Sunday, 3 April 2016

ClinicSpeak & BrainHealth: the therapeutic illusion

Am I a therapeutic illusionist? #ClinicSpeak #BrainHealth #MSResearch #MSBlog

"I am often accused of overhyping what DMTs can do for people with MS, i.e. creating false expectations. A large number of my colleagues have, and  continue to, criticise my early effective treatment strategy and my zero tolerance strategy of treating-2-target of NEDA (no evident disease activity). They claim that if we treated all pwMS like this most will end-up on highly effective treatments when they don't need to be on these treatments and we would also be exposing a proportion of pwMS destined to have benign disease to unacceptable risks associated with treatment. I counter these criticisms with: (1) If most people end up on highly-effective treatments then they probably need to be on these treatments; why would anyone leave their MS active if they had other treatment options? (2) Similarly, benign MS in is rarely benign MS and we can't really make a call on who is going to end up with benign disease. One of my treatment aims to make MS more benign, than benign MS (see previous post on this subject)."

"Critics of my approach would be interesting in reading the perspective piece in last week's NEJM on the therapeutic illusion; the corollary of therapeutic nihilism. According to the therapeutic illusion our efforts to treat MS effectively are being overestimated and are being reinforced by a tendency to look selectively for evidence of impact, i.e. the so called confirmation bias that leads us to seek only evidence that supports what we already 'believe' to be true. I have alway shied from using the term 'believe or belief' and prefer to the terms 'hypothesis or hypothesise'; you can't test beliefs scientifically, whereas you can test hypotheses scientifically and set a go-no-go set of criteria that allows you to reject or accept the hypothesis. The latter is underpinned by the philosophical principles and writings of Karl Popper. My colleagues and I, who are promoting the 'early effective  treatment paradigm' and 'treat-2-target of NEDA (not MEDA)' - one strand of our 'Brain Health: Time is Brain' policy - are testing a series of hypotheses. There is good evidence to support accepting several of these hypotheses and their are ongoing experiments that will allow us to reject or accept others. The real question is 'should we make decisions for our patients and make them wait the necessary 10-15 years for us to answer these questions before adopting these treatment principles' or 'are we willing to accept the risks and undefined benefits of a treatment paradigm that is based on sound scientific principles and support our patient's and allow them to make their own decisions'? With the latter approach at least we would both be succumbing to the therapeutic illusion, or not!"

"I always reference my rheumatology colleagues who are 15-20 years ahead of us in treating rheumatoid arthritis (RA). When the started treating-2-target with zero tolerance, treating early and effectively and flipping the pyramid by using biologics first line, they didn't have the evidence at hand that they would change the natural history of RA. They had early data on surrogate markers of prognosis, i.e. subchondral erosions (small cystic loss of bone under the joint cartilage), that led to hypothesise that they were onto something big. The evidence to support their treatment approach then gradually emerged. The MS equivalent of subchondral erosions is brain atrophy, T1 black holes on MRI and spinal fluid neurofilament levels, i.e. markers of end-organ damage. So when we markedly reduce markers of end-organ damage with the early effective treatment of MS I am confident we are also onto something big. Just as rheumatologists have reduced the need for joint replacements by over 80% with their aggressive treatment approach I am confident we are going to do the same in MS only this time we will be counting walking sticks and wheelchairs, or preferably employment rates or some other more meaningful patient-related outcome."

David Casarett. Perspective: The Science of Choosing Wisely — Overcoming the Therapeutic Illusion. N Engl J Med 2016; 374:1203-1205.


.... In recent years, the United States has seen increasing efforts to reduce inappropriate use of medical treatments and tests. Perhaps the most visible has been the Choosing Wisely campaign, in which medical societies have identified many tests, medications, and treatments that are used inappropriately. The result is recommendations advising against using these interventions or suggesting that they be considered more carefully and discussed with patients......

...... The success of such efforts, however, may be limited by the tendency of human beings to overestimate the effects of their actions.....

...... Psychologists call this phenomenon, which is based on our tendency to infer causality where none exists, the “illusion of control.” In medicine, it may be called the “therapeutic illusion” (a label first applied in 1978 to “the unjustified enthusiasm for treatment on the part of both patients and doctors”)...... 

....... When physicians believe that their actions or tools are more effective than they actually are, the results can be unnecessary and costly care. Therefore, I think that efforts to promote more rational decision making will need to address this illusion directly.......

....... The phenomenon has since been described in widely varied settings. Gamblers, for example, consistently overestimate the control they have over outcomes, both in gambling and in everyday life. Their belief leads them to engage in seemingly bizarre or ritualistic behaviors such as throwing dice in a certain way or wearing specific colors. But the illusion of control is widespread, and its effects may be enhanced when people are placed in positions of authority or subjected to time pressure or competition........

........ Moreover, the therapeutic illusion is reinforced by a tendency to look selectively for evidence of impact — one manifestation of the “confirmation bias” that leads us to seek only evidence that supports what we already believe to be true........

........ Physicians may be particularly susceptible to that bias when caring for a patient with a complex illness. When a patient has multiple medical problems, it’s often possible to find some evidence of improvement after an intervention, particularly if the patient is being intensively monitored.......

........ The illusion of control is deeply ingrained in human psychology in the form of a heuristic, or rule of thumb, that we rely on to interpret events and make decisions. Many heuristics are subconscious and therefore difficult to avoid or eradicate, but we can ameliorate their effects by using countervailing, conscious heuristics. Indeed, physicians already use this strategy to improve diagnostic decisions. For instance, we tend to ignore the pretest probability of an illness when making a diagnosis, which can cause us to overdiagnose rare conditions and under diagnose common ones; medical students are therefore taught the rule “When you hear hoofbeats, look for horses, not zebras.”.....


  1. Are there any lessons to learn from your endocrinologist colleagues? I saw and article yesterday about the rise in diabetes cases and the huge number of amputations. One diabetes doctor used the term 'time is tissue'.

  2. What about SPMS? Early effective treatment strategy prevents conversion to SPMS?

    1. It will take time to know this, the 10 year data of alemtuzumab was about 5% but there is no comparitor

    2. It will be very usefull to know baseline data (average EDSS, desease duration, age, past treatments) of pxMS analised after 10 years of Alemtuxumab treatment, to have better view on DMD treatment effect.

  3. I firmly believe in this line of thinking and am fortunate to have been treated by a Neurologist who is labeled aggressive. I live in the US and more and more it is insurance driving this issue. I have been on Tysabri for 10 yrs and my MS seems to have been stopped in its tracks. Now to tackle all of the other issues that come with aging!

    These conversations need to be seen in the light of Risk vs Reward. Often times very hard for the patient to understand and not all doctors are up to date.

  4. DMT is problematical term.
    Do they work..???
    If they stop spms then what you have
    is a treatment that is a cure.
    Lemtrada may do it...but all the others
    from BetaSeron in 1993 to today don't stop spms
    or brain atrophy. Eating vegetables..getting sleep..
    meditation..and DMT's are great ideas but if they
    don't stop onset of SPMS...they don't work.
    And the proof is all the people rolling the HSTC dice
    for $50-$150,000

    1. This is anecdote where is the data?
      Because many of those people paying dont go into a data base. For non-myeloablative there is a failure rate is that because it fails or because the procedure was done too late. I suspect abit of both

  5. I agree with all the arguments. It is very complicated to change the vision "of the world" the medical community. I bring up the subject of neurofilament and neuroprotection and received a curt reply "dr. boas only will become clinical practice when more studies confirming the".
    I felt like the time to ask "what world she lives? Or where historical time? Early twentieth century?"
    ...If Charcot was alive would have great disappointment with the neurological medical community...

  6. "Why would anyone leave their MS active if they had other treatment options?"

    Lazy neurologists :-)?


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