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Asthma, placebo, and how not to kill your patients

A number of years ago I was walking along Lake Michigan with a friend (a fellow medical resident) when she turned to me and said, “are you wheezing?  Do you have asthma?”  I had always been physically active and assumed my breathlessness while walking down the trail was due to the thirty extra pounds of pizza and doughnuts I’d acquired during residency.  But she was right: I was wheezing and breathless and it didn’t feel good at all.  I made an appointment with one of the hospital’s lung docs who took a good history, did a physical, and ran some pulmonary function tests.  And I did have asthma.  And it felt much, much better when I used proper medication, a feeling confirmed by my improving lung function tests. (Not too surprisingly, the asthma got even better when I lost 40 lbs and started treatment for my acid reflux.)

I still get mild asthma symptoms from time to time, especially when I get sick, but for many others, the picture isn’t so pretty.  Asthma kills at least a quarter of a million people every year around the world.   If you’ve ever worked in an ER and seen a kid with a bad asthma attack, you’ve earned a healthy respect for the disease.  If you’ve ever watched your own kid gasping for breath, begging you to make it better, you’ve learned to fear it.

As our understanding of asthma has improved, so has our ability to treat it (an ability that is strongly linked to a patient’s socio-economic status.  Mortality has been rising despite the discovery of better treatments.  Wait: let’s pull this out of the parentheses…)…  Asthma deaths and hospitalizations are largely preventable, and disproportionately affect Black and Hispanic Americans. We know how to treat the disease asthma, but don’t know how to treat the people who are affected most.

We understand that asthma is not just a tightening of the airways but also an inflammation that can cause long-term damage.   Not only can we treat asthma, but we have objective ways of measuring how well our patients are doing.   It’s easy and inexpensive to measure airway obstruction and response to medications.  We know what works.
For this reason, a new study in the New England Journal of Medicine seems both wise and foolish.

(I thought I was so on the ball.  I really did. But while I was busy riding my bike, playing with my kid, and looking at rentals with my wife, David Gorski and my other medical blogger pals were out in Las Vegas at TAM discussing the very study I wanted to tell you about.)

The study, called “Active albuterol or placebo, sham acupuncture, or no intervention in asthma,” was done for reasons that are not clear to me. It may have been done not to test the effectiveness of asthma therapy but to look at what a “placebo” might really be or do.  At least, I think that was the idea.  When reading the abstract and full text, it’s not actually clear why the study was done.  At first it seems as if it were done to see why asthmatics treated with placebo improve:

In prospective experimental studies in patients with asthma, it is difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention.

Why ask such a question? We know that poorly-treated asthma is deadly, and well treated asthma much less so.  Why do we care about placebo effects here?  The authors explain further:

Placebo effects (i.e., benefits resulting from simulated treatment or the experience of receiving care) are reported to improve signs and symptoms of many diseases in clinical trials and in clinical practice. On this basis, the accepted standards for clinical-trial design specify that the effects of active treatment should ideally be compared with the effects of placebo. Despite this common practice, it is unclear whether placebo effects observed in clinical trials (or those that presumably occur in clinical care) influence both objective and subjective outcomes and whether placebo effects differ from the natural course of disease or regression to the mean.

In other words, the authors want to know what placebos actually do to real people, and they chose asthmatics because they are easy to study (there are symptom-assessment tools for subjective data and spirometry for objective data).   This makes asthma both the right and wrong choice for the study.  It’s an excellent model to assess the affect of placebo, but one in which the use of placebo is hard to justify on an ethical basis.

Not surprisingly, they found that “doing something” worked better than doing nothing.  More specifically, they found that any placebo will make a patient feel subjectively better than doing nothing at all.   They also found that all three placebos (sham acupuncture, fake inhaled medicine, and simply being enrolled in the study without treatment) improved objective measures of lung function, but not nearly as much as real medicine (in fact, not much at all).

In other words, simply attending to a patient makes them feel better.  But to get a significant objective improvement (in asthma at least) you must also give them real medicine.  Real medicine comprises both active medications and attending to the patient.  There is no separate “placebo” that can be given to treat asthma effectively.

This is actually a quite beautiful study.  It demonstrates that “placebo effect” is not the same as a real treatment, that real treatment always includes whatever benefit placebo provides, and that placebo is mostly an effect on subjective rather than objective measures of health.  You can’t fix asthma with placebo, only with real treatment.  But we’ve already known that from decades of studying asthma.  So what other justification is there for doing this study?

Our research has important implications both for the treatment of asthma and for clinical-trial design in general. Many patients with asthma have symptoms that remain uncontrolled, and the discrepancy between objective pulmonary function and patients’ self-reports noted in this study suggests that subjective improvement in asthma should be interpreted with caution and that objective outcomes should be more heavily relied on for optimal asthma care. 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. Although placebos remain an essential component of clinical trials to validate objective findings, assessment of the course of the disease without treatment, if medically appropriate, is essential in the evaluation of patient-reported outcomes. (Emphasis mine, PalMD)

This is folly.  First, we have a huge literature on quality of life metrics in asthma.  Huge.  And we also know that objective changes in asthma are what save patients’ lives.  Yes, I care how my patient feels, but it is not more “clinically relevant” than how they are actually doing physiologically.  Both are important, but not equal.  And the idea that comparing active treatment to placebo is not ideal is not new to researchers.  It’s simply that following the natural history of the disease as a “control” is not usually appropriate (cf. Tuskegee syphilis experiment).

No good clinician would consider treating an asthmatic with placebo.  Improper treatment of asthma leads to debility and death.  This study chose mild asthmatics, but I still feel very uncomfortable with the ethics of the study design.  Rather than using a disease we know how to treat to study placebo, we should be finding ways to get treatment to the millions of people who aren’t getting it.

References

Wechsler ME, Kelley JM, Boyd IO, Dutile S, Marigowda G, Kirsch I, Israel E, & Kaptchuk TJ (2011). Active albuterol or placebo, sham acupuncture, or no intervention in asthma. The New England journal of medicine, 365 (2), 119-26 PMID: 21751905

Posted in: Science and Medicine

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23 thoughts on “Asthma, placebo, and how not to kill your patients

  1. daedalus2u says:

    It is curious that they did not put the final open-label use of albuterol in any of the charts. They report that at the final visit, the open-label albuterol had a 20% effect on FEV1, similar to the 21.1% effect in the open-label screening visit but the minimum response was 12% in the screening visit. In the study apparently the average response was 21.9%. In the double blind albuterol leg of the trial, only 90 of 117 trials were above 12%, but the mean was still 21.1% whereas in the screening first visit 39 of 39 trials were above 12% but the mean was only 21.1%. I am curious how you could have a mean of 21.1 with 23% below 12% and still have a standard error of ~2%? If you have a normal distribution, you can’t have 23% more than one sigma below the mean. If the distribution is highly skewed, it is disingenuous to use statistics like this.

    It is curious the way they used to handle the data, they took a base-line FEV1 measurement, administered the treatment and then did FEV1 measurements every 20 minutes for 2 hours. Then they took the maximum FEV1 during that time as the value to compare. What is the normal scatter in FEV1 when administered every 20 minutes? In the screening trial, did they do a FEV1 every 20 minutes? The screening FEV1 shows an improvement of 21.9 +/- 9.9 % (standard deviation). Their blinded albuterol trial FEV1 show 20.1 +/- 2 (standard error estimated by eye from figure 3). If you add the 2% standard error from the albuterol trials to the 7% effect of the non-drug trials, do you get about the ~10% of the standard deviation of the screening trial? Is the “no treatment” effect of 7.1% really just regression to the mean? Is the placebo inhaler effect really 7.5 – 7.1 or 0.4%? Is the acupuncture effect really 0.2%?

    The standard error is usually calculated by taking the standard deviation and dividing by the square root of n. When n = 7 (FEV1 tests every 20 minutes for 2 hours),

    Is it appropriate to take the maximum FEV1 as representative of the “treatment effect”? Or would the mean value be better? If there is scatter in the data, taking the maximum adds that scatter to the “treatment effect” where taking the mean subtracts the scatter from the “treatment effect”. Of course if you want your “analysis” to treat the scatter as “data”, then you do what they did, and get the results they got.

    Because they mention exhaled NO, I looked into that a little more, and it is likely that increased exhaled NO is part of the therapeutic effect of the inhaled steroids. They showed pretty clearly an increase in exhaled NO with inhaled steroids and a decrease with everything else. A major adverse symptom of asthma is airway hyperresponsiveness (AHR), which is perhaps even more important that FEV1 because it is AHR that controls the progression of lung damage due to the chronic inflammation of asthma.

    NO does reduce mast cell hyperresponsiveness. This is part of the normal regulation of the immune system, where the respiratory burst decreases the local NO level which potentiates mast cell degranulation. This is why low NO is an inflammatory state (low NO activates NFkB) and why an inflammatory state causes low NO. Increasing NO levels in the lung is very likely is necessary to turn-down/prevent the inflammation and the tissue remodeling that causes the long term adverse effects of asthma. These long term effects are more important than short-term increase in FEV1 or subjective improvement in breathing.

    Increased inflammation can increase exhaled NO also, but during inflammation there is decreased NO in the inflamed tissues. It is the NO in the tissues that matters, not what can be measured externally. You can have both increased exhaled NO due to inflammation and decreased NO in the inflamed tissues.

    I see several dangers (yes dangers) from the kind of thinking used in this study. Subjective feelings of improvement did not correlate with objective measures of FEV1, or exhaled NO. First, using treatments to try and achieve subjective feelings of improvement in the absence of actual improvement will very likely exacerbate the disconnect between actual lung status and subjective patient feelings of lung status (that is a bad thing). This will decrease the patient’s ability to self-monitor their lung status. Since the asthmatic state can exhibit positive feedback leading to fatal asthma attacks, these will become more common because patients will have reduced ability to catch them and treat them earlier. Second, because the patients will be in a non-improved inflammatory state longer, the lung remodeling due to inflammation will proceed faster and the long term decline will be faster and more severe.

    I see these as really bad and really dangerous editorial and article. I think both should have warning labels or better, be retracted.

  2. Tell it like it is says:

    “It is difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention.”

    followed by:

    “Not surprisingly, they found that “doing something” worked better than doing nothing.”

    clearly demonstrates that it is ‘not’ “difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention.”.

    Moving on.

    “More specifically, they found that any placebo will make a patient feel subjectively better than doing nothing at all.”

    Please define ‘subjectively better’. Is this a term which means ‘I have believe the HS and I am now deluded’?

    On “sham acupuncture”, is the needle ‘virtual’ – i.e. I only see the needle that has not penetrated my skin and now sticking out of my body in my minds eye?

    And we have: “They also found that all three placebos (sham acupuncture, fake inhaled medicine, and simply being enrolled in the study without treatment) improved objective measures of lung function, but not nearly as much as real medicine (in fact, not much at all).”

    “in fact, not much at all “ establishes that both the treatments AND the data is erroneous.

    Please hear me out.

    It sounds like the study was carried out using ‘statistical analyses’.

    In ALL evaluations, ‘whatever’ the method adopted, we must avoid ‘false positives’ AND ‘false negatives’.

    A ‘false positive’ can be understood as follows: “You have tested POSITIVE for cancer – but you may not have it.”

    A ‘false negative’ can be understood as follows: “You have tested NEGATIVE for cancer but you MAY have it and will therefore require treatment that if delayed could cause early termination of your life (by the way – untreated asthma is a life-shortener too).

    Which is the worst of the two errors?

    What I am asking is: Would you sooner have the trauma of being told that you MAY have cancer (false positive), or be told that you may NOT have cancer – and then die a painful and humiliating death from it?

    Statisticians always but ALWAYS take the ‘false positive’ stance – and because of the gross mathematical errors within the method, ‘statistic analysis’ ALWAYS creates ‘false positive’ errors. But in ‘my’ book, a false NEGATIVE is FAR worse – but statistics cannot detect them. As an aside, Bayes theorem CAN – ask Apple inc.

    So now we have a ‘double-blind’ situation, viz:

    The error that statistics creates (i.e. it ‘errs’ to ‘false positive’)

    and

    the HARM statistics CAUSES by NOT identifying the more serious ‘false negative’ ‘error’.

    Pressing on: “This makes asthma both the right and wrong choice for the study. It’s an excellent model to assess the affect of placebo, but one in which the use of placebo is hard to justify on an ethical basis.”

    What was carried out has already assessed the affect of placebo, and in your own words “in fact, not much at all”, conclusively proved that administering a placebo is a total waste of time – especially the placebo “enrolled in the study without treatment”.

    All of this is SUBJECTIVE NONSENSE and not OBJECTIVE ASSESSMENT and does not serve man one jot.

    Should you, or anyone else request it, I will post how to carry out an OBJECTIVE ASSESSMENT that uses fractional factorial evaluation. What is amazing about the method is that it gives the correct answer – even though you haven’t tested for it. How good is THAT?

  3. Tell it like it is says:

    Is it me? Lets start your week off with a smile and have a quiz to find out.

    1 What drink is made from beans found in the poo of the tree-climbing civet cat?

    a) Tea
    b) Coffee
    c) Chocolate

    2 What did a Tudor mum rub on baby’s gums to help relieve teething pain?

    a) A dead hare
    b) A wet sardine
    c) A frozen mouse

    3 What is unusual about people with situs invertus?

    a) Their bum cheeks are upside down
    b) Their body hair grows inwards
    c) Their organs are on the opposite side of their body

    4 Which liquid was used as a blood plasma in World War 2?

    a) Lemonade
    b) Coconut juice
    c) Grape juice

    5 What does the Komodo Dragon giant lizard occasionally eat?

    a) Its own poo
    b) Its toenails
    c) Human corpses

    6 What super-animal have genetic scientists recently created?

    a) A mighty mouse
    b) A super gerbil
    c) A power pig

    7 Which of these is a symptom of the deadly ebola virus?

    a) Green urine
    b) Black vomit
    c) Purple ear wax

    Post your responses as a seven letter sequence and I will post the answers later.

    Have fun.

    TILLIS

  4. Peter Lipson says:

    Sorry, that all left me rather speechless.

    If you have questions about the validity of various spirotmetry data and what they mean, there are many online references.

  5. Wholly Father says:

    In some diseases, patients can use symptoms to monitor the status of their disease, in others symptoms are not a reliable indicator of disease status. In diabetes, for instance, symptoms are a poor indicator of blood sugar, except at the far extremes. If I make an asymptomatic diabetic feel their blood sugar is better controlled, even though it is not, might that not have a paradoxical harmful effect? They may be less careful about their diet, or less vigilant about monitoring their blood sugar, and less sensitive to subtle symptoms of a real problem.

    In in a disease, like asthma, where a patients “intuition” about the status of their disease based on symptoms is important, a strategy of placebo therapy to treat the feelings, but not the disease could a particularly dangerous. A false sense of security is a dubious objective.

  6. Josie says:

    Interesting comment WF. It got me thinking of other examples.

    Hypertension might be similar to your diabetes example. My grandfather would go off his medication because he saw no overt effect and he ‘felt fine’. A placebo treatment could push a patient to ‘feel fine’ but allow the underlying disease to progress.

    Another example where it’s important for a person to understand symptoms is migraines. I know I’m getting a migraine if I start going blind; the edges of my vision go black and then progressively my entire field of view follows. It’s a very reliable symptom and indicator of the pain to come. Although I seriously doubt any placebo therapy would alleviate my vision problem or the following headache. I just know I need to get off the road ASAP if I am driving or riding.

  7. daedalus2u says:

    WF, I completely agree, treating the symptoms with placebos which only affect subjective feelings is not helping. It could easily lead to more severe and even fatal problems which CAM practitioners are not equipped to either understand, diagnose or treat.

  8. Wholly Father says:

    Irony #1: CAM advocates constantly decry “Western Medicine” for only treating symptoms, and not the disease. The authors’ interpretation of this study advocates the attitude treating the disease is secondary to treating the symptoms.

    Irony #2: The touchy feely side of CAM wants to help patients be in touch with their bodies so they can better understand various states of health and disease. This interpretation of this study argues for the disassociation of symptoms from useful insight they might give the patient about the status of their disease.

  9. Calli Arcale says:

    Wholly Father, I wholly agree. I said as much in Dr Gorski’s post on the same study. What this study showed me, more plainly than anything else, is that it is extremely dangerous to treat asthma with placebo, because the patient will have no idea that they are actually not well and are in fact getting worse until they have gotten a LOT worse, by which time some real damage may have been done.

    This is seen more commonly in cancer treatment, where from time to time one hears about a patient who was declared terminal switch to some form of alternative medicine. In too many cases, the patient is praising the alt med for curing their cancer right up until the time the cancer kills them. AIDS is another one that gets a lot of that. It’s very tragic.

  10. Tell it like it is says:

    @ Peter Lipson Hi Dr Lipson

    Loved your comment about being breathless – brilliant!

    I made two points.

    One: that administering a placebo is a total waste of time – nothing more – and that I was constructively highlighting that this fact is revealed in your article. I may have appeared flippant to trigger a ‘fifth wall’ response to set the table alight so as to stimulate a proper debate – but as you read, most commentators who bothered to comment agree with me.

    Two: I was attempting to show the dangers associated with ignoring ‘false negatives’ as Calli Arcale beautifully illustrates in their comment “In too many cases, the patient is praising the alt med for curing their cancer right up until the time the cancer kills them. AIDS is another one that gets a lot of that.”

    As the compassionate person said “It’s very tragic.”.

    To me its not just tragic – its avoidable. We have four drivers:

    - Hazardous attitudes (i.e. self righteousness; invincible; anti-authority; complacent; impulsive; and cavalier.)
    - Disaster incubation (an accident waiting to happen)
    - Accident chain (break ANY link and the accident is avoided)
    - Belief in horse sh!t because of a) seeking HOPE; b) exposure to hazardous attitudes when treatment is sought; c) cost; d charlatans; e) lack of education; f) ineffective education (i.e. what is communicated is not believed)

    Permit me to illustrate my two points – and please please see this for what it, is as I am in no way attempting to be condescending.

    On spirometry. Whilst I appreciate that spirograms are a very useful diagnostic tool to both predict onset of a pulmonary condition, and aid the assessment of various breathing disorders such as cystic fibrosis, COPD, and asthma (when you are fortunate enough to catch an attack); carrying out the forced volume vital capacity manoeuvre is heavily dependent on patient cooperation and effort, and the practitioners’ assessment of the results.

    On practitioner assessment: the FEV1% measure is the ratio of FEV1/FVC. As with any ratio – for example, the side opposite the angle divided by the hypotenuse ‘ratio’ used to determine the sine of the said angle in a right-angled triangle, the ‘ratio’ will always remain the same – irrespective of the ‘size’ of the thing under evaluation.

    To clarify: a right-angled triangle with a base of 4 units, an opposite of 3 units, and a hypotenuse of 5 units will always yield the same sine value (3/5 = 0.6) whether the triangle is measured in centimetres, inches, or miles because the ‘proportions’ remain the same.

    As FEV1 and FVC generally both reduce ‘proportionately’ with age or illness, the FEV1% value will have a ‘tendency’ to read ‘normal’ or may even give an ‘increased’ value as a result of decreased lung compliance – i.e. the test will generate a ‘false positive’ even though the patient has an ailment that they do not yet know they have.

    Because the forced volume vital capacity manoeuvre is heavily dependent on patient cooperation and effort, the results obtained will have a ‘tendency’ to create a ‘false negative’ – hence the reason for the > 80% ‘trip value’ (AKA trip point) to ‘accept’ that such a reduction from the computed tables is acceptable – but the this may NOT be the case and that person comes under the banner of “It’s very tragic.”.

    Equally, whilst sex, height, age, and ethnicity are accommodated within the evaluation tables, there is no ‘adjuster’ for fitness of the lungs – an asthmatic trumpet player or an athlete will have the capability and ‘tendency’ to ‘overblow’ – so now we have an ailing patient registering a superb set of lungs – and a ‘false positive’ ensues.

    Here is a useful article which I trust will aid others in the comprehension of spirometry.

    http://www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/COPD/COPD%20Consortium/spirometry_in_practice051.pdf

  11. libby says:

    Perhaps it was folly by one physician, but when my 4 year old son had asthma he was given a cortico-steroid puffer that slightly reduced his asthma, but negatively affected his general health.

    Modern medicine at the time seemed to have no other options, which prompted my spouse and I to head for an alternative treatment that appeared to permanently solve the problem in a short period.

    It’s difficult to imagine a 4 year old responding to a placebo. Something happened that was positive and possibly saved his life.

    My question would be, what modern medical strategies are now in place to deal with a condition like my son’s, who was not responding well to inhalers and whose general health was taking such a serious turn for the worse?

  12. WilliamLawrenceUtridge says:

    A common “justification” for homeopathy is that it works on children and animals, because “how could they respond to a placebo when they don’t understand it?” There has been an answer for years – when the parent/owner appears soothed, when they appear to stop worrying, when they state that this will help (even with animals there is a reaction to the tone of voice), it can evoke a placebo effect. Even the sense of doing anything can be helpful (it’s called emotion-focussed coping). Science has known of this flaw for years, which is why the gold standard is a double-blind test. When the researcher doesn’t know which treatment is real and which is a sham, their ability to project confidence, even unconsciously, should be the same for both interventions.

    Libby, you may find it difficult to imagine an explanation for your son’s asthma appearing to disappear. There are many. There are conditions which can look like asthma, particularly to nonspecialists. In the case of genuine asthma, there are triggers that can wax and wane – particularly something like allergies which can appear and disappear in both children and adults. You keep saying “appeared to” but fail to acknowledge other explanations exist; you’re falling prey to the same fallacy that most antivaxers do – post hoc ergo propter hoc. Just because two things happen at the same time doesn’t mean one thing caused another.

    As for what strategies exist, your son could have tried a different medication, avoided allergens, or confirmed that your son had asthma in the first place. You may benefit from reading the NIH page on asthma, which states on the “How Is Asthma Treated and Controlled?
    ” page:

    It’s hard to diagnose asthma in children younger than 5 years.

    So before crowing about how a CAM treatment saved your child, you may want to ponder whether your child needed saving.

    Finally, I would point out that if it is indeed asthma, and is currently uncontrolled, there are considerable dangers. Asthma can turn deadly very, very quickly. See this article from the Seattle Weekly about a girl who died of uncontrolled asthma despite being under the “care” of a naturopath (credit goes to Dr. Atwood for pointing that article out).

  13. WilliamLawrenceUtridge says:

    Agh, the Seattle Weekly article failed to link:

    http://www.seattleweekly.com/2005-06-08/news/death-by-natural-causes.php/

    Excellent article.

  14. Science Based Med Student says:

    Josie’s migraine comment reminds me of a lecture I heard last week that made me cringe. I just had a cardiology professor express a similar understanding of the use of placebo to treat migraines in my clinical research class. He explained that if you give migraine patients a placebo, more than a 1/3 will simply get better on their own and to consider this when treating migraine patients. When I asked him to clarify this (was there a specific study he was referring to, what does “get better” mean, what were the end points used to reach this “get better” conclusion, where these improvements subjective?), he fumbled for a while and then said that the patients experienced a reduction in reported pain, but that they still had pain. Being that I seek treatment for the occasional 10 out of 10 migraine pain, having a reduction in my 10 out of 10 pain (while an improvement) does not equal “getting better” to me (a 7 or 8 out of 10 is still pretty horrific) or provide a clinically satisfactory outcome. This seemed like a gross overstatement of the benefit of placebo alone as a treatment for migraines. It is crazy to me that anyone would suggest placebos treatments to treat asthma or migraines, when there are more effective and established treatments for such conditions. I completely agree with Dr. Lipson that how my patients subjectively feel is important, but not more important than how they are physically doing. Wouldn’t it be great if the minds behind Science-Based Medicine could develop a science-based medicine research curriculum for medical schools?

  15. nybgrus says:

    I’ve been discussing this NEJM article and the ensuing posts and comments with some of my classmates. A few are very science based and extremely up on the literature and so we work on the concept of placebo, the ethics involved, what good we can pull from the study, and how wrong (and why) Moerman is.

    Some however, are not quite a rigorously science based and I have come across the “You shouldn’t treat a lab value, you should treat your patient” argument. The first time I heard it I was stymied for a minute. Until I realized that was an argument of false dichotomous thinking. Just because you do treat the lab value, doesn’t mean you can’t also treat the patient. And that is the point – the two cannot be divorced from each other. Sometimes the subjective will outweigh the objective, sometimes vice versa. However, in no circumstance (save where we actually do not have any reliable objective measure) should we ever treat one to the exclusion of the other. Most of the time, it is a sliding scale somewhere in the middle but I can think of a number of cases where you will doggedly pursue an objective value even if your patient feels 100% fine. (An incidental finding of a brain tumor – or any tumor for that matter? A silent infarct? Hypertension?)

  16. woo-fu says:

    Rather than using a disease we know how to treat to study placebo, we should be finding ways to get treatment to the millions of people who aren’t getting it.

    @PL–an inspired piece, indeed, and one that deserves attention. Increasingly poor air quality and more asthma warnings from my local weather station underscore this need. And for me, it’s personal.

    I hope you will excuse this anecdote, as it does demonstrate, albeit somewhat minimally, my own accidental placebo experiment with asthma.

    I was in the middle of an asthma attack and grabbed my albuterol, took my usual number of puffs, but didn’t really feel much better. I thought my instincts must be off, but what was off was the inhaler. I’d grabbed an old one by mistake. (The bigger mistake was not immediately throwing out the old inhaler.) In my haste I didn’t notice because there was still a bit of propellant in the canister which I felt when I shook it.

    That should have been a perfect opportunity for me to experience a placebo effect, but there was none. I just kept feeling worse until I discovered the error, found my active container and used it appropriately.

    @D2U

    using treatments to try and achieve subjective feelings of improvement in the absence of actual improvement will very likely exacerbate the disconnect between actual lung status and subjective patient feelings of lung status (that is a bad thing). This will decrease the patient’s ability to self-monitor their lung status.

    No kidding! I thought something was off with my sense of lung function until I realized there was too little active medicine left for me to have felt any improvement.

    @libby

    when my 4 year old son had asthma he was given a cortico-steroid puffer that slightly reduced his asthma, but negatively affected his general health

    I have problems with steroid inhalers, too. In some people they can aggravate other conditions. I have also had my asthma symptoms wax and wane, disappearing for long stretches of time, but I keep my albuterol handy because for the rare times I get attacks, I still need to breathe.

    This is not meant to be critical, but it is important to make sure your child’s lung function is at least monitored on a regular basis to make sure they aren’t having any problems. I’m sure you already take this into consideration, but I just wanted to stress the importance. And, just in case, if your child does have asthma, do consider non-steroidal inhalers as another option.

  17. Tell it like it is says:

    @ WilliamLaurenceUtridge

    Hi William

    You raise several noteworthy points.

    “When the parent/owner appears soothed, when they appear to stop worrying … it can evoke a placebo effect.”

    From this we may determine that the child becomes stressed because the guardians of the child are stressed – which, in turn, could provoke an asthma attack – and when guardian stress-levels drop (for whatever reason) then that child’s stress level ‘also’ drops, and this reduces the ‘likelihood’ of an asthma attack occurring.

    Because the ‘‘mean-time’ between incidents (asthma attacks)’ (i.e. ‘elapsed time since the ‘beginning of treatment marker’ divided by ‘number of incidents’) drops, the stakeholders are deluded into believing it was the placebo that improved wellness and wellbeing – when it was the reduction in stress levels that brought about the perceived ‘improvement’.

    While soothing the guardian may be of its self sound advice, the placebo does not cure the sufferer and only exacerbates the delusion problem.

    This prompts examination of your statement “the gold standard is a double-blind test”.

    You state “When the researcher doesn’t know which treatment is real and which is a sham, their ability to project confidence, even unconsciously, should be the same for both interventions”. Now we are back to square one – delusion – only this time we are deluding the practitioners as well as the respondents. This is ‘fools-gold’.

    All birds have feathers

    Ducks have feathers

    Therefore

    All birds are ducks

  18. Tell it like it is says:

    @ Science Based Med Student

    “Wouldn’t it be great if the minds behind Science-Based Medicine could develop a science-based medicine research curriculum for medical schools?”

    Scientists are exploring the unknown and there is a need to paint a trail between research and outcome. If we knew the answers there would be no need to carry out experiments (particularly on primates) – plus – much of what we determine is no more than informed guesses.

    There is a real need for research institutions and the funding agencies to provide the infrastructure for academic scientists to be able to more effectively translate their work into a medical or other broad social environment without being penalised because what was carried out produced a ‘negative’ or inconclusive result.

    A point to bear in mind is that ‘negative results’ are not results of ‘no value’; and they actually ‘add’ considerable value if such results are made known; hence, such results should be published so that others may know. This needs to be part of the change if we are to make progress.

    One of the obstacles to this change is that if one achieves a negative result and wishes to communicate that fact, very few respected journals – publications that could bring positive impact – would publish it. This stance needs to change.

    A second obstacle is the number of worthless studies carried out that do not serve mankind and may have been carried out for self-serving purposes. This overburdens and confuses the stakeholders and the people at large, and creates fog – which is what the charlatan will use to hawk their wares.

    Another obstacle is the way that the results are derived can be dubious, and the method of evaluation may be at best biased, and at worst, flawed, and so other methods of evaluation such as fractional factorial experiments should be applied in tandem to establish and concur findings.

    A further obstacle is that publishing negative work reduces your chances of obtaining funding to further the research. This is debilitating and pointless.

    For the first-rate scientist who asks clear-cut questions for which positive ‘and’ negative results are equally valuable, we must have a mechanism in place that provides a record for the community and does not scupper funding, so that a) futile experiments are not repeated, and b) we are prompted to seek out a better experimental model.

    From your remarks, I would question the credentials of Cardiology Professor and, like you, I would have taken them to task.

  19. Tell it like it is says:

    Here are the answers to my quiz. Were you inquisitively quizzical or quisitively inquizzical?

    I deliberately designed my quiz to highlight several viewpoints that reoccur in this and all discussions I have participated in thus far.

    1 = B Here I was illustrating what Ludwig Wittgenstein calls “bewitching language games” designed to ‘ensnare the ‘mark’.

    2 = A Here I show the ludicrousness of a ‘belief’. Do ‘you’ believe rubbing a dead hare on baby’s gums relieves teething pain? Is it mumbo-jumbo or jumbo-mumbo?

    3 = C This demonstrates the wonders of DNA*

    4 = B This defies logic and whoever came up with the idea saved thousands of lives.

    5 = C Like charlatans, the dragons hunt and ambush in teams and hate to have water poured over their case. Should you visit Indonesia make sure you carry a water pistol and a good supply of water to keep the dragon at bay.

    6 = A Rodents are wired differently to primates. Were the geneticists choices influenced by a cartoon?

    7 = B Not a good thing to spew in polite company.

    The answer sequence ‘BACBCAB’ is a palindrome – the sequence can be read from either end. While DNA recognition sequences vary widely, with lengths between 4 and 8 nucleotides, many of them are palindromic.

    On palindromic sentences, we have: ‘Madam I’m Adam’ (needs a small juxtaposition of a space and the accent.)

    Maybe a word-unit palindrome is more to your taste: ‘Women understand men, few men understand women’

    Or the serenely observational: ‘Fall leaves after leaves fall’

    Perhaps wistful is more fitting: ‘You know I did little for you for little did I know you’

    And finally, I offer: Fog creates doubt, doubt creates fog.

  20. Scott says:

    Yet more spam with no relationship whatsoever to the topic. If you really want to spout random drivel, start your own blog.

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