this study suffers from virtually the same flaw as the last one, but that’s not what you come to this blog here. You come here because you like your Insolence Insolent and verbose detailed.

One thing I’ve learned when evaluating these studies is that you really, really have to look long and hard at the methodology, because when you do you will almost always find that there is deception involved. For example, like this new trial, Kaptchuk designed his IBS trial so that the patients knew they were getting placebos, even going so far as to label the pill bottles “Placebo.” Back then, then he and his team observed a difference in reported symptoms between those taking the placebo pills plus usual care compared to those with usual care and proclaimed that they had successfully invoked placebo effects without deception. There was just one problem, and it was in the script doctors used when discussing placebo effects with patients:

Patients who gave informed consent and fulfilled the inclusion and exclusion criteria were randomized into two groups: 1) placebo pill twice daily or 2) no-treatment. Before randomization and during the screening, the placebo pills were truthfully described as inert or inactive pills, like sugar pills, without any medication in it. Additionally, patients were told that “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.”

And the study was advertised thusly:

Participants were recruited from advertisements for “a novel mind-body management study of IBS” in newspapers and fliers and from referrals from healthcare professionals. During the telephone screening, potential enrollees were told that participants would receive “either placebo (inert) pills, which were like sugar pills which had been shown to have self-healing properties” or no-treatment.

So basically, right off the bat the investigators recruited patients who were interested in “mind-body” effects and then told them that placebo effects could produce powerful “mind-body self-healing processes” in rigorous clinical testing. There was the deception, because even the most generous and sympathetic characterization of the rigorous research existing on placebo effects would not justify such a description. As I said at the time, not only did Kaptchuk et al deceive their subjects to trigger placebo effects, whether they realized or would admit that that’s what they did or not, but they might very well have specifically attracted patients more prone to believing that the power of “mind-body” interactions. Yes, patients were informed that they were receiving a placebo, but that knowledge was tainted by what the investigators told them about what the placebo pills could do.

So what about this study? This time around Kaptchuk is not the first author; Cláudia Carvalho is. He’s also not the senior listed author. Irving Kirsch is. Be that as it may, this study has Kaptchuk’s fingerprints all over it. Entitled Open-label placebo treatment in chronic low back pain: a randomized controlled trial, it is basically that. The verbiage is very similar:

Administrating fake pills to harness placebo effects poses an ethical conundrum for physicians in clinical practice due to the widespread belief that deception is necessary for placebo pills to work (eg, pretending sugar pills are drugs or, more commonly, giving genuine medications that have no known effect on the condition).²⁹ However, 4 studies have directly tested the effect of an open-label placebo (OLP) prescription, and all indicated that patients reported benefits after taking pills presented honestly as placebos. Three were small pilot studies.^19,25,28 The fourth was a controlled trial in irritable bowel syndromeand showed significant, clinically meaningful benefits over no-treatment controls.¹⁷

The received wisdom is that clinical administration of a placebo requires deception (or double-blind conditions) to be effective. How is it that a placebo treatment is able to produce effects even when the participants know that the pill is inert?

This is the spin. Even though that controlled trial did indeed invoke deception to promote placebo effects by greatly exaggerating what placebo effects were, Carvahlo et al blithely ignore that and simply declare the study to be strong evidence that one can invoke placebo effects without deception. They even move on to assume that the point has been demonstrated and ask how such a thing could be true? Then they go on to do the same thing that Kaptchuk did six years ago.

From the methods section:

Participants were recruited from advertisements for “a novel mind–body clinical study of chronic low back pain” in flyers, posters, Facebook posts, magazine advertising, and referrals from health care professionals.

And:

After informed consent, all participants were asked if they had heard of the “placebo effect” and explained in an approximately 15-minute a priori script, adopted from an earlier OLP study,¹⁸ the following “4 discussion points”: (1) the placebo effect can be powerful, (2) the body automatically can respond to taking placebo pills like Pavlov dogs who salivated when they heard a bell, (3) a positive attitude can be helpful but is not necessary, and (4) taking the pills faithfully for the 21 days is critical. All participants were also shown a video clip (1 minute 25 seconds) of a television news report, in which participants in an OLP trial of irritable bowel syndrome were interviewed (excerpted from: http://www.nbcnews.com/video/nightly-news/40787382#40787382).

So basically, they used the same talking points from the previous study, plus clips of happy study participants to prime the patients that placebo effects can be “powerful.” Again, people that patients tend to believe, doctors and nurses and other health care professionals, telling them that sugar pills coule invoke powerful healing effects. In other words, this study is just like the IBS study, only with back pain.

Its design was fairly simple. There were two groups: open label placebo (OLP) + treatment as usual (TAU) versus TAU. Participants were eligible if they were over 18 years old and had persistent back pain for more than three months’ duration. Exclusion criteria included usage of opioid pain medications within the prior 6 months or if they had a history of refusing to take oral medication. Other exclusion criteria included pain due to cancer, fratures, infections, prior back surgery, disk degeneration due to trauma or aging, conditions that make treatment difficult (e.g., paralysis or psychosis), and other conditions thought to interfere with interpretation, such as fibromyalgia, rheumatoid arthritis, etc. Then there were the pretty standard exclusions: pregnancy, breastfeeding, surgery within the last 30 days, and the like. So basically what investigators were left with were patients with chronic low back pain, almost certainly musculoskeletal in nature, and no major anatomic abnormalities from trauma, prior surgery, or cancer who had not taken opioids in the last six months. In other words, this is mild chronic back pain, a condition that’s very likely to be prone to placebo effects, which is likely why this group was chosen. Overall, 97 subjects were randomized, and ultimately there were 42 subjects in the TAU group, 41 in the TAU + OLP group. There were three dropouts in the TAU group and 4 in the TAU + OLP group, leaving 38 in each group, but an intent-to-treat analysis was used, so that all 83 of the original participants were analyzed. Outcomes were measured at baseline and after 11 and 21 days using questionnaires measuring total pain score and the Roland–Morris Disability Questionnaire.

One thing that bothered me looking at Table I. (The paper is open access; so you can look for yourself if you’re curious.) There are no statistics. By the “eyeball” test, the two groups look pretty comparable in all the baseline characteristics measured, but I like to see statistics. I’m funny that way. Be that as it may, the results of this study were utterly predictable, given its design:

Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P , 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (20.3 to 0.8) in the TAU group. Openlabel placebo treatment also reduced disability compared to TAU (P , 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (21.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5).

And:

A reduction in pain of 27.9% has been found to correspond to clinical ratings of “much improved” and a 30% reduction has been recommended as an indication clinical significance.7,9 There was a clinically significant 30% reduction in both usual and maximum pain in the placebo group compared to reductions of 9% and 16% in usual and maximum pain, respectively, in the continued usual treatment group. Open-label placebo reduced minimum pain by 16% compared to an increase in pain of 25% with TAU. There was also a 29% reduction in pain-related disability in placebo group compared to 0.02% in the TAU arm.

So, basically, both groups improved, but the OLP group improved more, just as one would expect from placebo effects. Yet, none of this stopped Carvalho et al from concluding:

Our data suggest that harnessing placebo effects without deception is possible in the context of a plausible rationale. More research on this possibility is warranted in cLBP and other conditions defined by self-appraisal.

As is frequently the case when investigators are interviewed by the press, no doubt excited about their results, they went beyond these claims in a non-peer-reviewed source. You saw Kaptchuk regurgitate pretty much the same nonsense he did six years ago with the IBS study. To that, he added more, and Carvalho chimed in:

"It's the benefit of being immersed in treatment: interacting with a physician or nurse, taking pills, all the rituals and symbols of our healthcare system," Kaptchuk said. "The body responds to that."

"Our findings demonstrate the placebo effect can be elicited without deception," said lead author, Claudia Carvalho, PhD, of ISPA. "Patients were interested in what would happen and enjoyed this novel approach to their pain. They felt empowered." Kaptchuk speculates that other conditions with symptoms and complaints that are based on self-observation (like other kinds of pain, fatigue, depression, common digestive or urinary symptoms) may also be modulated by open-label treatment.

"You're never going to shrink a tumor or unclog an artery with placebo intervention," he said. "It's not a cure-all, but it makes people feel better, for sure. Our lab is saying you can't throw the placebo into the trash can. It has clinical meaning, it's statically significant, and it relieves patients. It's essential to what medicine means."

"Taking placebo pills to relieve symptoms without a warm and empathic relationship with a health-care provider relationship probably would not work," noted Carvalho.

One more time: No, Mr. Kaptchuk and Dr. Carvalho. Your results do not show that the placebo effect can be elicited without deception. They do not. You can keep saying that, keep spinning your results that way, but the exact same problem applies to this study as to the IBS study in 2010. You had to hype up what placebo effects were and tell participants, without justification, that they produced “powerful” mind-body effects, priming them with advertisements touting the same thing. The “placebo without deception” narrative was not supported by evidence in 2010, and this new study doesn’t support the narrative either.

Finally, we already know that interacting with a kind physician or nurse makes people think they feel better. That’s something that can be done honestly, without deception. Using placebos can’t.