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Subjective Improvement vs Objective Improvement


ResearchBlogging.org

Yesterday’s New England Journal of Medicine has a study well described by its title – Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma. The details of the paper will be covered in a later post. What I am going to focus on here is the editorial about this paper.

Between January 2007 and December 2008, we conducted a randomized, double-blind, crossover pilot study with the use of a block design to determine the short-term responses to an inhaled bronchodilator and placebo treatments in patients with stable asthma.[1]

First, the surprising result is the subjective response of patients to the various treatments. If we asked them, they felt the same with sham acupuncture, placebo, and with albuterol. Below is the figure of the subjective improvement by intervention.


Click on the image to make it larger.

This is very interesting. This raises a lot of questions. Especially when we look at the measurement of objective improvement.

The most important word, in the description of the participants, appears to be stable.

Would the outcome be at all similar for patients who have significant limitations due to their asthma?

Daniel Moerman, PhD suggests that the objective improvement is not important. The subjective improvement is much more important. Is he right?

Although albuterol improved FEV1 by a factor of 3, as compared with the other three interventions, patients reported no differences in improvement of asthma symptoms. They all felt better, so from the patients’ perspective all three interventions, save simply waiting, worked.[2]

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 FEV 1 . 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?[2]

When do we start to differentiate between a desire for subjective improvement in stable patients and a desire for objective improvement in less stable patients?

Does subjective improvement lead to similar survival?

Would we make the same suggestion about psychiatric treatment?

Would we make the same suggestion about blood pressure treatment?

Would we make the same suggestion about dialysis treatment?

Would we make the same suggestion about heart failure treatment?

Would we make the same suggestion about diabetes treatment?

Would we make the same suggestion for patients who have significant limitations due to their asthma?

Don’t worry about your bluish complexion. Cyanosis is just one of those objective criteria used by doctors. Your subjective impression is what matters. Relax and enjoy the experience, but try to stay away from the light.

When do we stop being impressed with our ability to deceive ourselves?

Do we need to control for all meaning in order to show that a treatment is specifically effective? Maybe it is sufficient simply to show that a treatment yields significant improvement for the patients, has reasonable cost, and has no negative effects over the short or long term. This is, after all, the first tenet of medicine: “Do no harm.”[2]

The third caveat listed is the one that concerns me.

What about this study suggests that there are no negative effects over the short or long term?

When do we no longer receive a benefit from placebo treatment of stable illness and need to add some demonstrably efficacious medicine to attempt to prevent disability or death?

If the patient refuses to use anything other than the placebo, because I just know it will work, when does that faith in the placebo lead to a bad outcome?

Even more surprising than the subjective improvement with placebos may be the complete lack of objective improvement with placebos.

Is the subjective improvement just a delusion?

Footnotes:

[1] Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma
Michael E. Wechsler, M.D., John M. Kelley, Ph.D., Ingrid O.E. Boyd, M.P.H., Stefanie Dutile, B.S., Gautham Marigowda, M.B., Irving Kirsch, Ph.D., Elliot Israel, M.D., and Ted J. Kaptchuk
N Engl J Med 2011; 365:119-126 July 14, 2011
DOI: 10.1056/NEJMoa1103319
No PubMed listing, yet.

Preview from NEJM

[2] Meaningful Placebos — Controlling the Uncontrollable
Moerman, D.
N Engl J Med 2011; 365:171-172 July 14, 2011
DOI: 10.1056/NEJMe1104010
No PubMed listing, yet.

Preview from NEJM

Wechsler, M., Kelley, J., Boyd, I., Dutile, S., Marigowda, G., Kirsch, I., Israel, E., & Kaptchuk, T. (2011). Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma New England Journal of Medicine, 365 (2), 119-126 DOI: 10.1056/NEJMoa1103319

Moerman, D. (2011). Meaningful Placebos — Controlling the Uncontrollable New England Journal of Medicine, 365 (2), 171-172 DOI: 10.1056/NEJMe1104010

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Comments

  1. The authors included the following bit in their discussion, which I found interesting (emphasis mine):

    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… 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.

  2. Hmmm, I haven’t read the article and editorial in question, but from your summary, it sounds like the editorial went a bit too far. I agree with what he seems to say, which is that too many trials focus on surrogate markers of patient improvement and not actual outcomes. Here they attempted to use the difference between FEV1 and subjective experiences as support for the notion that you can improve someone’s numbers without actually making them better.

    It’s the same theme that has been cropping up in the literature recently in regards to cholesterol control. Knowing that high cholesterol is a risk factor for adverse vascular events, drugs were developed to lower patients’ LDL and raise their HDL, with the assumption that these improvements in what we could measure would improve patients’ lives. After treating patients like this for several years, however, data is starting to emerge demonstrating that while the cholesterol levels of the patients on these medications were indeed improving, overall morbidity and mortality stayed the same. Whoops…

    So from the sound of it, while this study didn’t want to fall into the same trap and looked at more than just FEV1 values, it made a mistake of equal magnitude by still focusing on the wrong outcome. People’s subjective accounts of their symptoms and the effects a disease has on them can differ wildly from what is actually occurring (Thanks for that comment Christopher, the authors seem to recognize that, leaving me confused about these two conflicting ideas in the same paper). How often do we see older folks with CHF or COPD huffing away at 30 breaths per minute and unable to walk more than a couple feet who still say, “I’m fine.” A more useful measure of the various treatments’ effects in this study would have been a more objective, such as exercise tolerance, number of ED visits, or number of times they had to resort to “rescue” inhaler use.

    • Just to clarify my comment above; I think the study actually shows an interesting effect, and although I may have sounded critical of its design, what I actually didn’t like was the editorialist’s interpretation. As Christopher quoted, the study authors seem to get what their data showed, it’s just Dr. Moerman that harped on subjective feelings like they were as useful as objective outcomes.

  3. Certainly interesting to read. It makes me wonder what onset of sysmptoms was, severity of initial presentation etc, but “sham acupuncture?”
    Is that purposely misapplied acupuncture? I know your feelings about it and the studies, but what does sham acupuncture mean?

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