Sunday, 10 June 2012

The MS cure, that isn't

A surgeon in Italy has developed an operation to treat MS (multiple sclerosis), based on a biological plausible theory, and he has reported good results after the treatment. As readers know, this is usually enough to get an operation accepted, and it is the only support behind many current operations. Readers should also know that these criteria do not provide proof of effectiveness. In this story though, it is the patients who have pushed for this treatment to be available.
The vascular surgeon involved developed an operation to treat raised venous pressure (named CCSVI: Chronic Cerebrospinal Venous Insufficiency) in patients with MS, based on the theory that increased pressure in the veins leads to blood cells leaking through the blood-brain barrier, which leads to iron deposits in the brain, which leads to something else, which leads to MS (I don’t have much interest in biological theories; they are easy to propose, and the proof is what is important). He reported good results in series of patients with MS treated with a procedure to widen the veins (named the liberation procedure). To his credit, he suggested that better studies be done, with control groups and random allocation. But it was too late, the social network genie was already out of the bottle.

The support amongst the public was quite amazing for an operation with questionable effect and minimal supporting evidence. The facebook page has over 21,000 ‘likes’. Someone has already written a book on the subject, and there is a CCSVI Alliance. The mainstream media and internet sites have joined in (here, here, here). Count the hype words (“groundbreaking”, “revolutionary”, “breakthrough” etc.) and note the references to the medical community’s tardy response to this miracle. (Addit 11 June: I have also been sent this link to an article on the social network phenomenon relating to this - thanks AA, and I also found this one).

So what do we have: a theory of biological plausibility - connected to a procedure to correct the biological cause – uncontrolled and unblinded studies showing promising results – in a condition with widely fluctuating clinical manifestations, therefore allowing the interpretation of post-operative symptoms and signs to be biased by a combination of wishful thinking and subjective criteria. The subjectivity of the outcomes is enhanced by the fact that this operation is meant to work on patients with a recurring-relapsing (fluctuating) form of MS: a condition tailor made for misinterpretation of outcomes.

So how does this procedure fit my template for placebo procedures? There are basically two stages. Stage 1 is when we have early favourable results from a new treatment based on a biologically plausible mechanism. Stage 2 is the lack of support from later, more rigorous studies (usually involving a comparison group, preferably a blinded placebo) and the reporting of previously unexpected harms. In this case, the biological theory behind it does not even have strong support (here, here, and here) and the harms (including death from the treatment) have already been documented. All this before the randomised controlled trials (RCTs) have even been done. I would be very surprised if this treatment proves successful in rigorous randomised trials (trials with weak methodology will show a benefit if the researchers are convinced that it works). But my opinion is not important; such a controversial topic can only be settled by good scientific studies. The RCTs should be done, and if there is not enough evidence to justify an RCT, then the procedure should be stopped.

So is this a fraud (an intentional deception)? My opinion on this, and many other cases like it, is that the doctors involved honestly believe in the theory and the treatment. In fact, it is those very beliefs that can bias their interpretation of the evidence. While this is wrong in the scientific sense (a deviation from the truth), it is not wrong in the moral sense (dishonest or fraudulent).

This whole story gives us a good reason to be sceptical when something comes out of left field (what one commentator called a “Eureka moment”). Next time you see an extraordinary claim like this, remember the words of Carl Sagan:

“Extraordinary claims require extraordinary evidence.”

I am happy to be proven wrong on this one, but at least prove me wrong in the scientific sense, by showing me the evidence from a scientific experiment (a blinded randomised clinical trial). Don’t just say that I am wrong because you want the treatment to work.

For further reading, there is a website devoted to the CCSVI–MS hypothesis that has links to publications and media coverage, but the Wikipedia site has the best coverage of the whole thing. For a good scientific look at the topic, read (renowned skeptic) Steven Novella’s article here, the website devoted to CCSVI from the Multiple Sclerosis Society of Canada, and click here for the most detailed systematic reviews of the published science. It is sobering.

Addit August 2015:
Two studies have shown that CCSVI is not associated with MS (2013 and 2014), the last one accompanied by an editorial that was very negative on the whole theory (here).
Two large RCTs are underway in Canada and Italy, but one smaller sham study (terminated due to lack of recruitment) reported on 19 patients and concluded that the treatment is not effective and may make it worse.

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