This is Marie--what follows is opinion and naturally not meant to be taken as medical advice but rather meant as food for thought and discussion with your own personal doc.
We often hear that treating MS as soon as possible with drugs that suppress immune system function is the only way to handle MS. This is in spite of the fact there is a large body of evidence that suggests MS is primarily a degenerative disease with inflammation a secondary event as the body tries to heal the damage. If this point of view is correct, suppressing immune system function will only mask symptoms without making much impact on actual losses over the long term.
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There are a lot of ways to slice and dice raw data and proponents of the autoimmune theory produce a huge amount of research, whether directly supported by pharma or not. Unfortunately there is gowing evidence of data manipulation in our evidence base.
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Here's an example of a recent abstract that may lead readers to an unjustified conclusion:
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This is a study an Italian neurologist conducted using data from 1178 people followed in 3 clinics over 10 years. They additionally evaluated patients who converted to progressive status so they could devise an evaulation tool that predicts which MS patients have the highest risk of progressive disease. They also compared progressive status in treated and untreated people.
Of these 1178 people, 478 decided not to take any DMT (disease modifying therapy) and 700 had taken one of the several available drugs.
Of those that took drugs, 606 were on either an interferon or glatiramer acetate (GA) for 10 years. The author decided to focus on this group of treated people rather than the smaller groups that took natalizumab, mitoxantrone, or fingolimod. When they compared the untreated people to the GA or interferon treated people they found that after 10 years 97% of treated people were not yet progressive whereas only 79.9% of the untreated people remained free of progression.
They also showed that their evaluation tool predicted who was at high risk of progression and they asserted that drugs reduced progression for both high and low risk groups. Their tool was an especially interesting part of this research and it may make it possible to tell patients in the first year how progressed they might expect to be down the road.
Sounds really great doesn't it? Comparing treated to untreated people that is a difference of 17.1% in favor of treatment (79.9% compared to 97%) Additionally according to the authors treatment helps everyone whether at high or low risk of progression.
That is a substantial benefit. It sort of says that 1 in 5 untreated people will fall off the disability cliff within 10 years but nearly all treated patients are still OK; that's a big reason to choose treatment.
(remember relative numbers vs absolute data? Note on absolute data) .
But treatment guidelines for MS drugs say that doctors should prescribe GA and interferon initially because of their strong safety profile. If patients progress and do poorly on tier 1 drugs, then guidelines suggest a switch to a tier 2 drug is warranted in spite of their greater risk profile. Remember that the authors excluded the people on second tier drugs like mitoxantrone, natalizumab or fingolimod; assuming these patients were treated according to guidelines the majority should have started with an interferon or GA then switched when they progressed.
So if you take those people who shifted to tier 2 drugs and assume they all switched due to progression not controlled by tier 1 drugs, this substantially increases the number of treated people who progressed while on treatment. It changes the calculation of treated people who remain stable from 97% to 83%.
The math looks like this:
1178 patients total followed 10 years in clinic
478 untreated with 382 still not progressive (79.9%)
606 treated with first tier drugs 585 of which are still not progressive (97%)
BUT 94 of total number of treated patients actually switched to second tier drugs so....
700 patients were treated with any drug (including second tier drugs) and 585 of were not progressive (83%)
After adding in the tier 2 people, now the difference between the treated and untreated people can be expressed as a relative difference of 3.1% (79.9% compared to 83%). That is quite different from 17.1 % treatment advantage prominentlly touted up front in the abstract.
The problem with my re-interpretation is that I add the people who took tier 2 drugs and call them "progressives" attributed to the treated group, which may not apply in individual cases. In this study the term "progressive" was highly defined to mean loss of 1 point on the EDSS sustained over a year. I don't know how many of those who switched to the second tier drugs met that criteria. My assumption that all of them did is a worst-case guess; some may have switched without sustaining an EDSS loss over a full year.
In any case, the people taking tier 2 drugs were doing so because for some reason their MS was worse and the decision was made that a risker drug was best. It's odd that such patients were left out of the calculation because it means that the only-tier-1 group that was included is not representative of general MS populations; by definition this is a group of MS patients with less aggressive disease not yet qualifying for tier 2.
Aside from analysis that excludes people whose data should be pertinent, this study was unblinded, so every doctor evaluating a patient knew if the patient was taking a DMT or not. This is likely to have influenced their interpretation of patient function the same way "placebo effects" confound other studies.
In addition there are actual placebo effects in play here as well: since the only group open to placebo effects was the treated group, they are likely to have a better outcome simply by virtue of the fact they are taking a drug they are told is effective and they presumably believe it.
Also, the groups are not age matched and are of very different size. Since progression seems to be a function of age that could make a big difference. Another problem along thse lines is that is it not randomized, so the patients that self selected to be in the "no-treatment" group may have done so for reasons that would impact MS progression.
But in spite of these issues, this study is internally consistent, meaning that the authors did define what they were looking for and it is good science as it is laid out. They stated up front that progression was defined as sustained EDSS loss over one year and that they were going to exclude patients who were on second tier drugs. Narrowly defining your paramters makes a tighter study so you can know that you are evaluating what you want to. You can say that there is a 17.1% advantage to treatment and be making a valid statement....
...as long as you realize that this exists only in the narrowly defined virtual academic world and not in the real world where real patients live with MS.
...as long as you know that is not what the average MS person in the average clinic can expect when they sign up for a first tier drug because 1 in 7 (94/700) will need a second tier drug.
...as long as you imagine the placebo effect often thought to be around 30% somehow didn't boost the treatment effect in this study.
How a study is designed determines its outcome. How it is presented even in the abstract makes a difference to how it is perceived. Science is not necessarily objective. But it's not really OK to find a way leave out the people who progressed and needed stronger more risky drugs then present the resulting number as if it demonstrates a big treatment advantage in the real world.
That'd be like Zamboni doing a study on CCSVI and excluding all the patients who had to switch to any new or different MS drug after angioplasty. Does anyone think the neurology community would be OK with that? They need to see it in their own work too.
I started this essay asking why there is such an overwhelming and dogmatic belief that the DMTs are making a huge difference to people with MS when there is ample evidence that progression is only modestly reduced and many credible authors are saying MS is primarily degenerative with inflammation a secondary event. The sheer volume of studies like this is why; you can only read so many peer reviewed published studies that say these things work awesomely well before you simply assume that is right.
Pharmageddon by Dr David Healy (p 259) a psychiatrist and critic of pharmaceutical manipulation of science to advance marketing goals:
"A medicopharmaceutical complex has triumphed; everyone seemingly accepts that it would be irrational to do anything but act in accordance with the "evidence." Any sustained attempt to critique current trends is now likely to be dismissed as not evidence based or as an advocacy of postmodernism that denies the reality of disease or scientific progress..."
I talk about this in my book too giving examples of bias. Do you have your copy yet? If not please order yours at http://ccsvibook.com or on Amazon (they have Pharmageddon too) And if you do have a copy tell people trying to understand CCSVI about it. Books stay in print when people order them... thanks! Marie