Note: I just got back from TAM; so if you happened to see a different version of this post somewhere else, now you know why.
Last week while I was at TAM, a study appeared in the New England Journal of Medicine (NEJM). It is another beautiful example of how proponents of complementary and alternative medicine (CAM) are able to spin even hugely negative results into something that supports CAM. Because I was at TAM, I didn’t actually notice the article at first, but notice it I did eventually. Upon seeing it, my first question was: What on earth are the editors of NEJM smoking. Oddly enough, that reaction wasn’t provoked because I thought the study itself was horrible. Nor was air sickness due to turbulence the reason I felt as though I had to ask the flight attendant on my flight home to get me a barf bag. Rather, it was an acute sense of nausea brought on by the spin applied to this particular study to try to persuade the reader that it is evidence of powerful placebo effects in The study under question was performed at Harvard, with Michael E. Wechsler as its first author and Ted Kaptchuk as its senior author. It actually wasn’t all that long ago that I blogged about another Kaptchuk study, in particular claiming in a truly Humpty Dumpty moment that it is possible to have placebo effects without deceiving the patient.
If only placebos could produce potent anti-emetic responses in me. Alas, they can’t.
The current study is entitled, Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma. Personally, I like this title. It’s a fine title, as it tells the reader in essence what the trial design is in only a few words. And it’s actually a reasonably good study, a solid randomized clinical trial. Of course, it’s not so much the trial design that goes disastrously awry. Rather, it’s the interpretation of the results of the RCT that devolves into propaganda for quackademic medicine in which subjective improvement is used to argue that placebo medicine is good, even when no objective improvement is observed in a disease, even when we have good drugs that produce objective improvements as well as subjective improvements.
This study basically compared four different interventions:
- Treatment with Albuterol
- Sham acupuncture using the classic retractable needle (note that this was only single-blinded)
- Placebo inhaler
- No treatment at all
Inclusion criteria were as follows:
- Men and women age>or= 18 with a diagnosis of asthma
- Meet American Thoracic Society diagnostic criteria for
- asthma
- Currently using a stable asthma regimen (no med. changes for 4 weeks)
- Ability to withhold short-acting bronchodilators for 6 hours prior to each visit (see Spirometry description)
- Ability to withhold long-acting bronchodilators for 48 hours prior to each visit (see Spirometry description)
- Presence of reversible airflow obstruction as demonstrated by an improvement in FEV1 of at least 12 % following the inhalation of a β-agonist after 10 am. at screening visit.
Exclusion criteria were straightforward:
- Lung disease other than asthma
- Respiratory tract infection within the last month
- Active tobacco use
- Asthma exacerbation requiring the use of systemic
- corticosteroids within the past 6 weeks
- Prior experience with acupuncture
These criterial guaranteed that the patients selected have only mild to moderate asthma. Of course, it would be highly unethical to take people with severe asthma off of their bronchodilators; so medical ethics pretty much prevents testing placebos on people with more severe disease. Still, I can’t help but wonder whether the results reported would have been different in more severe asthma and if the subjective improvement would have been nearly as great. In any case, this study ended up including 39 patients, after 79 were screened, 46 underwent randomization, and 7 dropped out during the protocol. Patients who completed the protocol underwent the following procedure:
These patients returned within a week and were assigned to a randomly ordered series of four interventions — active albuterol inhaler, placebo inhaler, sham acupuncture, or no-intervention control — administered on four separate occasions, 3 to 7 days apart (block 1) (Figure 2). This procedure was repeated in two more blocks of four visits each (blocks 2 and 3), during which the interventions were again randomly ordered and administered. Thus, each subject received a total of 12 interventions. Albuterol and the placebo inhaler were administered in a double-blind fashion and sham acupuncture in a single-blind fashion, and the no-intervention control was not blinded. As before, short-acting and long-acting bronchodilator therapy was withheld for 8 hours and 24 hours, respectively, before each intervention. The no-intervention control condition differs from the natural history of asthma, since it controls for nonspecific factors such as attention from study staff, responses to repeated spirometry, regression to the mean, natural physiological variation, and any effects arising from the hospital setting. Nonetheless, no-intervention controls are the best approximation of no treatment in an experimental design. The study was conducted in accordance with the protocol (available at NEJM.org).
Now for the punchline. Everyone’s heard the old cliche that a picture is worth a thousand words, and this is exactly the sort of situation where that’s true. So, without further ado, for your edification, here a graph of the objective results of this study, namely the FEV1 for the four groups:
(Click to embiggen)
Not surprisingly, a known, effective bronchodilator had a very strong effect on the actual, objectively measured lung function of these patients. However, it should be noted that all groups improved, even the no-treatment group; it just improved much less than the albuterol group, and the sham acupuncture and placebo albuterol groups were indistinguishable from the no-treatment arm. In fact, in the supplemental data, there is also a table showing that in 32 of the patients exhaled nitric oxide (FENO) was measured, with identical results. Immediately after treatment, FENO increased in patients treated with double-blind albuterol by 5.9%, in contrast to patients treated with placebo inhaler, placebo acupuncture, and no treatment, all of whom demonstrated no significant change in FENO. This graph is about as clear and compelling evidence as there can be within the limits of a relatively small trial, that placebo responses do not change the underlying physiology of the disease of asthma or produce any objectively measurable improvements in lung function the way that real medicine does.
Now, for your edification and comparison, here is a graph of the self-reported subjective improvements.
(Click to embiggen.)
The results are pretty striking, aren’t they? They were so striking that I thought about doing an animated gif that flips back and forth between these two graphs in order to drive home the point to the audience. The albuterol, sham acupuncture, and placebo albuterol groups all demonstrated a significant improvement in symptoms, while the no-intervention control did not. However, here’s an important point. The scale used was a visual analog scale from 0 to 10 in which 0 means no improvement and 10 means complete resolution. So, again, even though the albuterol, sham acupuncture, and placebo albuterol groups all demonstrated subjective improvement, so did the no-treatment control arm, just less. In other words, all groups reported improvement, even those who received no treatment.
There’s another graph buried in the back of the supplemental data that I now wish we had also shown. Basically, it’s a look at how many patients responded objectively to treatment, as defined by an improvement in FEV1 of 12% or more, at each of the three sessions they did. The results and pattern are striking
(Click to embiggen.)
Notice that, as expected, the vast majority of the patients responded at each session to the albuterol (3/3 sessions). In contrast, only 3% of patients responded 3/3 times to placebo, sham acupuncture, or no treatment. In fact, what’s striking is how similar the three graphs look and how different they look from the graph of patient responses to albuterol. Again, the message is very clear: Real medicine produces real, objectively measurable changes in physiology towards a more normally functioning state. Placebo medicine does not. In any rational, science-based discussion, this would be the end of the story. Placebos don’t work in asthma.
But that’s not the message that was being spread about this story, and here’s where the NEJM, less than a year after its massive fail in publishing a credulous Michael Berman acupuncture article and a clever bait-and-switch article looking at Tai Chi in fibromyalgia, allowed quackademic language to try to make left right, up down, and a negative result an indication that placebo medicine is a good thing.
As I read the discussion of this paper, I could almost hear the cracking of bones as Kaptchuk went into major contortions to try to explain his negative result. Even though nowhere did the authors really explicitly state their real hypothesis, the design of the study made it painfully clear to anyone who understands clinical research that their hypothesis going in was that placebo responses would result in changes in objectively measured lung function in asthma. They were sorely disappointed, and the contortions of language that went into the discussion were plain to see. The authors implied that it might have been their use of a new, not really validated, patient-reported measure of asthma improvement. Or maybe, they argue, FEV1 isn’t a good measure of the severity of constriction of the airways in asthma, even though spirometry has been a reliable, well-validated test for asthma severity for decades. This is especially true in an academic medical center with a lot of pulmonary specialists. While spirometry can be unreliable in primary care settings and other settings where there isn’t a lot of experience performing it, such a description does not apply to Harvard-affiliated hospitals. At least I would hope not.
Overall, the spin on this study is not that placeboes don’t result in objectively measurable improvements, which is the correct conclusion. Rather, the spin is that subjective symptoms are as important or more important than objective measures; so let’s use placeboes. In the paper itself, Kaptchuk doesn’t quite say that. He first makes a perfectly reasonable point that, if subjective and objective findings don’t correlate, go with the objective findings. Then he does some handwaving:
Indeed, although improvement in objective measures of lung function would be expected to correlate with subjective measures, our study suggests that in clinical trials, reliance solely on subjective outcomes may be inherently unreliable, since they may be significantly influenced by placebo effects. However, even though objective physiological measures (e.g., FEV1) are important, other outcomes such as emergency room visits and quality-of-life metrics may be more clinically relevant to patients and physicians.
My jaw dropped when I read this. “Other outcomes” besides objective measures of disease severity may be “more clinically relevant”? The spin goes way beyond that, though. I have to think that the reviewers kept the authors from getting too frisky with their desire to advocate placebo medicine and promote subjective outcomes as being more important than objective outcomes. No such restraint seemed to inhibit the author of the accompanying editorial, Daniel E. Moerman, Ph.D., who, alas, appears to be based practically in my back yard at the University of Michigan-Dearborn. I had never heard of him before; so I did what all bloggers do when they encounter an unknown. I Googled him. His CV is here, and this is what I found:
Daniel E. Moerman is the William E. Stirton Professor of Anthropology at the University of Michigan — Dearborn, so recognized for his distinguished scholarship, teaching, and professional accomplishments. Because of his work in the field of Native American ethnobotany, Professor Moerman often receives calls from the American Indian community, such as an inquiry from the Menominee in Wisconsin, asking him what kinds of plants they should include in the restoration of their indigenous ecosystem. He acknowledges that we are deeply indebted “to those predecessors of ours on the North American continent who, through glacial cold in a world populated by mammoths and saber-toothed tigers, seriously, deliberately, and thoughtfully studied the flora of a new world, learned its secrets, and encouraged the next generations to study closer and to learn more. Their diligence and energy, their insight and creativity, these are the marks of true scientists, dedicated to gaining meaningful and useful knowledge from a complex and confusing world.”
He’s also known for having written a book entitled Medicine, Meaning and the “Placebo Effect,” part of which can be found here, in particular this doozy of a quote:
There is much objection among physicians to the very existence of something called the placebo effect. It often seems to bother doctors enormously that the fact of receiving medical treatment (rather than the content of medical treatment) can initiate a healing process. Why? I think it is because medicine is rich in a particular kind of science. Medical education is filled with science. In the US, all students must score high on the “Medical College Admission Test” in order to be admitted to medical school. Students are allowed a total of 345 minutes to complete the exam. Eight five minutes are devoted to “verbal reasoning,” and 60 minutes to “writing sample.” The remaining 200 minutes (585%) are split evenly between “physical sciences” and “biological sciences.” It is apparently important that physicians understand levers, inclined planes, the acceleration of falling bodies, the life cycle of insects, and the process of photosynthesis. The kind of science that doctors have to learn is the simpler sort of science, the mechanical kind. Physicists worked out the mechanics of simple machines (levers, planes) in the seventeenth century. In our times, they have been working on much slipperier subjects: quarks, chaos, the “weak force,” and the oddest of quantum phenomena. Cause and effect are far less easy to detect in these matters than in the study of falling bodies…But it is the latter, not the former, in which physicians are schooled. And there is very little social science in medical education where one must address the complexities and subtleties of, say, emotion, or ritual, or culture.
If you detect shades of Deepak Chopra in there, you are correct. Moerman invokes quarks, quantum theory, and other complexities and contrasts it to the “simpler” sciences that physicians apparently learn. One can almost feel the contempt for us poor, deluded physicians. Perhaps if I had known a bit about Professor Moerman, my jaw ouldn’t have dropped so far when I read this in the editorial accompanying the NEJM study:
What do we learn from this study? The authors conclude that the patient reports were “unreliable,” since they reported improvement when there was none — that is, the subjective experiences were simply wrong because they ignored the objective facts as measured by FEV1. But is this the right interpretation? It is the subjective symptoms that brought these patients to medical care in the first place. They came because they were wheezing and felt suffocated, not because they had a reduced FEV1. The fact that they felt improved even when their FEV1 had not increased begs the question, What is the more important outcome in medicine: the objective or the subjective, the doctor’s or the patient’s perception? This distinction is important, since it should direct us as to when patient-centered versus doctor-directed care should take place.
He then goes on to write:
For subjective and functional conditions — for example, migraine, schizophrenia, back pain, depression, asthma, post-traumatic stress disorder, neurologic disorders such as Parkinson’s disease, inflammatory bowel disease and many other autoimmune disorders, any condition defined by symptoms, and anything idiopathic — a patient-centered approach requires that patient-preferred outcomes trump the judgment of the physician. Under these conditions, inert pills can be as useful as “real” ones; two inert pills can work better than one; colorful inert pills can work better than plain ones; and injections can work better than pills.
I find it hard not to notice that Moerman has cast a very wide net; virtually any condition outside of trauma could fit into his definition. I can’t help but think that, if I, for instance, had asthma and the severity of my symptoms didn’t correlate well with my objectively measured lung function as estimated by FEV1, then I would want my lung function tuned up. And if I didn’t want my lung function to be improved, I would hope that my doctor would be able to educate me as to why it is important to make my lungs function better, even though I feel OK. Moerman would seem to advocate telling me, “Oh, no, Orac, don’t worry about those blue lips you have. That’s just an ‘objective’ finding. You feel OK, and, since symptoms are the most important thing and the reason that you come to a doctor in the first place, your feeling good is all that matters.” Yes, I realize that a Plexiglass box of multicolored blinking lights can’t have blue lips, its being a computer and all, but just go with me here on this one.
I’ll give you another example. Consider an epidural hematoma. If you crack your head hard enough, it can sheer or damage one of the epidural arteries. The typical clinical course is that the patient will be knocked unconscious due to head trauma. Later, he will regain consciousness and experience what is known in the biz as a “lucid interval” that can last several hours. What’s happening during that “lucid interval” is that the blood is still accumulating, but the hematoma hasn’t reached a large enough size yet to cause damage, but when it does the patient deteriorates rapidly. Frequently, one of those “objective findings” is a CT scan that shows a little epidural hematoma, which may or may not blossom into a life threatening epidural hematoma that can squash the brain against the inside of the skull. That’s an “objective” finding. Even though the patient feels well; that hematoma could expand and kill him in a few hours.
No doubt Professor Moerman or Ted Kaptchuk would claim that these are ridiculous and unfair examples. No doubt they would say that this is not what they’re talking about, and that’s probably true. I’ll even concede that the example of the epidural hematoma example was a bit over the top, but that was intentional.
However, whether they realize it or not, by elevating the subjective beyond the objective, and then offering placebo medicine for the subjective, these are exactly the sort of arguments they are making, when you strip them to their essence. No doubt Moerman or Kaptchuk would like to think that they would never, ever use such an approach for diseases with such potentially bad outcomes, but where do they draw the line? When, exactly, do we decide that subjective improvement is more important than objective improvement and by what criteria? Moerman makes a great show of saying, “First, do no harm,” but he seems to assume that not intervening in the abnormal physiology of some diseases doesn’t do harm. He’s wrong. It most definitely has the potential to do some harm.
Let’s return to asthma, since that is the disease that this study examined. Even if a person with asthma seems to feel fine with a lowered FEV1, there is a price to be paid for leaving asthma untreated, which, let’s face it, is what placebo medicine is, leaving the functional disorder untreated. For instance, there is evidence that early treatment after the diagnosis is made can prevent the airway remodeling that occurs in chronic asthma, in which airway constriction and inflammation lead to further narrowing of the airway and further functional decline. Moreover, if a case of asthma’s severe enough, a patient could be walking on the proverbial tightrope, where all it would take is a small insult to push him over into a life-threatening asthma exacerbation or pneumonia, whereas if lung function in an asthmatic is tuned up as well as it can be, I’ll have a lot farther to deteriorate to reach that dangerous point. Let’s also not forget: Asthma can and does kill, some 250,000 deaths per year worldwide. Choosing alternative medicine over effective asthma treatment because placebo responses lead to feeling better without altering the underlying illness, could very well lead to preventable asthma deaths.
In the end, I’m a bit torn about this study. On the one hand, it irritates me to no end how it is being sold to the public as evidence of “powerful” placebo effects and as evidence that we physicians should be doing more placebo medicine. On the other hand, the fact that CAM advocates are reduced to spinning studies like this the way they are is pretty darned conclusive evidence that they now know that, from the standpoint of therapy, the vast majority of CAM modalities do nothing and are in fact placebo medicine. The problem is, in some diseases, such as asthma, placebos run the risk of allowing serious harm from lack of effective intervention that actually alters the course of disease. If the therapeutic relationship is so damaged in the U.S. that the beneficial effects of provider-patient interactions are not being realized, whether you want to refer to these effects at the “placebo response” or something else, the answer is to fix medicine to make it easier and more rewarding for physicians to spend that time with patients. The answer is not to embrace magical thinking like that behind acupuncture, homeopathy, and huge swaths of CAM.
78 replies on “Dangerous placebo medicine for asthma”
So they took a bounch of mild to moderate asthmatics and gave them albuteral or placebo when they weren’t experiencing subjective distress, and then asked if they felt better? I have more severe asthma (I would not have qualified for that study) and when I am taking albuteral as a preventative (say, during a sinus infection) I can’t tell a major difference just by how I feel. I have to look at a peak flow. The only time I can tell is when I am in significant distress.
If your bronchial tubes are open enough that you can breathe normally and have decent O2 sat, opening them up more isn’t going to make you feel very different.
Or there’s this interpretation:
Placebos make you feel better.
Albuterol makes you feel better and actually makes you better.
Pick a recommendation.
If it’s a choice of placebo, acupuncture, sham acupuncture or albuterol, I’ll take the real treatment.
“Well, it does no harm” is all well and good, except for the fact that It does no good either.
Moerman would seem to advocate telling me, “Oh, no, [Orac], don’t worry about those blue lips you have.
Well, that’s what it should say. You’ve forgotten to remove your real name.
“colorful inert pills can work better than plain ones; and injections can work better than pills.”
What happened to ‘first do no harm’? Injections, because the patient might be stupid enough to think ‘oh, its in a injection, that’ll work’? Why not electric shock treatment then? That’ll clear you’re asthma up. I think Moerman has revealed the ‘working principle’ of ethnobotanical “medicine” here, have a witch doctor put on a mask, dance around, stress the patient, and they’ll “feel” better.
As far as “patient-centered medicine”, I think if you showed an asthmatic the first and second graphs here and said ‘which treatment do you want’, they’ll go for the medicine. But the authors of the article and editorial seem to think that /they/ are the ones who know better than the patient. They don’t want to replace ‘the privilege of western medicine with the patient’, they want to replace it with /themselves/.
NO! WRONG! The last thing you’d want to do is fool the patient into thinking they are getting better because of how they “feel” rather than objective results. By this logic, using a placebo to make them “feel” would result in LESS seeking of medical attention and possible overlooking of serious issues. *Facedesk*
I think one thing that makes the results of this study significant are that it brings into question the prevailing medical model that focuses on treating the body alone, while the problem of mind is either excluded or dismissed. As the results of this study point out, mind is an important aspect of the healing process and has the power to increase well-being on its own. This is what I take away from Kaptchuk’s study.
Did I read correctly that subjects were re-randomized for each of the 3 (four visit) sessions? Does this mean some folks got treatment in the following order: fake, real, fake?
If so, I would really like to compare the responses for each session in that group–after getting real medicine, did they still say the fake stuff helped?
Of course, even if they were fooled, it doesn’t change the fact that fake medicine gives fake results. In fact, until today, I was under the impression that “placebo effect” meant objective improvement from fake treatment, not merely subjective reports of improvement. Heck, if the placebo effect is just about duping the patient, then I see no ethical reason to even study it!
I saw this last week and knew it was begging for a blog. The results were interesting (for 39-person trial). I find it amazing that you can fool asthmatics into thinking there was an improvement, even though the majority of acute placebo treatments had no effect on their asthma. It’s amazing that the brain can be fooled into what it wants to believe instead of relying on actual body feedback. This study also stresses the importance of gathering quantitative data to assess asthma control: clearly, self-reporting is highly unreliable. Although, I suppose we already knew that.
@ 6 – I’m fairly certain you’re a Poe, but I think this study effectively proved that the mind is incapable of tricking the body into being well. It is remarkably good, however, at tricking itself into think it’s better.
Am I missing something or is their Figure 4 using a scale from 0 to 100% improvement, while both the caption and the text speak of a 0 to 10 points on a visual-analogue scale?
I mean, sure, it’s just a factor, and everybody understands how it’s meant, but had I been a reviewer I’d have asked them to make their figures and their descriptions match.
Hi Jake, What about the objective results? If you had asthma, would you rather ‘think you feel better’, or ‘think you feel better AND have an improved ability to breath’?
What was the point of the sham acupuncture? I really don’t see why they used it in this study. Surely sham acupuncture is only useful if you are comparing it with real acupuncture. In this study the placebo inhaler was the appropriate placebo to use. Something doesn’t seem quite right in this.
@DLC, but it does do harm, though.
If you leave asthma untreated, the inflammation in the airways gets worse, which makes them more ‘twitchy’ (asthma patient slang, means irritable and prone to bronchospasm) and swollen. More swollen means you have a harder time breathing at your baseline. More twitchy means that you become even more likely to have your aiways spasm. So you start having more attacks. Each attack further increases your inflammation, making it even more likely you’ll have another one.
Sooner or later, you might have an attack so bad that you can’t breathe at all. You turn blue, pass out, and die.
I’ve been to the point of turning blue and passing out before, when I was a kid. I was status asthmaticus, maybe minutes away from dead if it weren’t for doctors treating me properly. Because my parents (either out of ignorance, financial pressure, or the very wrong belief that it was all in my head or some combination of the three, I don’t know and don’t particularly care) didn’t treat my asthma properly until I was eight, I experienced that condition about twice a year for the first seven years of my life.
I can say with some authority that it’s not a nice way to go. You’re being smothered by your own body. Air gets trapped in your lungs, so your lungs swell, distorting your chest into a barrel chest (a very uncomfortable condition called air-trapping). Your breathing muscles are past the point of burning from exhaustion and each breath is acutely painful. When you cough (and you can’t not cough, it’s an instinctual attempt to clear the obstruction from your airways), it feels like someone’s stabbing you in the ribs. You might cough hard enough to throw up, piss yourself, pull muscles, or bruise or break ribs (I’ve done all of the above in attacks before). You will cough hard enough to burst blood vessels in your eyes. Your lungs fill with mucus, so now you’re drowning as well as smothering. Anyone trying to hug you or comfort you (and they will be trying to, if for no other reason than to make themselves feel like they’re doing something) in any physical way only increases the feeling of suffocation. You panic and struggle to breathe. You can’t not panic in this situation. Anyone who says otherwise is lying. The fact is, if you’re having an attack this bad, you’re dying and that’s what it feels like. People around you will also be panicking (unless they’re trained professionals, at least one person in a group seeing someone dying before their eyes is gonna panic) and yelling at you to remain calm, which will only make you more upset and make you panic more. Unfortunately, the struggle and coughing only irritates your airways even more and further worsens the attack. It is terrifying and painful and prolonged.
Even if you ignore the danger from it, there’s the issue of lost productivity: If you’ve ever had bronchitis, that’s how an uncontrolled asthma patient feels on a good day. If you’re feeling that rotten, it’s hard to concentrate or get anything done. You’ll probably make stupid mistakes because you’re too tired because you were up five or six times last night and every night before that as long as you can remember. You’ll be cranky, irritable, and unpleasent to be around. If you work in a dangerous field, your lack of alertness will make you a danger to yourself and to those around you. Because you can’t breathe well, you’re slow, can’t keep up with anyone, and don’t tolerate exercise well. You probably need frequent breaks to catch your breath when doing anything at all physical, likely leading to people thinking you’re lazy and negatively affecting your job advancement and performance. If you’re a kid, it negatively affects your grades and how the other kids see you, so you get bullied.
Treating asthma with placebo is dangerous and has an overall negative effect on the health and quality-of-life of the patient. Though I’m not a doctor, I would say as an asthma patient who’s experienced the alternative, in an age where safe, effective treatments exist, refusing to treat asthma properly is doing harm.
To pile inaccuracy on inaccuracy, ABC News reported “Placebo Effect Rivals Steroid Benefit for Asthmatics”. Apparently, somebody at ABC had heard that steroids were used in asthma, and didn’t bother to check whether albuterol is a steroid. The study didn’t even look at steroids, which wouldn’t stop an acute asthma attack anyway; they are used for their long-term anti-inflammatory benefit.
Spin aside, it seemed like a nice study, although the news reporting failed to mention what I thought was the most striking finding: in terms of the objective measure of FEV, there was no placebo effect at all as compared to no treatment. The other thing not mentioned is that it is well known that subjective feelings are not a reliable index of lung function in asthma, so people with asthma often use a home FEV device to determine when they need intervention. Moreover, people can die from asthma attacks, so what the study actually strongly suggests is that a placebo could potentially be deadly, obscuring awareness of the warning signs of a severe asthma attack without actually improving function.
I wish they’d looked at blood oxygenation as well. It would probably follow FEV, but it would be nice to see that confirmed.
Okay, here’s what offends me about the idea of giving sham treatments in lieu of albuterol just because it improves subjective measures, even if there is no improvement to objective measures…..
Salmeterol.
Salmeterol is a drug similar to albuterol; it’s a beta-agonist that acts as a bronchodialator. Like albuterol, it does not actually treat the underlying inflammation. (This is why asthmatics are advised to see their doctor if they need to use their albuterol too often; albuterol taken quickly can relieve the problem before you get into the downward spiral of inflammation, but if it doesn’t, you need to do something about that inflammation. Usually, that means steroids.) But there is a difference; salmeterol is long-acting (albuterol wears off fairly quickly), and it doesn’t have the unpleasant side effects of albuterol. It is very good at relieving symptoms — so good, and so comfortable, that patients may take it daily and be unable to tell whether their asthma is actually improving. This has been pinned in the scientific literature as the reason why salmeterol-alone* therapy has a higher death rate than albuterol-alone, and actually a higher death rate than nothing whatsoever. The patients sometimes neglect their asthma attack until it is too late to help them, because they feel fine.
Now, I would think patients would give up on acupuncture much more quickly than they’d give up on salmeterol, but I could see people fooling themselves long enough to get into serious trouble. My grandmother, who has severe asthma, has always had a tendency not to take her symptoms seriously. On one occasion, she actually drove herself in to work, where her colleagues quickly realized she wasn’t at all well (she could barely talk, and definitely should not have been driving). She still refused to see a doctor, so they took the liberty of calling 911. The paramedics checked her out and then immediately put her on an albuterol nebulizer and rushed her to the hospital. It was over a month before she was well enough to return to teaching. So my grandmother was able to ignore her symptoms almost to the point of collapse without even pinning her hopes on a sham treatment; half the problem is that being unable to breathe leaves you hypoxic, which impairs judgement.
* It is not recommended to take salmeterol alone, but you can still get it as long as you take it with a steroid. Advair, for instance, pairs salmeterol with a steroid. It works, but the spooky part is that you can’t really tell when you’re better. Also, it’s ridiculously expensive.
As a layman, it makes me uneasy that journals such as the NEJM would so blatantly, by means of such things as Moerman’s editorial, suggest that whether a patient feels better is more important than whether the patient actually is better.
I’ve got a comment in moderation (don’t know what tripped the filter) but I find this very disturbing. The data’s pretty much unambiguous that the shams did nothing for objective measures of asthma, and I’m completely unsurprised at the subjective ones looking good. It is very hard to tell how bad one’s own asthma is. You pretty much have to carry a peak flow meter and use it regularly.
Jake: thinking you feel better is good, but actually *being* better is preferred, in my opinion. These scientists basically found that it’s easy to trick an asthmatic into thinking they’re better. That’s actually kind of scary to me, an actual asthmatic. I want my doctor to make me feel better by making me actually better. Also, did you notice that though acupuncture did as well as sham inhaler on the subjective measures, albuterol was still superior? That seems like a win-win to me. Make the patient feel better, and actually *be* better!
@DLC Except that in this case, as Orac points out, it does active harm by potentially delaying the point at which someone seeks treatment for a serious illness. I see this all the time and I’m not even a bleedin’ medic.
Placebos for frigging schizophrenia… Where can I find this idiot to punch him in the mouth? I wonder if he’ll follow his own deductions if ever he develops rhumatoid arthritis?
Patient-preferred outcomes. If a patient walks into a surgery and says “I want to die”, should that be a priority over trying to relieve what’s causing such extreme distress? If it was I wouldn’t be alive today, even if I still believe assisted dying should be an option for the terminally ill.
As an asthma sufferer I find it hard to believe anyone could not notice the difference between albuterol and a placebo in a true emergency situation. There might be a placebo effect during the calm setting of a scheduled office visit, but having once mixed up inhalers in an emergency (puff of steroid instead of albuterol) the lack of instant effect is rather noticeable.
Thank you, Orac : I had been feeling morose (” And there ain’t no cure for the summertime blues”) but this study changes that! I feel better now!
I’m somewhat surprised that they didn’t throw in Freud’s “Psychological reality is the only reality”- if they ran with that, they could toss figure 3 entirely. The use of self-report is fabled in alt med studies and is also their primary mode of advertisement,the testimonial: this should tell us something. Solid data based in objective measures isn’t as popular, I wonder why?
Woo-ful theoreticans blithly at work( @ AoA and other places) speak about their own observations of their children’s ups and downs and then postulate a treatment. Here’s what I think is really going on: the child’s ( activity level, aggressiveness,or lack of communication, etc .) varies stochastically ( or is multi-causal- internal and external- and difficult to dis-entangle) however, the parent-observer attributes the negative changes to a single external cause ( or perhaps 2 or 3) ( e.g. gluten, caseine, toxins) which is/ are then eliminated. Now random improvements are interpretted as being caused by the “treatment”. Works like magic because it is.
This reminds me of the “superstitious” pigeons: they’re fed on a random schedule, however they learn to repeat whatever they were doing when the food hatch opened. Some subjects turn in circles while others peck at a particular spot or bob their heads. These superstitious actions increase because they pigeons have, wrongly, learned to associate them with producing desired results. With which they have no connection except in the minds of the subjects.
If you peer into Mr Null’s justly famous health support group “studies” you’ll find that the dependent variables ( and there are lots)rely on self-reports. People who do a lot of work on changing their lifestyle radically are motivated to see improvement. Studies are actually collections of multiple testimonials. More superstitious pigeons as well.
Alt med appears to subsist on self-report because it is most manipulable by external prompts. Expect to see change and you might, especially if the coaxing is in the form of finely-tuned advertising copy ( a/k/a natural health information sources) created and tested over many sales campaigns. Here’s where the only *real* science comes in : they study what sells.
The authors of the asthma study seem content at producing “feelings” of improvement and view this as being helpful in serious illness -such as schizophrenia, neglecting physiology! In which case isn’t the *physiology* of dopamine ( and othe neurotransmitters) responsible for the disordered feelings and symptoms in the first place? Physiology has a way of making itself known despite your feelings about it.
Mu — it appears they specifically were studying in patients with mild asthma. Personally, I tend to notice the side-effects of albuterol before I notice the improvement in my lung function, but this is partly because I have a natural tremor which is seriously aggravated by albuterol. It’s quite unpleasant. (But not being able to breathe is worse.)
There used to be this ad running on TV by the American Lung Association to educate people about the seriousness of asthma. It probably pissed off PETA to no end, but it depicted a goldfish taken out of water, its gill-covers opening as wide as they could and its mouth gaping with each “breath” as it struggled to keep oxygenated. Then, it was returned to the water. The point was that this is how asthma feels like. It feels like you are suffocating. Mostly because you actually are.
But that’s a severe attack. Milder attacks don’t feel so disturbing. They’re unpleasant, but you don’t feel like you’re dying. And it’s much easier to blow off the symptoms at that stage. (No pun intended.) After my grandmother nearly died because *she* didn’t realize she was having an attack, I no longer doubt the ability of people to ignore their own symptoms.
As a nurse and mother of two children who have asthma I can tell you that they have no perception of how well they are breathing at any given moment. They invariably think they are breathing just fine when in fact their peak flow is rapidly declining. It isn’t until they are audibly wheezing that they will report that they maybe having a problem.
Mu – I also have asthma, and when I take albuterol (fortunately I only have to take it rarely because my asthma isn’t that bad), I notice the shakiness it induces a little bit before my breathing gets easier. Wouldn’t the asthmatics in this study also notice this effect? That’s not something that could be reproduced with a fake inhaler, so wouldn’t that mess with the randomization?
Last year I had bronchitis and my wheezing just wouldn’t stop, so my doctor prescribed a few days of prednisone. I realized that I was feeling worse than usual so I finally went to the local allergy/asthma docs and they did a complete study and prescribed Advair for me. Over a couple of weeks I started to feel better, and the objective measures (peak flow meter) confirmed this. I can now climb hills more easily and take longer to get out of breath. The thing is, I wouldn’t have gone to the docs if I hadn’t started to feel worse than usual, even though my “usual” really wasn’t normal. It’s easy to get used to feeling not quite right without realizing that something’s wrong. It seems to me that the fake treatment in this study took advantage of this all too human tendency.
I wish the doctors who tried to spin the failure of their study realized that their spin can actually endanger people’s lives. It occurs to me that the journal should have published the study without the spin – as it is, it’s just propagating this kind of nonsense.
Am I missing something or is their Figure 4 using a scale from 0 to 100% improvement, while both the caption and the text speak of a 0 to 10 points on a visual-analogue scale?
The graph shows percent improvement on the 1-10 scale that the patients rated themselves on. The legend looks fine to me.
The results were interesting (for 39-person trial).
Shithell, I dream of data that clean from a 39-person trial. That data just beautifully shows how ‘feeling better’ and ‘being better’ are so very disconnected. If they were trying to pin the differences on the unreliability of FEV1, they’d have to come up with a convincing reason the data is so clean. (That being said, dynamite plots have to die. With 39 patients – show the data as individual points in box plots. Far, far more informative.)
Very good point Orac makes on the long-term remodeling of the lung during asthma. What were the NEJM smoking when they published that editorial (and how much did it impact their FEV1)?
Subjective endpoints make life so much easier. Lets apply this study to patients with diabetes. How they feel their diabetes is doing is more important than those pesky, inconvenient objective details, like blood sugar.
Chiming in on how easy it can be to miss asthma symptoms until it’s too late. I’ve always had mild asthma, usually only becomes a problem when I exercise after a long period of inactivity. Well, last October, I just had this cold that wouldn’t go away, with a light cough. I figured it was the season and, well, I was 22 weeks pregnant. Somehow it seemed normal to be out of breath. It wasn’t until I was up at 4am, coughing my brains out that I realized something was really wrong. It didn’t even occur to me that it was asthma until I could no longer breathe without extreme effort and my husband was calling up the OB’s emergency line.
And for a little bit of confirmatory anecdata, I recently started having a flareup of my asthma symptoms for no particular reason, since I was taking all my meds and was not around any of my usual triggers. Very puzzling — until I thought to look at the counter on my steroid inhaler. Which was at zero. I switched to a new, full, canister, and whaddya know, after a day or two, problem solved. (And lesson learned). I wish I knew how long that canister was on empty — it would be interesting to know how long the placebo effect took precedence over reality.
That study was poorly reported — but the published article was no less shoddy. It was just shoddiness on a higher and much more dangerous level. I can state unequivocally that I would far rather be treated on my real symptoms than on what I perceive, and vastly prefer my actual medications to placebo.
Odd, I never have any shaking related to albuterol, but then, I only take it so rarely (usually after an unexpected strong cough, that gets me every time) and in definite need for air that I probably block out any side effects until I’m able to breathe again. Advair before exercise and during certain allergy weeks usually keeps me safe.
Wow. I can’t believe Dr. Moerman is suggesting what he is suggesting. Perhaps it sounds good to someone who doesn’t know any better, but I would hope that medical professionals with any asthma experience would see how irresponsible this is. Given how unreliable self-reporting of breathing ability is, it is downright dangerous to wait until the patient feels poorly before treating. The last time I had a major asthma flare-up, by the time I was feeling poorly enough to seek medical attention, I had pneumonia, and it took 6 months to get my asthma back under control. My asthma is fairly mild, and normally well-controlled – I hate to imagine what the outcome would be for someone with more severe asthma.
By the same logic, it makes perfect sense for patients to stop taking their antibiotics or their insulin once they feel better – after all, that’s the only measure that matters, right?
“And for a little bit of confirmatory anecdata, I recently started having a flareup of my asthma symptoms for no particular reason, since I was taking all my meds and was not around any of my usual triggers. Very puzzling — until I thought to look at the counter on my steroid inhaler. Which was at zero. I switched to a new, full, canister, and whaddya know, after a day or two, problem solved.”
But you would’ve done just as well with sham acupuncture.
You need to listen to your anthropology professor and not be a slave to Big Pharma.
Mu — anecdotally, I can say that my grandmother never seems to notice any shaking when she takes her albuterol, while I get shaking so bad I can’t write easily. But then, I have a tremor naturally; it runs in my family. Beta *blockers* can control it (at least, they work for my non-asthmatic relatives who also have the tremor), but as they’d likely interfere with the beta-agonist albuterol, I’ve never even considered trying them.
@Orac:
There seems to be some words missing here:
It seems plausible to me that sham acupuncture was used in this study (even though one might expect it to only be used in studies comparing it with real acupuncture) because Ted Kaptchuk (who is a Doctor of TCM) is into acupuncture, sham or otherwise.
On the topic of anecdotes about downplaying symptoms to oneself, I have a condition that presents similarly to asthma as well as having frequent respiratory infections.
Because I was so used to it, even though I was waking up in the middle of the night needing to kneel on knees and forearms in order to feel like my breathing was unobstructed, it took my partner telling me that she was scared and that she really really thought I should talk to a doctor about getting it more under control to get me to say to my doctor that my symptoms were out of control. I went to a pediatric asthma specialist as a teenager but aged out of it after college and hadn’t gotten around to finding a new specialist because “I’m not having symptoms”.
Well, pain management would probably be the best. Once a physician determines that the pain isn’t sending any further useful warning signals, managing pain via placebo could be an ideal treatment for patients who found it satisfactory.
@Nicole, #1: I agree. If the study was further limited to those who experience exercise induced bronchospasm, exercise spirometry or some other assessment during/after exercise would probably have cut down on the subjective improvements of the placebo groups – the patients would have useful experiences to compare.
Jake (6):
I got nothing of the sort from this study. What I read indicated that the mind is good at being fooled into thinking that healing is taking place when no actual improvment is occuring.
This study repeatedly demonstrates that how the patient “feels” may have next to no correlation with the progress of the patient’s underlying condition (at least in cases of mild to moderate asthma).
@Neta
I guess that explains why sham acupuncture was used. It doesn’t really explain what the point of it was. As it happens the effect of the sham acupuncture placebo was indistinguishable from the inhaler placebo. What conclusion could the study have come to if it was different? What question was the inclusion of the sham acupuncture supposed to answer? That’s what I don’t get.
Orac,
Am glad you wrote on this. I had the same reaction, that asthma, while usually mild, can be life-threatening. One issue is with the NEJM, which published and promoted a study with just 39 patients and got so much press.
(I wrote on this too, http://t.co/Sb7baAR – but more on the ethics of placebos.)
“The quote from the bottom paragraph page 24 of the softback version of The Report with its serious ramifications must fast be made public internationally. Quote: “Denial of general legal availability of life-saving preventive [medicine] is malicious and premeditated and can cause early deaths. By definition and in law, this constitutes Murder UK Homicide US”. The Report exposes far more than this but, that particular law quote is the most serious law quote in the entire Report. Also on p. 24 they clearly state that: all arrests, trials, incarcerations and forfeitures are illegal. They omit to mention that therefore all warrants are also illegal, but they do explicitly state again on page 24 that, the prohibitionists are the Cause of the current pandemic of disease and death on Earth. In fact, all these quotes here deserve immediate international public recognition.”
I’ve read Dr. Moerman’s book on the placebo effect, and I can say that I don’t believe there is any “woo” in it. I was first made aware of it by Ben Goldacre, who cited it in his book “Bad Science,” where he recommended it highly. Not sure I see anything particularly objectionable in his editorial or his other comments quoted, either.
Also, thanks for coming to , Orac. I enjoyed hearing you thoughts on Placebo Medicine Panel.
” And there ain’t no cure for the summertime blues”
Have you tried acupuncture?
Anyone who has practiced medicine can tell you that the placebo effect has a place in practice, along with other non-therapeutic interventions, and that p+lace is in the relief of anxiety. Anxiety is often concomitant with pain, respiratory distress and other symptoms, and reducing anxiety in the short term can have great value. As an asthmatic who has been in the ER a few times with serious episodes and as a former PA, I can tell you that the feeling that someone is there for you and that something is being done can work wonders. That feeling can not and should not take the place of objectively effective therapy, but a patient is much more than a collection of symptoms. Patients may receive the greatest state of the art, science-based, experience-proven treatment possible, but if they have a bad experience with a staff member in the hospital they are not going to remember that they got better; they will remember the indifferent surgeon, the hostile clerk, the inappropriate nurse. Reducing anxiety might mean a friendly pat on the shoulder, encouraging words, a timely cup of tea or something similar, but there are also times when an intramuscular injection of sterile water given in an authoritative manner can work wonders.
@ herr doktor bimler: Oh, surely you jest! It is not likely that I try accupuncture when I can get the same results with toothpicks. My cognitive-therapy-wonk prof would instruct us how to talk ourselves out of said summertime blues, if that didn’t work I would try gin. Or shopping at Burberry’s or Calvin Klein. Really and truly: I believe that CAM procedures are so ineffective that if I’m going to be *throwing money away* at least I’ll have some decent looking clothes to show for it!
Coming in to the discussion late as I have been taking it easy recovering from TAM,
Some advocates of placebo treatment seem to be invoking mind body vitalism for placebos in that they seem to believe a placebo evokes the power of âmind over matterâ to harness the mindâs supposed ability to heal the body through willpower and positive thinking or The Secret.
@Eerily quiet? (#40)
That’s because it doesn’t cure asthma. Okay, if you vape it, it might help a little bit, but I wouldn’t stake my life on it. Smoking… well… let’s face it, inhaling any kind of smoke is Not of the Good, asthmatic or not.
Naturally, as with any substance (natural or man-made) YMMV.
“I guess that explains why sham acupuncture was used. It doesn’t really explain what the point of it was.”
Maybe they were testing whether a placebo treatment closely related to the real treatment (fake inhaler) worked better than an unrelated treatment (sham acupuncture). Like placebo pills versus placebo injections.
What I take from this study is that the two sham treatments had about the same effect on how people felt, i.e. both made about 45% feel better without changing what was objectively going on. This suggests that the details of the placebo treatment aren’t all that important-giving someone an inhaler with nothing in it works about as well as pretending to stick needles in them. Not too promising for the idea that one can maximize placebo effect.
I’m also a bit confused by the improvement scale. If I understand correctly, it shows percent of people who felt better per self reports on a scale of 1-10. But was the amount of improvement the same in every case? For example, the graph would look the same if 50% of people who got albuterol said their symptoms resolved completely and 45% of people getting placebo said they improved by 2 as vice versa. So all the scale really says is that people felt better with both but not how much better they felt. This makes the finding even less impressive.
Here’s another example to compare. Many advocates of a fruitarian or breatharian diet report feeling light and energetic, better than they ever have before. The only problem is that their bodies are really in a state of starvation, which is, ultimately, not at all good for health. So, eating a good, balanced diet only deals with silly objective things like good nutrition, but fruitarian/breatharian diets make a person feel just smashing! Clearly, then, the latter is what people should choose, according to Moerman, Wechsler and Kaptchuk’s logic.
An oddity of this study just occurred to me. How was the placebo acupuncture explained in the consent form? Since there was no “real” acupuncture in the study, were subjects informed that they would all receive sham acupuncture? The paper says that acupuncture treatments were single-blinded (patients didn’t know, investigator did know).
The paper links to a more detailed protocol which says this:
“They will be informed that they may receive several strengths of active or placebo bronchodilating medication and active or placebo acupuncture…”
Later it says this:
“subjects will be instructed that they will receive one of three different acupuncture point combinations that may
or may not be effective for asthma…”
A full-disclosure informed consent would explain that all patients would receive sham acupuncture. This protocol involved a bit of deception, since patients were told they might receive active acupuncture. Deception in a research protocol can be allowed under special circumstances, but requires very strong justification by the investigator. It would usually require that the study could not be done without the deception. In this case the deception could have been avoided by including an active acupuncture treatment arm.
This is of some importance in interpreting the study results. The placebo effect is likely to be larger for subjects who are told they will receive active treatment, vs subjects who believe they are being randomized to real or sham treatment.
Why, then, did the investigators not include an acupuncture arm in the study? An additional arm does increase the size, cost, and complexity of the study, and well as weaken the statistical power. I’m not sure this would pass muster as a justification for deception. Most likely, the omission of this group was to avoid the likely, but inconvenient conclusion that real acupuncture was no better than sham for any subjective, or objective endpoint.
please excuse typo in my previous post:
A full-disclosure informed consent would explain that all patients would receive sham acupuncture. This protocol involved a bit of deception, since patients were told they
mightwould receive active acupuncture.@Mu: I’m a moderate asthmatic. I’m well-controlled now, so I can notice even a 10% drop or increase in my lung function, but three years ago, when I was really uncontrolled, I wouldn’t notice shortness of breath until I couldn’t talk at all anymore. I relied on my peak flow meter to detect attacks by using it four times a day plus whenever I noticed symptoms or someone commented on them, because I couldn’t percieve one coming on at all.
You’d think having frequent attacks would make you more aware of one coming on, but actually the opposite occurs: you get used to crappy breathing and it becomes normal.
@wholly father
My suspicion was that there was an acupuncture arm that for some reason was not reported in the final paper, but I was wrong. Looking at clinicaltrials.gov I found this. “The investigators hypothesize that different placebos will have different effects on subjective and objective asthma outcomes compared with actual therapy and natural history.”
So that explains the question the researchers were trying to answer. It does look as if they did mislead the subjects, though telling someone they might or might not get acupuncture when they definitely would not doesn’t seem like a serious ethical issue to me.
Krebiozen,
I shared your suspicion about the existence of an undisclosed acupuncture arm, but the protocol and clinical trials.gov indicate that it was not the case.
Regarding the issue of deception, the 2 quotes from the protocol tell a slightly different version of what the patients were told. One of the basic principles of informed consent is full disclosure of what patients will be subject to in a study.
I don’t know what the consent actually said, but telling someone that they may or may not receive a treatment, when it is predetermined that they will not receive it is not completely honest disclosure. Deception in research is a slippery slope. These little deceptions are (and should be) taken very seriously by IRB’s.
@wholly father and Krebiozen
The IRB definitely should’ve stepped in regarding the consent. If no active acupuncture was being offered, then no subjects should have been told that they might receive real acupuncture. The IRB dropped the ball on this one.
I psorta psense that the previous long spewing of cannabis nonsense was our resident pot-head, Jacob.
Correction: either the IRB dropped the ball, or the researchers hoodwinked the IRB and did not use/follow what was submitted for annual ethical review.
@”Chris”: just be aware that nothing angers Orac more than your taking the name of a regular poster and sockpuppeting with it. Those of us who know Chris know how he posts and THAT AIN’T HIS STYLE, BUCKO.
Quit being a jerk, quit posting your stupid marijuana stuff and go away. I’m trying to stay polite.
OH, and by the way: I’m NOT again the controlled use of medical marijuana, nor do I think usage of marijuana is any worse than some other items that aren’t demonified.
However, you have become boring, sockpuppeting and copy-pasting. You have now hit the killfile and I hope Orac bans you.
Many advocates of a fruitarian or breatharian diet report feeling light and energetic, better than they ever have before.
Similarly, most alcoholics feel wonderful when they drink and awful when they don’t. As you said, there’s a hole or two in this paper’s logic.
Unless the consent form specified that some subjects definitely would receive acupuncture, I don’t see a problem. More likely, the consent form told the subjects that they might or might not receive a range of possible experimental treatments, including acupuncture or sham acupuncture. Sham acupuncture would thus fall under the range of possible treatments that they consented to.
Seems like Kaptchuk has a habit of deceiving his trial subjects. His study claiming to show placebo effects can be utilised without deception was shown to be untrue by Orac. He had deceived his subjects – and apparently himself.
He has achieved something significant, however, with this study. I have seen nothing like such a clear demonstration of the potentially misleading nature of results of studies of the placebo effect which rely entirely on patients’ subjective accounts of outcome. It’s doubly ironic that the non-deceptive placebo study was just such a study.
@trrll and others
I’m actually looking into the ethics of the whole issue of telling subjects they might receive active acupuncture even though not a single one would. The minimal risk of the study suggests that it is probably okay, as long as the subjects were told afterward that there was no active acupuncture arm for anyone. When I find out more, I’ll share what I can.
Funny that in spite of themselves acupuncture researchers are demonstrating that they don’t practice what they preach. Acupuncture isn’t more effective than a placebo as many claim; and as a placebo it isn’t clinically meaningful.
I’m finding this post scary and informative at the same time. A distant relative (my cousin’s cousin) just died suddenly at the age of 31 from what appears to be some sort of non-linear complications of asthma. All of the family’s younger generation is in our late 20s to mid-30s now, so that is extra scary.
@ Todd W
Telling patients that they might receive acupuncture, when, in fact, no one will is deception. The risk is nil, but there are issues here other than risk, and other than blinding the study.
Suppose I tell patients they might receive a dollar for participating in the study, but, in fact, I know that no one will be getting the cash. The dollar may be an inducement for some patients to enter the study. Those patient are being duped. The possibility of receiving free acupuncture might motivate a patient to enter the study. Its not the actual value of the treatment that matters, it is the perceived value to the patient. This is probably not a major issue in this study, but is a consideration.
It is usual to disclose to patients not only what treatments they might receive, but the actual probability of assignment to each treatment (i.e. “you have a 50:50 chance of receiving treatment X or placebo”).
The paper describes acupuncture treatment as being single blinded. The whole idea of blinding treatment when there is only one possible treatment is a bit perverse. It can occur only if deception is involved. The patient must believe he is receiving one of multiple options, otherwise blinding is meaningless.
Deception violates the principle of informed consent. If the patient does not have an accurate understanding of the study, he cannot give informed consent.
There are rare situations in which use of deception may be allowed, but the rationale must be fully justified, and there is usually a requirement for debriefing after the study, and an option for a patient to retroactively withdraw consent. If the patient withdraws consent, his/her data may not be used.
This may be a purely academic discussion. For all we know, the investigators took all the appropriate regulatory steps and precautions.
This is very timely for me, since I have just been diagnosed with adult onset asthma, triggered by a respiratory infection. There’s been some useful stories for me to consider as I get my management plan in order. Including the very scary ones.
I’ve got my peak flow monitor & records going now – objective measures FTW!
@#62: I say this as a fellow asthma patient, not as a doctor: May I recommend asking your doctor about an asthma education program? I’m a lifelong asthmatic, but once I pulled my head out of my young-adult behind and decided that having a hard time keeping up with my much-less-active friends, getting colds at the drop of a hat, getting bronchitis several times a year, and ending up in the ER every month were bad things, it was worth its weight in gold to teach me how to effectively self-manage my condition. Plus, the taxpayers of my province probably love it as it’s saved them several thousand dollars in ER bills. 😀
Other good resources are your country’s Asthma Association and/or society website (Google will find it better for you than I can), Health Central’s Asthma Page, and the About.com Asthma page.
I only offer these recommendations because I remember very clearly how overwhelming and bewildering it can be to be told “So, you have asthma, and here’s a long detailed list of what to do and when, but I’m not really gonna tell you wat the terms I’m throwing around mean nor will I give you reliable websites to go to or write it down so that you can remember it easily.”
Good websites like those ones, I think, can supplement your doctor’s instructions and explanations. But, I’m not a doctor, so don’t take what I say as medical advice. 🙂
Finally, a piece of friendly patient-to-patient advice: Don’t be afraid to be a PITA to your doctor if you’re not adequately controlled. It’s your health. Own it (for good and ill). If I’d figured that out sooner, I probably would’ve saved myself six months of severe, uncontrolled asthma. Good luck and get (or stay) well! 🙂
@wholly father
I managed to find a guidance document from DHHS/Office of Human Research Protections on the use of deception in studies. From their perspective, it is okay to deceive a subject through the use of “authorized deception.” Basically, this is telling the subject up front that some information about the exact treatments they will receive or some other aspect of the study has been altered or withheld from them; in short, “We’re lying to you about some part of the study. If you still want to participate, sign here.” In such circumstances, subjects should be offered the opportunity following participation to learn what the deception was.
OHRP stated, though, that this sort of deception is only acceptable in minimal risk studies where the use of deception is necessary to the design of the study, and that the study could not be done without the deception. It looks to be more common in psych and behavioral studies than in physiological ones. This study sort of combines the two, though: physiological effects (FEV1 levels) and psychological (placebo response). That does not, however, justify the spin put on the results.
My guess is that that is probably what happened here, but it probably should have been mentioned in the paper.
It’s definitely a sticky ethical issue, and one that I think I might look into a little more.
No, when it comes to the ethics of experimental trials, it is all about risk. It sounds like you do not understand the ethical concerns that IRBs oversee. An IRB is charged with protecting experimental subjects from being exposed to risks without their consent. It is not charged with ensuring that all details of the design of the experiment be fully disclosed to experimental subjects, nor that they be informed what treatments other subjects will receive or not receive. There is no general prohibition against deceiving experimental subjects. Administering a placebo is inherently deceptive–it is a treatment that has been intentionally designed to appear to be something other than what it is. But a subject in a placebo controlled experiment understands that they may be subject to that form of deception and has consented to it. Note that in many placebo controlled studies, half of the subjects never receive any active treatment whatsoever. Another common design of drug trials is a “placebo run-in.” With this design, everybody initially receives a placebo, and anybody who exhibits a placebo response at this stage is dismissed from the study. The goal of this is to increase the sensitivity of the study to real drug effects by eliminating “placebo responders” (there is considerable reason to doubt whether it achieves this, but that is another matter). Again, this is considered ethically acceptable, so long as the subjects understand that the treatment they receive may be a placebo.
Of course, an overly rigid requirement of full disclosure of all aspects of an experiment would make placebo controls impossible at all. This would doubtless be welcomed by purveyors of “alternative” therapies, who would be freed from the awkwardness of having to explain to their patients why they are paying for a treatment that is not better than placebo in clinical trials.
Of course, in the case of acupuncture, it is beginning to look like the term “placebo acupuncture” is redundant–evidence is mounting that all acupuncture effects are placebo effects, considering that it doesn’t seem to matter whether the needles are inserted into the “right” or the “wrong” points, or whether they even penetrate the skin at all.
Anyone with asthma will have stories of doing stupid things because “I feel fine”. My latest was when I was visiting my parents this summer, and went for a walk on the cliffs with a friend (at Carnewas, for anyone who knows that part of Cornwall). Despite having black spots in the edge of my vision at rest, I climbed down a staircase to the beach to go boulder-hopping at the tideline. Getting back up the 140-odd steps, then over the cliff-paths back to the carpark, when I had to stop and rest every couple of metres was exciting.
Another thought occurred to me regarding the whole active vs. sham acupuncture deception. Even if people were told ahead of time that they were being deceived, if the deception was not revealed afterward, subjects may go away from this study thinking that acupuncture is an effective treatment for asthma, if they thought that the acupuncture they received was the real deal, such as it is.
The study, to me, highlights the dangers of using placebos for conditions which, if untreated, can worsen and cause more serious complications. The subjective measures show that subjects believed that the placebo treatments were effective. If the researchers did not disabuse them of this notion, they may well have gone away from the study thinking that they do not necessarily need to treat their asthma with albuterol, and that acupuncture may be a dandy alternative.
The thing that jumped out at me on first reading of the article was the fact that they were using acupuncture ( or fake acupuncture) as one of interventions.That seemed to me to already elevate acupuncture to a level that it was worthy of being included in a study measuring response to “asthma treatment”.
Thanks Sarah, and stripey_cat. I’m OK with my doc at the moment. Unfortunately my regular is on holiday (What? How dare he have a life?) but I’m seeing another in the same practice so the records will all be together. I have another appointment to discuss management, and lots of brochures and booklets and a reference to http://www.asthmafoundation.org.au/
It was probably more that acupuncture is a placebo that has a lot of ritual associated with it, and one that still retains a lot of credibility with the public, so the authors may have thought that it might be a “stronger” placebo (there is a substantial literature supporting this idea) than a placebo puffer. In the end, this turned out not to be the case. The fact that they didn’t even bother with “real” acupuncture indicates to me that they didn’t perceive any meaningful distinction between placebo acupuncture and “real” acupuncture.
But if the placebo-ma-thingy is 0.4 more than nothing, it must be 0.4 times as good, right? In your face, math. Woo-hoo!
Another perfectly cromulent post, ORAC.
I apologize if this seems like I am spamming, but Moerman was interviewed on a podcast shortly after his editorial came out, and he further explains his thoughts on the placebo effect.
http://podcasts.jwatch.org/index.php/podcast-126-placebos-and-medical-meaning/2011/07/16/
(Note: I do not necessarily endorse all of his ideas.)
Very informative. I work with Good Days from Chronic Disease Fund, and it is our goal to assist chronic disease sufferers in gaining the treatment they need. By supporting our organization, you could help these patients too! http://www.gooddaysfromcdf.org/
@Krebiozen
Is there any way of knowing if there also was a *real* acupuncture group in the study, the data from which is not included in the published paper? This is a very Conspiratory Theorist thing for me to ask, I know, but I also wonder why *sham* acupuncture was included in this trial. It doesn’t make sense to me to include it, unless you also include *real* acupuncture.
I treat Asthma as an allergist in NE Ohio and just read the study last night. I immediately looked for a blog post about this from Orac and was not disappoionted. Orac’s description of why treating objective finding such as lung obstruction even when the patient doesn’t feel it, is right on. Short term consequences include decrease QOL, inability to participate in activities, and an increased risk for an acute care visit, death. Long term complications include airway remodeling and eventual COPD. The disconnect between symptoms or asthma and lung function is well documented. At least 15% of our patients in a large academic center are considered poor perceivers which means they have no symptoms but their FEV1 is less than 80% of normal with reversibility. That being said the editorial from Moerman was the worst editorial in the NEJM I have ever read. A couple points- I wonder what patient symptom improvement would be if this study was done in the ED with symptomatic patients? The numbers in the study are low because it is very hard to find patients who show significant (>12%) reversibility in FEV1 even at our center where 2/3 of patients are moderate to severe asthmatics. That is because patients who have this on spirometry should be on inhaled steroids +/- LABA (Salmeterol). We only see that in newly diagnosed patients or those with acute exacerbations. These patients were allowed to go untreated or undertreated throughout the duration of the study. The treatment of asthma is not albuterol it is oral steroids during an exacerbation and inhaled steroids to prevent that exacerbation. Letting people think they are fine despite reversible airway obstruction is malpractice and/or negligence. Next, it is possible that real accupuncture was not used because the results would show no evidence of benefit (Conspiracy as above). I cannot wait to see what the comments are for this article in the NEJM.
The mention of asthma as a purportedly scientifically understood and treated disease shows the reliance on a how many angels on the head of a pin type of argument here, betraying the aims of the authors. The extensive scientific writings on inspiratory muscle training and the widespread use of the respective appliances clearly indicates not only that asthma symptoms may be eliminated by such training but also that the muscle detraining effects of asthma drugs must be responsible for the epidemic. Furthermore all too relevant is the utter absence of the least serious enquiry about causation due to treatment. Obviously anyone afflicted by the disorder should consult a physician aware of the developments. RF