Can the Placebo Effect Have Real Clinical Value?

Some cases suggest that simply believing that we’re getting better has healing effects.

The following is an excerpt from Cure: A Journey Into the Science of the Mind Over Body, by Jo Marchant.

Bonnie Anderson didn’t notice the water on her kitchen floor until it was too late. One summer evening in 2005, the 75-year-old had fallen asleep on her Davenport sofa while watching TV. She doesn’t remember what program was on, a decorating show, maybe, or an old movie (she doesn’t like the bad-language ones, or the bloody kind). When she woke it was dark, and she walked barefoot into the kitchen for a glass of water, without bothering to switch on the lights. But the water purifier had been leaking and she slipped on the wet tiles, landing flat on her back.

Unable to move, Bonnie felt an excruciating pain in her spine. “It was scary,” she says. “I thought, ‘My God, I broke my back.’” Her partner, Don, dragged her down the hall and put a blanket over her, and a couple of hours later she was able to get up onto the sofa. Thankfully she wasn’t paralyzed, but she had fractured her spine—an injury common in elderly people whose bones have been weakened by osteoporosis.

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Bonnie lives with Don in a small, white bungalow in Austin, Minnesota. She worked for 40 years as a telephone operator for the town’s main employer, Hormel Foods (makers of Spam), and has stayed active into her retirement. She has orange makeup, big white hair and a busy social life, and loves nothing more than an 18-hole round of golf, a sport she has played all her life. But the accident left her devastated. She was in constant pain and couldn’t even stand up to do the dishes. “I couldn’t sleep at night,” she says. “I couldn’t play the golf I wanted to play. I’d go and sit in the den with a heating pad.”

A few months later, Bonnie took part in a trial of a promising surgical procedure called vertebroplasty, which injects medical cement into the fractured bone to strengthen it. Don drove Bonnie to the hospital—the Mayo Clinic in Rochester, Minnesota—just before dawn on a cold October morning. She walked out of the hospital after the procedure, and felt better immediately. “It was wonderful,” she says. “It really took care of the pain. I was able to go back to my golfing, and everything I wanted to do.”

Almost a decade on, Bonnie is still delighted with the outcome. “It was a miracle how well it turned out,” she says. Although breathing problems are now starting to slow her down, she isn’t limited by her back. “I have a birthday coming up, I’ll be 84,” she chuckles. “But I still plan on playing a little golf this summer.”

The vertebroplasty apparently healed the effects of Bonnie’s fractured spine. Except there’s something Bonnie didn’t know when she took part in that trial: she wasn’t in the vertebroplasty group. The surgery she received was fake.

In 2005, when Bonnie slipped on her wet floor, the technique of vertebroplasty was rapidly gaining popularity. “Orthopedic surgeons were doing it. Physiatrists [rehabilitation physicians] were doing it, anesthesiologists were doing it,” says Jerry Jarvik, a radiologist from the University of Washington in Seattle. “Anecdotally there were lots and lots of reports as to how effective this procedure was. You’d get them on the procedure table, inject the cement, and they’d effectively jump off cured.”

Bonnie’s surgeon at the Mayo Clinic, David Kallmes, says he too had seen “positive” results from the procedure, with around 80 percent of his patients getting substantial benefit from it. But nonetheless he was starting to have doubts. The amount of cement that surgeons injected didn’t seem to matter much. And Kallmes knew of several cases in which cement was accidentally injected into the wrong part of the spine, and yet the patients still improved. “There were clues that maybe there was a lot more going on than just the cement,” he says.

To find out what, Kallmes teamed up with Jarvik to do something groundbreaking—at least in the field of surgery. They planned to test the effectiveness of vertebroplasty against a group of patients who would unknowingly receive a pretend operation. Although such placebo-controlled trials are routinely used to test new drugs like secretin, they are not generally required for new surgical procedures, partly because it often isn’t seen as ethical to give patients fake surgery. Kallmes points out, however, that with surgery just as with drugs, untested therapies risk harming millions of patients. “There’s nothing unethical about a sham trial or a placebo trial,” he says. “What is unethical is not doing the trial.”

Kallmes and Jarvik enrolled 131 patients with spinal fractures, including Bonnie, at 11 different medical centers worldwide. Half of them received vertebroplasty and half received a fake procedure. The patients knew that they only had a 50 percent chance of receiving the cement, but Kallmes went to great lengths to make sure that the sham surgery was as realistic as possible, so that the trial participants wouldn’t guess which group they were in. Each patient was taken into the operating room, and a short-acting local anesthetic was injected into his or her spine. Only then did the surgeon open an envelope to discover whether the patient would receive the real vertebroplasty or not. Either way, the operating team acted out the same predetermined script, saying the same words, opening a tube of the cement so that its characteristic smell of nail polish remover filled the room, and pressing on the patient’s back to simulate the placement of the vertebroplasty needles. The only difference was whether or not the surgeon actually injected the cement.

Afterwards, all of the patients were followed for a month, and asked to rate their pain and disability using questionnaires. The study was published in 2009. And even though Kallmes had harbored some doubts about the procedure, he was shocked by the results. Despite all of the apparent benefits of vertebroplasty, there was no significant difference between it and the fake operation.

“Perhaps the doctors and patients in all of these cases really were fooled by a combination of random chance and wishful thinking.”

Both groups substantially improved, however. On average, their pain scores were reduced by almost half, from 7/10 to just 4/10. The disability score was based on a series of questions such as: can you walk a block, or climb stairs without holding a handrail? At the beginning of the trial, the patients answered no to an average of 17 out of 23 questions, a score that is categorized as “severe disability.” A month after the surgery, they scored on average just 11. Although some were still in pain after the procedure, others, like Bonnie, were practically cured. A second trial of vertebroplasty carried out in Australia was published around the same time, with very similar results.

The patients’ improvement was probably due to range of factors. Pain symptoms can fluctuate, and vertebral fractures do heal, slowly, over time. But both Kallmes and Jarvik believe that to produce such a dramatic improvement, there must have been something else going on—something in the patients’ minds. Just as with secretin, it appears that the mere belief they had received a potent treatment was enough to ease—and in some cases banish—their symptoms.

The phenomenon in which people seem to recover after they are given a fake treatment is called the placebo effect, and it is well-known in medicine. Clinical trials consistently show a strong placebo effect across a wide range of conditions, from asthma, high blood pressure and gut disorders to morning sickness and erectile dysfunction. In general, however, scientists and doctors view it as a mirage or trick: a statistical anomaly where people would have improved whether they received the treatment or not, combined with a morally dubious phenomenon in which desperate or gullible people are fooled into thinking they are better when they really aren’t.

Back in 1954, an article in the medical journal The Lancet stated that placebos comfort the ego of “unintelligent or inadequate patients.” Although doctors might not put it so bluntly today, attitudes haven’t changed much since then. The placebo-controlled trials introduced at around that time have been one of the most important developments in medicine, allowing us to determine scientifically which medicines work and which don’t, saving countless lives in the process. They form the bedrock of modern medical practice, and rightly so. But within this framework, the placebo effect is of no interest beyond being something to guard against in clinical trials. If a promising therapy is shown to be no better than placebo, it is thrown out.

Trial results show that neither secretin nor vertebroplasty has any active effect. So according to the rules of evidence-based medicine, the improvements experienced by patients like Parker and Bonnie are worthless.

Cure: A Journey Into the Science of the Mind Over Body


Yet when Sandler told the parents in his study of secretin that he had found no benefit for the hormone over placebo, a huge 69 percent of them still wanted it for their kids. Likewise radiologists have refused to give up on vertebroplasty. After Kallmes and Jarvik’s report was published, the pair were attacked in hostile editorials and personal letters, and even screamed at in a meeting. “People felt extraordinarily strongly that we were taking away something that was helping their patients,” says Jarvik. In the U.S., many insurers still cover the procedure, and even Kallmes still carries out vertebroplasties regardless of his trial results, arguing that for many of his patients there is no other option. “I see patients get better,” he says. “So I still do the procedure. You just do what you need to do.”

We see similar cases again and again. In 2012, a popular class of sleeping pills called Z-drugs was shown to be of little value after accounting for the placebo effect. The same year, the sedative ketamine was tested in a double-blind trial for cancer pain; previous studies had described its effects as “complete,” “dramatic” and “excellent,” yet it too proved to be no better than placebo. In 2014, experts analyzed 53 placebo-controlled trials of promising surgical procedures for conditions from angina to arthritic knees, and found that for half of them, sham surgery was just as good.

Perhaps the doctors and patients in all of these cases really were fooled by a combination of random chance and wishful thinking. But by continuing to dismiss the experiences of so many people, I can’t help wondering if we are also throwing out something that could be of real help. So here’s my question. Might the placebo effect, instead of being an illusion that we should puncture, sometimes be of real clinical value—and if it is, can we harness it without exposing patients to potentially risky treatments?

Or to put it another way, can a simple belief—that we are about to get better—have the power to heal?

Adapted from Cure: A Journey Into the Science of the Mind Over Body Copyright © 2016 by Jo Marchant. Published by Crown Publishers, an imprint of Penguin Random House LLC, on January 19, 2016.

Meet the Writer

About Jo Marchant

Jo Marchant is a science journalist and author of Cure: A Journey Into the Science of Mind Over Body (Crown, 2016). She’s based in London, England.