Tuesday, 2 January 2018

Trust me it's good for you!

On how patients with multiple sclerosis weigh side effect severity and treatment efficacy when making treatment decisions.

Exp Clin Psychopharmacol. 2017 Dec;25(6):479-484. doi: 10.1037/pha0000152.

On how patients with multiple sclerosis weigh side effect severity and treatment efficacy when making treatment decisions.

Jarmolowicz DP, Bruce AS, Glusman M, Lim SL, Lynch S, Thelen J, Catley D, Zieber N, Reed DD, Bruce JM.


Although effective disease-modifying treatments (DMTs) are available for individuals suffering from multiple sclerosis (MS), many patients fail to take their recommended medications. Unlike medications that provide immediate relief from existing symptoms, DMTs decrease the probability of future symptoms (i.e., a probabilistic benefit) while concurrently carrying an appreciable risk of immediate side effects (i.e., a probabilistic cost). Prior research has shown that both the probability of reducing disease progression and the probability of experiencing side effects impact patients' likelihood of taking a hypothetical DMT. The role that side effect severity plays in treatment decisions remains unexplored. The present study examined how probability of medication efficacy and side effect severity impact patients' likelihood of taking hypothetical DMTs. Patients' likelihood of taking a DMT systematically decreased as medication efficacy decreased and side effect severity increased. Because side effect severity appears to impact decision-making processes in unique ways, the present results suggest that providers should present information on severe (which are typically rare) and mild to moderate side effects (which are more common) separately.

Trust is a state of mind, built and sustained by small actions over many encounters, and once you have it solid as the Rock of Gibraltar. This is why the doctor-patient relationship is trickier than your usual run of the mill social encounter. The stakes are also high; future health vs potential harm. In what is essentially an encounter littered with emotive undertones (particularly when it comes to treatment decisions), can you steer decision making process to the mutual satisfaction of both parties?

In this publication, Jarmolowicz et al. found that the likelihood of uptake of treatment in MS reduced as the likelihood of benefiting from the treatment reduced (no surprise there; see Figure 1 below). They also found that there was consistent effect from side effect severity in decision making processes, such that likelihood of risking severe side effects is significantly less than the likelihood of risking moderate and mild side effects. Also called the 'prospect theory' in economics, where there is essentially an over-valuation of losses over gains (see Figure 2 below).

Figure 1: Left graph shows the probabilities of taking medications (y-axis) at each odds against treatment success (x-axis) on questions with mild (open circles), moderate (gray circles), or severe (closed circles). The top right graph shows delay discounting rates (LN[k]) for each side effect severity (different color bars), with error bars showing the 95% confidence interval. The bottom right graph shows the value of A (i.e., fitted parameter showing likelihood of taking medications when they are 100% effective) for each side effect severity (different color bars), with error bars showing the 95% confidence interval. Asterisk indicates statistically significant (p < 0.001) comparisons.

The authors therefore advice that clinicians separate out the discussions on severe vs mild to moderate treatment-related side effects, and to perform a comprehensive assessment of patient motivation and decision making at the beginning. 

The question is whether being aware of the pitfalls in health encounters make us better clinicians, or better patients at the end of the day?

Figure 2: Prospect theory - the value function is steeper for losses than gains indicating that losses outweigh gains.


  1. "better patients"

    Could you please define what does it means to be a "better patient"?

    In your prespective..... :)


    1. There’s no wrote answer to this, patients like doctors gravitate to each other and find an equilibrium which works best for both.

    2. "supply and demand"

      Kind of ,market, commodities, environment

      In the end only one will feel the pain .... :(


  2. I see the argument but to my mind this is trumped by the degree of trust I have in my neurologist. I will bow to his judgement (although he is not one to say - do this regardless and is very responsive to my needs/situation). Your post is appreciated - it makes me realise how (frighteningly) much I DO rely on the trust relationship.

    1. Thanks Cameron. During my internship/house officer year, this was one of the frightening concepts I had to wrap my head around; the trust which patients and families place in you. Health problems unlike anything in life are a good leveller and pretty much everything else stops at the door when you walk into a hospital. My patient list reminds me that I see way too many people every year, and have won some and sadly lost some, but hopefully learnt a lot in the process. The key I’ve learnt to all of this is to keep going.

  3. There is so much truth to what Cameron has posted. MS is an ongoing disease and as such you form a relationship with your Neuro. My Neuro died a year ago and this put his skills and our give and take front and center as I looked for a new doctor. While I do believe the doctor should be an expert in MS, the patient cannot blindly follow. It is the patient's responsibility to understand his/her own presentation of MS and his/her responsibility to follow the doctor's instructions. No treatment will work if not taken as intended.

    I would add one comment to the above study: I started Tysabri very early after diagnosis and while it was a very difficult decision given the risks and so many unknowns, I am stable. What has now become a road block for me is changing therapies as I am JCV+. It is not about the efficacy of the new med which I believe to be strong but the side effects and unknowns.

    As a society, risk is not a topic that is learned or well understood by many.

    Thank you for today's post,


  4. 'The authors therefore advice that clinicians separate out the discussions on severe vs mild to moderate treatment-related side effects, and to perform a comprehensive assessment of patient motivation and decision making at the beginning.'

    I am a rubbish patient, and I live with the consequences.

    'Better patients' have probably already experienced the above.

  5. Not often I add my 10 pennath here but having read the above I find it hard to imagine how someone funded a piece of research into to take the decision making process to document the obvious in an overly complex, somewhat incomprehensible and overtly insulting manner.

    Donald Rumsfeld described this process many years ago in a very simple way which as a rule tends to apply ...

    There are known knowns - These are things we know that we know.
    There are known unknowns - That is to say, there are things that we know we don't know.
    There are also unknown unknowns - There are things we don't know we don't know.

    With MS this 'risk assessment' looks like this :

    - Known, Known - We KNOW we KNOW - MS is progressive - Left alone it WILL get worse
    - Known, Known - DMT's can halt or slow progression down
    - Known, Known - DMT's have side effects - The risk of and effects of these side effects can be assessed in relation to the Known parameters of MS progression

    - Known, Unknown - The form of how MS will get worse and when is unknown
    - Known, Unknown - MS is not a 'recipe' with an expected output, every persons experience is unique we Known the Unknown is the form our progression will take

    Unknown, Unknowns - The future is not set, I might get hit by a bus tomorrow, it's an unknown unknown, whether I'm running across the road to catch it or moving so slowly in a mobility chair or on sticks is an unknown, unknown

    What I do Know that I Know - If I do nothing it WILL get worse so I will pick the one that gives me the highest chance of stopping this nonsense dead in it's tracks as effectively as possible without increased risk of loss of life

    1. When they post stuff like this I imagine they must be bored, drunk or after a reaction.

      DMT's confuse me. Do any of them come 'without increased risk of loss of life'?

    2. Neither bored or drunk (at least anymore after the festive season) but certainly seem to have achieved the latter ;-)

  6. If neurologists were less biased and had no agenda, trust would be easier to build.

    Always pushing the latest dmd's, until a year down the line i.e. pml rates are revised.

    Also their dogmatic refusal and scaremongering about hsct is criminal and cruel.

    I can count at least five neuros who have changed their mind about hsct having previously said the patient faced certain death.

    It's the neurologists who should take a long hard look at the mental impact of their unforgiving behaviour.

  7. This article reminds me of my own daunting decision. In U.S. Slow progression..probably SPMS. On Tysabri, and trustworthy doc is suggesting Ocrevus. Not sure I agree though. Family history of breast cancer. It is so hard to make a decision.


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