WHAT IS TO COME
In this first part of the book, we describe many reversals and estimate the frequency of medical reversal. We describe the harms of our broken system. Many are obvious, but there are some surprising harms of medical reversal. The repercussions may go further than you imagine. In part 2, we provide you with an understanding of evidence-based medicine, an understanding that will prepare you for the remainder of the book and allow you to question the next report about a “revolutionary new treatment.” Part 3 focuses on the causes of medical reversal. Money, of course, is involved, but in this case it is not the entire problem. The seeds of reversal are sown at the start of medical school and are nourished throughout the medical industry.
In part 4 we propose solutions for the problem of medical reversal. Our solutions are not a checklist and a vague call for you to be prepared when you see the doctor. We show just where changes can be made to medical education, medical research, and the process by which treatments are approved, so as to eliminate ineffective therapies. We also offer suggestions about how individuals can become better consumers of health care, how to be people who are unlikely to want, or be given, treatments that do not work. Because fundamentalism, in all its forms, is dangerous, we end by discussing those times when it is not necessary to demand that practices be based on ironclad data.
We hope that through reading this book you will understand the scope of the problem of medical reversal—how reversal affects every part of the doctor-patient relationship. This understanding may very well change your opinion of “feeling better.” It will certainly affect what you do when you feel well, in order to stay healthy, and what you do when you feel unwell.
2 SUBJECTIVE OUTCOMES :: WHY FEELING BETTER IS OFTEN MISLEADING
IN CHAPTER 1 WE DISCUSSED FIVE examples of reversal. Four of these—flecainide after heart attacks, stents placed in the coronary arteries of people with stable angina, atenolol as a treatment for hypertension, and mammograms for women in their forties—were similar in that they failed to improve what are considered objective end points. These are end points that we can easily measure: life events (death, heart attacks, or strokes), lab values, or other measurable variables (weight, blood pressure). The fifth reversal we discussed was quite different. Vertebroplasty was intended to improve a subjective end point. It was supposed to help people’s pain.
Doctors cringe every time a new study makes headlines announcing that the treatments we have been prescribing do not work. Patients feel even worse, often becoming confused, angry, and skeptical. These reports usually tell us that the treatment does not improve an objective end point: the blood-pressure pill that was supposed to reduce mortality really does not. It confounds everyone even more when a treatment that was meant to improve a subjective end point is reversed. When the study came out reporting that the vertebroplasty procedure did not work, a woman who had the procedure for a spinal compression fracture—an ailment that had been causing a great deal of distress right up until the procedure—might say, “What do they know? Let me tell you, it works.” The response of her doctor to these results would be similar. “I don’t care what the study says, I do this procedure and I know my patients feel better afterward.”
Disbelief is strongest when it comes to medical reversals that have to do with how people feel. When a reversal occurs because a treatment that was supposed to save lives (but had never been shown to) is proved ineffective, we cannot be very surprised. Sure, we thought it made sense mechanistically, but we never really had evidence of efficacy. When a treatment that was supposed to make people feel better, and did seem to make people feel better, is shown not to, that is devastating. Doctors assumed the intervention worked because their patients told them that it did. That seemed like evidence enough. This chapter presents multiple examples of these sorts of reversals.
In the era of evidence-based medicine, medical research has not given subjective end points the importance that they deserve. This is ironic, since most people go to the doctor to feel better. Doctors often pursue treatments that improve survival while making patients miserable in the process. Patients usually have precisely the opposite goals—they value feeling better much more than living longer. So when a new study suggests that the procedure that made you feel better actually had no effect—well, that is a pill that is hard to swallow.
THE CHALLENGE OF JOINT PAIN
As an example of how surprising one of these reversals can be, imagine this. You are 55 and have some knee pain that has been going on for about six months. It started out of the blue, is moderate in severity, and X-rays you had looking for osteoarthritis were pretty normal. With some rest and ibuprofen, your knee feels better, but the need to favor it during your regular activities is beginning to frustrate you. At a follow-up visit, your doctor suggests an MRI (magnetic resonance image) because he thinks your exam is consistent with a meniscal tear. The MRI shows a degenerative tear, one caused not by trauma but by wear on the knee. Your doctor suggests that you have surgery to repair this. He tells you the knee finding is abnormal, that it is easily repaired with a “relatively noninvasive surgery,” and that you will be better after the procedure. Hearing this, you eagerly agree. After an outpatient surgery followed by a home exercise regimen, you are feeling better. You think, “Boy, that was the right thing to do.”
Before discussing why this procedure, arthroscopic knee surgery to repair degenerative meniscal tears, is a wonderful example of a therapy that does not work—despite having been done for years to improve a subjective end point—let’s consider some background. The menisci are small pieces of cartilage, nicely described as crescents, that sit inside our knees. They allow the joint to move smoothly and disperse the forces that the knee must bear every time we take a step. The menisci sometimes tear. Tears can be traumatic (you have almost certainly heard of athletes missing whole seasons after meniscal tears) or degenerative. Degenerative tears are much more common. These tears sometimes occur as our knees age, and they are becoming increasingly common as our society grows older and heavier. Arthroscopic surgery is a minimally invasive orthopedic procedure in which the surgeon operates through scopes placed inside the joint through small incisions.
Arthroscopic surgery to repair degenerative tears of the menisci is big business. Each year in America, 700,000 patients undergo the procedure with the goal of relieving pain. The price tag for all these procedures is $4 billion a year. You would think that a procedure this common must work.
However, in 2013 two studies specifically examined arthroscopic knee surgery. The first found that surgery followed by physical therapy (as is always done) was no better than physical therapy alone. The study suggested that starting with a noninvasive approach would markedly decrease the need for surgery. The results of the second study was even more striking. This study found that surgery was no better than sham surgery. The researchers randomly assigned patients with degenerative meniscal tears and no osteoarthritis to sham surgery or to actual surgery. Patients randomized to the sham procedure went to the operating room. While there, the surgeon inserted the scopes, looked around in the knee, and generally pretended to do surgery. A patient who had sham surgery was in the operating room for the same amount of time as one who had real surgery. Both groups went on to have physical therapy. There were no differences in pain and functioning at 2, 6, or 12 months after the procedure.
So if arthroscopic surgery to repair degenerative meniscal tears does not work, why have patients and doctors sworn by it? When it comes to feeling better, we have known for years that procedures can elicit a placebo effect. What is the placebo effect? A placebo is any intervention that is not known to have, or intended to have, physiological benefits. A placebo might be a pharmacologically inert sugar pill or an ineffective intervention such as a sham surgery. When patients are given a placebo and have an improvement in their condition, beyond what is expected with a tincture of time, we call that the placebo effect.
The placebo effect is rea
l and has been supported in many studies. There have even been successful efforts to determine the underlying physiology of the effect. In a famous study in the 1970s, patients undergoing surgery for impacted molars received placebos for postoperative pain. When the patients whose pain responded to the placebo were given the drug naloxone, a drug that blocks the effect of morphine, the benefit of the placebo disappeared. This study, along with similar ones, strongly suggests that the placebo response is due to real physiological changes in the body. When we are experiencing pain, our brains secrete endorphins, which are natural substances similar to morphine. The placebo effect is, however, not universal. Attempts to define an average placebo effect, by analyzing the effect in many, varied studies, have been unable to determine one. That said, it does seem that the placebo effect is most common when it comes to therapies meant to reduce pain and that the effect tends to be relatively short-lived.
Because the placebo effect is strongest for subjective end points (nobody has ever proved that a placebo can make you live longer), we must make sure that studies of treatments meant to improve subjective end points are perfectly controlled. The participants in the control arm of a study (those people not getting the treatment) need to receive an intervention that is as close as possible to the real thing, so that both the treatment group and the placebo group attain an equivalent placebo effect. For instance, comparing surgery to exercise would not be a good study. After recovering from the surgery, you may feel better even if the surgery did not help. You will feel better because you expected to, you wanted to, and you were told by someone you trusted that you would. The appropriate study is comparing surgery to the most comparable thing—sham surgery.
THE ROLE OF SHAM SURGERY
If arthroscopic surgery to repair degenerative meniscal tears does not work, even though it seemed like it did, what about other orthopedic procedures? Consider those procedures that are so common we do not even imagine that they may not work? The anterior cruciate ligament (ACL) is one of the four ligaments that hold the knee together. It is commonly torn in sports (football, soccer, skiing) and is generally repaired without a second thought. We fix it because it is broken and because it seems to make people better. It has, however, never been rigorously tested—meaning it has never been tested in a randomized controlled trial with a sham-surgery arm. It turns out that the vast majority of orthopedic procedures for pain still have no sham-controlled studies. As a specialty, orthopedics has been reluctant to perform rigorous studies with sham-surgery controls.
Often the ethics of sham surgery is used as justification not to do these studies. Is it ethical to perform a sham procedure? Consider the converse question: is it ethical not to do a study with a sham-surgery control? When we institute a practice without this sort of evidence base, as we did with the meniscal surgery discussed earlier, we perform an operation half a million times a year, collecting billions of dollars, without any idea whether it even works. Estimating even a minimal complication rate of 0.1 percent for arthroscopic surgery (infection is an inevitable risk with any surgery), at least 500 people each year are suffering from a procedure that does not work.
Although it might seem extreme to question procedures that reasonably ought to work (and appear to work), the evidence supports skepticism. Reconstruction of torn ACLs might be the next procedure to be reversed, or at least to become less common. A study in 2010 randomized young, healthy people with recent ACL tears to early ACL repair with physical therapy (the current standard of care) or physical therapy followed by ACL repair only for those patients who did not get better. It turned out that with this approach, about half of the patients were able to avoid surgery. It will be interesting to see the results of the obvious follow-up study: patients with ACL tears all receive physical therapy, and those who do not get better are then randomized to ACL repair versus sham repair. The results might surprise us.*
SUBJECTIVE END POINTS OTHER THAN PAIN
Studies of vertebroplasty and arthroscopic surgery to repair degenerative meniscal tears demonstrate the power of sham procedures in untangling the complicated way our bodies experience pain. But what about other subjective end points? Is pain unique in its susceptibility to placebo response? Let us consider one of the most common ailments to affect healthy people: asthma. Nearly 300 million people worldwide carry a diagnosis of asthma. The treatment of asthma is a mainstay of any internist’s or pediatrician’s practice. During the throes of an asthma exacerbation, people become acutely aware of their breathing; they suffer with wheezing, chest tightness, and shortness of breath. People with asthma are quick to recognize the power of two puffs of the potent medicine albuterol. Delivered as an aerosol, albuterol dilates the airways, relieving the symptoms of asthma.
A study in the New England Journal of Medicine comparing asthma treatments is instructive when we consider treatments aimed at improving subjective end points—in this case shortness of breath. People in this study were randomized to four different therapies: an albuterol inhaler; a placebo inhaler; sham acupuncture; and no intervention. After use of the treatment, both objective and subjective end points were evaluated: spirometry, a test of how well air moves out of the lungs; and a questionnaire asking patients how they felt. The objective measure of lung function was no surprise: only albuterol improved how much air patients could move. The subjective outcome results, however, were a bit of a shock. Patients reported that all three therapies were better than doing nothing and all three were equally effective.
What this study shows is that even when considering how good you think your breathing is, the placebo response is robust. Those of us without lung problems rarely even know we are breathing. However, for people with asthma, breathing can take center stage. Asthmatics can often tell you whether their breathing is normal or “a little tight.” Even among these people, who are highly attuned to their own bodies, the placebo response can rival an active drug. This study encourages further caution toward interventions that claim to make us feel better.
The take-home lesson is that we have to be skeptical of even the practices that make us feel better. We need to test these interventions to make sure the effect is real—an effect of the treatment itself, not just the effect of being told that the treatment works. You might argue, “If people feel better, who cares if the response is a placebo response.” That argument is reasonable. In fact, every doctor-patient interaction benefits from the placebo effect. When we, as physicians, see patients and prescribe effective medications, our patients also benefit from the belief that the medications will help them. It is unlikely that a doctor has ever given you a medication and said, “This pill has been shown to work, but I doubt it will do anything for you.” This is not just true of practitioners of traditional, Western medicine; practitioners of complementary medicine may rely on the placebo effect to an even greater extent.
AN ACCEPTABLE PLACEBO?
There has been quite a bit of ethical debate over the years about using placebos. We think a few things limit their use as an acceptable medical practice. First, people see doctors to receive proven therapies, not treatments that might work. Going back to the days of patent medicines and snake oil is not something many of us would favor. Second, there may be real harm associated with prescribing treatments whose only effect is that of a placebo. If placebo interventions are expensive, potentially harmful, or delay or replace proven therapies, their use is clearly unethical. In today’s world, especially in the world of American health care, it is hard to imagine a placebo therapy, prescribed by a doctor, that is not expensive, does not carry some risk of harm, or does not replace a more effective, proven therapy.
Ted Kaptchuk, a professor at Harvard, is an expert in the placebo effect and has spent much of his career studying its nuances. One of his recent studies aims to convince even the most ardent skeptic how the placebo effect might be used appropriately. As we mentioned in chapter 1, one of the major quandaries regarding placebo therapies has to do with the use of deception. Dece
ption seems integral to achieving the placebo effect, and a modern cornerstone of medical ethics is that deceiving patients is never acceptable. Few of us wish to return to the days when doctors would fail to tell patients their cancer was terminal, or even that they had cancer.
Kaptchuk sought to test whether the placebo effect would still work even without deception. He decided to select an ailment about which there is widespread belief that psychological stressors played a role. He chose irritable bowel syndrome, or IBS.
IBS has a worldwide prevalence of 10 to 15 percent and is one of the top 10 reasons people go to the doctor. It is a gastrointestinal disorder characterized by abdominal discomfort, and, depending on the person, constipation or diarrhea or both. Little is known about the biological cause of the disease, but for years the observation was made that the placebo effect can lead to improvement in the condition. For this reason, Kaptchuk selected IBS as his laboratory.
In a study, 80 people with IBS were randomized to two groups. Half received no treatment, and the other half received a sugar pill and were told that the pill had “self-healing properties.” All other treatments for IBS (such as laxatives or antidiarrheal medications) were continued. Remarkably, people who received a sugar pill and were told that this was a pill made only of sugar had a statistically significant improvement in their IBS symptoms and felt better than those who did not. Kaptchuk proved that even without deception, the placebo effect could occur. As he put it, “Our results challenge ‘the conventional wisdom’ that placebo effects require ‘intentional ignorance.’”
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