December 21, 2017
By Greg Peters
The words placebo and sham rarely come up when a doctor and patient sit down to talk about surgeries like having an appendectomy or a heart valve repaired.
Many people are, however, very familiar with the use of placebos as part of randomized clinical trials for drug testing. In these trials, participants agree to be part of a controlled experiment where a portion of the group receives the actual medication being studied, while the rest of the group gets a placebo, or sugar pill. These trials are set up so neither the doctor nor the patient knows who is getting the real medication. This blind testing is done to ensure that the drugs are truly working as intended and to discount any placebo effects.
In the new book "Technological Changes in Modern Surgery: Historical Perspectives on Innovation," co-edited with Thomas Schlich, Christopher Crenner, M.D., Ph.D., Robert Hudson and Ralph Major Professor of the History and Philosophy of Medicine and chair of the Department of History and Philosophy of Medicine at the University of Kansas Medical Center, outlines how the origins of using placebo surgeries as tools in randomized clinical trials can be traced to KU Medical Center in the late 1950s. In the chapter "Placebos and the Progress of Surgery," Crenner describes how two identical random clinical trials performed independently thousands of miles apart used placebo surgeries to shed light on the success of a then-widely accepted surgical procedure.
Placebo surgeries, while much less prevalent today than clinical drug trials, follow a similar premise. Patients sign up for randomized clinical trials not knowing whether they are getting the real treatment or a placebo. To lay people and critics alike, exposing a patient to the perils of surgery might seem ethically questionable, however, over the years, the use of placebo surgeries have proven to be an integral part of establishing the credibility of surgical procedures. Without these placebo surgeries, it is impossible to exclude the influence of what is typically a strong desire by surgeon and patient alike to have the surgery succeed, Crenner said.
Randomized clinical testing, especially in the area of pharmaceuticals, really took off in the years following World War II thanks in large part to the efforts of academic physicians seeking accurate, unbiased results. The problems of bias in non-randomized and uncontrolled drug trials were well documented, so the timing was right for change to come to medicine.
At KU Medical Center in 1958, E. Grey Dimond, M.D., and his colleagues had doubts about the validity of ligation of the internal mammary arteries as a treatment for cardiac angina. In a typical case, the surgeon would open the chest of an anesthetized patient and tie off the two arteries as they emerged into the superficial muscles of the chest wall. This was done to redirect blood to the patient's ailing heart.
Working in conjunction with Dimond, Fred Kittle, M.D., followed the ligation procedure in an operating room at Bell Memorial Hospital, making a shallow incision in the chest of a patient, who had consented to be part of a clinical trial. To keep pre-surgical bias to a minimum, even the operating room team did not know until the last minute which procedure they would be performing on the patient. In this case, however, instead of tying off the arteries, Kittle left them alone, sutured the patient shut, and sent him to recovery.
At the same time the team at KU Medical Center was putting the internal mammary artery ligation surgery to the test, another group at the University of Washington, led by a young medical researcher named Leonard Cobb, was conducting an identical clinical trial. Both groups reported similar results.
"I talked with Dr. Dimond about this trial before his death a couple of years ago, and he remembered in detail how remarkable it was to see the men returning after the fake procedure reporting improvement in their ability to walk without chest pain," Crenner said.
In those days long before the internet connected the world instantaneously, the two groups knew nothing about each other's work even though both were funded by the National Heart Institute, which is now part of the National Institutes of Health (NIH). Remarkably, Dimond and Cobb first learned about each other when they were both booked to present the reports of the parallel studies at the annual meeting of the American Heart Association. The results of both studies showed that the widely popular internal mammary artery ligation had the same results as placebo surgery, giving further credence to the use of randomized clinical testing.
"This made it clear to all observers that the results were solid," Crenner said. "People were pushing hard to demonstrate the replicability of clinical trials, and here they had it immediately."
The use of placebo surgeries as part of randomized clinical testing continues to have critics on many levels. In addition to exposing patients to infections and unnecessary anesthesia, Crenner points out in his book that critics would say these placebo surgeries demonstrate a willingness to put the desire for sound knowledge of therapeutic effects above our care for the safety and interests of individual patients.
While the popularity of placebo surgeries as a testing methodology has risen and waned over the years, they continue to play a role in randomized clinical trials. Recently, a study published in "The Lancet" and reported this month in the "New York Times" suggested that heart stents - long a staple in relieving chest pain in thousands of patients each year - may, in fact, be useless for many of the patients.
For the study, a cardiologist at Imperial College London, looked at 200 participants with chest pain severe enough to limit physical activity and profound coronary artery blockage. All were treated for six weeks with drugs to reduce the risk of a heart attack before the real or fake insertion of a stent. Both groups received drugs post-surgery to prevent blood clotting.
Six weeks later, both groups reported less chest pain and performed better on treadmill tests. Current medical guidelines in this country say stenting is appropriate for patients with blocked arteries and chest pain, but those guidelines were based on studies that did not account for the strength of placebo effects in patients who have a serious invasive procedure done.
"Placebo surgeries are uncommon and controversial at least around the boundaries," Crenner said. "But, in my mind, they are perhaps poised to increase significantly, especially in countries with closed, centrally funded health systems where there is a desire to decrease the use of expensive surgeries that are potentially non-therapeutic."
At KU Medical Center, great care is taken to make sure participants enrolled in clinical trials understand all the factors involved. Because a certain amount of risk is involved in any surgery, the decision to perform any procedure is taken with the utmost caution and care by health care professionals involved in research at KU Medical Center.
"We always ensure participants in clinical research trials are completely informed of the risks and options, whether the trials involve surgery or medication" said Richard J. Barohn, M.D., vice chancellor for research at KU Medical Center. "Unlike studies where placebo surgeries are involved, in many of our trials here at KU Medical Center, we are comparing surgical outcomes to those achieved using medications; or we may be comparing different surgical interventions.
"Regardless of the trial," Barohn continued, "they are always done with the full consent of participants, and we are diligent about their safety."
While clinical trials involving placebo surgeries certainly aren't the norm, as Crenner noted in his book, KU Medical Center has earned a place in medical history. Crenner credits much of the inspiration for the book to a symposium honoring Dr. Marc Asher's support for documenting the history of spinal surgery at KU Medical Center and nationally. Published in 2017 by the University of Rochester Press, the book uses case studies to explore the technological changes that have come about in surgery during the past 200 years. The book investigates how surgical practices have been shaped by not only technical innovations but by changes in society as well.