Friday, 29 July 2011

CCSVI: Zamboni should have declared his conflicts of interest

In response to a previous comment and my response.

"I only realise now that most MS'ers are not aware of some very important background information in relation to CCSVI."

"The worrying and most upsetting thing about the whole CCSVI saga is the fact that Zamboni had, and still has, massive conflicts of interest. He has patents in relation to CCSVI and received money from a company that sells the equipment for diagnosing CCSVI."

Read about it in the National Post and The Globe and Mail.

"If he had declared these conflicts of interest early on I suspect we, the scientific community and MS'ers, would have been much more critical of his claims."

"May be the unnecessary deaths due CCSVI procedures and the unnecessary diversion of valuable research funds into CCSVI research could have been avoided ."

"The moral of the story; transparency, transparency, transparency."

35 comments:

  1. I don't think the answer is neccesarily transparency. A drug company could pay you £500k consultancy fees to help develop / promote a drug. Just because you declare this (COI) doesn't make it (i) right or (ii) provide me with any information as to whether you have manipulated the data etc. I would still like to see a distinction between (i) public servants (doctors, police etc) and (ii) commercial companies. I don't think it right that I am paying tax which pays for a consultant (any specialism) and they are also receiving payments from commercial companies to do work. How do I know that the consultant isn't undertaking the commercial work in the time he or she is being paid by the NHS / police force etc. I like to think that those in the medical profession in particular are primarily interested in the welfare of their patients - taking money from commercial companies really muddie this ideal. I would argue that if a medic wants to earn big bucks then they should leave the NHS and join a big pharma company. I wouldn't be happy if the Chief Constable for my area was also taking money from a company who sell burglar alarms etc. I'm guessing you will say that this is how the system works. My objections wouldn't be a strong if the treatments coming out of the system got people better. I'd rather have a system where consultants were paid at a level where they didn't have to make up any perceived shortfall by supplementing their income from commerical companies (often many companies).

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  2. Quote from the NP Artical:
    Dr. Zamboni, however, said it is “ridiculous” to suggest his patent applications and work with Esaote S.p.A., the ultrasound manufacturer, represent anything like the conflicts of researchers who receive money from drug companies.

    Esaote has merely provided equipment to his lab and funded professional training, and he has no plans to commercialize the inventions described in the patents, he said in an emailed response to questions.

    In fact, one prominent Italian neurologist who is highly skeptical of Dr. Zamboni’s ideas dismissed as insignificant any commercial interests the surgeon might have. What is important is completing a slew of studies now under way that should answer whether the theories hold water or not, said Dr. Giancarlo Comi of Milan’s San Raffaèle institute.

    Dr David Baker said at the MS Research day that taking out patents on your work is a regular part of developing a new treatment.

    Fact is that his findings have been reproduced elsewhere and that catheter venograpy shows the reflux of blood in these veins very clearly.

    If your argument is only that he should have been more transparent, then this is probably true. To equate this to mean that all of his work is a fabrication only to make money, and that there is no worth to the work being done on CCSVI, is frankly absurd.

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  3. Prof G, what about your conflicts? Cladribine has been banned from being used as a treatment because of it's side effects yet you still push it.

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  4. "If he had declared these conflicts of interest early on I suspect we, the scientific community... would have been much more critical of his claims."
    Is this really possible??

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  5. Re: above posts.

    The bottom line is if you have a conflict of interest your declare it. It is then up to reader and the community to decide how to interpret the findings. Zamboni's mistake is that he did not declare his conflicts of interest. Did he have something to hide?

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  6. The real conflict of interest is that big pharma are doing very well e.g. Biogen's profits, the MS research community is doing very well e.g. consultancy fees and conferences in exotic places like Hawaii, yet the poor MS sufferer is given no chance to get well again. The whole system stinks - given that a cure would stop any more profiteering for big pharma and and X,000 researchers around the world would be looking for a new career, no wonder any breakthrough is alwways 10 years away.

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  7. Re "The real conflict of interest..."

    That interpretation is fine; at least you able to make that call because the conflicts are declared. Zamboni's made the mistake of not declaring his conflicts of interest. Did he have something to hide?

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  8. 'Zamboni's mistake is that he did not declare his conflicts of interest. Did he have something to hide? '

    For an intelligent man, I think you do write a lot of 'stinky cheese' on this subject, but at least you provide a forum for discussion!

    Another quote from NP:
    "Mariangela Dellepiane, a spokeswoman for Esaote, said the company has worked with Dr. Zamboni and his centre for vascular diseases at the University of Ferrara for years, and developed MyLab Vinco according to his research. The firm pays Dr. Zamboni’s centre to train its customers on use of the system, but provides no other payment linked to its sales, she said in an emailed response to questions."

    And from The G&M:

    Dr. Zamboni: “They gave us just equipment and technical assistance, nothing more. I am really completely independent from Esaote.”

    And:
    “If something is real, you should be able to find it using different techniques,” said Dr. Traboulsee"

    Venography anyone?

    You really have blown this story up out of all proportion, and not explained how your conclusion about CCSVI in general can be drawn from the articles.

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  9. People who live in glass houses..

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  10. ‘Bad Science’ author Ben Goldacre believes the conflict of interest is unacceptable when drug companies conduct trials on their own drugs.

    http://www.bmj.com/content/339/bmj.b4949

    “A systematic review found 30 studies investigating whether industry funding is associated with outcomes that favour the funder: studies sponsored by drug companies were more than four times as likely to have outcomes favouring the funder, compared with studies with other sponsors.”

    How many MS drugs were trailed by completely independent bodies that were not sponsored by the manufacturers?

    How many were not?

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  11. Re: "“A systematic review found 30 studies investigating ...”

    Thanks for quoting this; I have previously posted on the issue see: http://multiple-sclerosis-research.blogspot.com/2011/06/are-pharma-sponsored-trials-biased.html

    This is exactly the point I am trying to make; when there is a conflict of interest it introduces a bias and results in a positive skew in the results. I suspect this is what happened with Zamboni, which may explain the slew of negative CCSVI studies that have subsequently followed his original publication. It is a pity he didn't declare his conflicts of interest; the MS community's response to the original publication would have certainly been more muted.

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  12. EMD Serono and its affiliates have agreed to pay $44.3m (£27.2m; €31.1m) to resolve allegations relating to the marketing of its multiple sclerosis drug Rebif (interferon beta-1a), the US Department of Justice announced on 4 May (2011). The department said that the settlement resolved allegations brought under the False Claims Act that Serono paid healthcare providers to promote or prescribe the drug from the time of its launch in January 2002 until December 2009. (BMJ 2011;342:d2922)

    $44 million, now that's a lot of money. I couldn't find this story highlighted on this blog. I would have thought it should have been.

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  13. Re: "EMD Serono and its affiliates have agreed to pay $44.3m (£27.2m; €31.1m).."

    I agree this is outrageous and EMD Serono have been punished accordingly. But I must be missing something; what has this to do with CCSVI and the cause of MS? We really need keep these two debates separate. What we should focus on in relation to this particular post is the evidence base for CCSVI as a cause of MS and whether of not treating the condition helps MS'ers or cures then of the condition. The scientific framework on which we should be holding this debate is around Bradford-Hill's criteria for causation.

    Please see my previous post on this issue: http://multiple-sclerosis-research.blogspot.com/2011/04/ccsvi-time-for-sir-bradford-hills.html

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  14. Prof G, what is it about this I'm missing:

    'Esaote has merely provided equipment to his lab and funded professional training, and he has no plans to commercialize the inventions described in the patents, he said in an emailed response to questions.’

    It seems he made an error in not saying this at the time, but it is hardly an earth shattering scandal. It escapes me to understand how it is as seismic as you seem to think it is, especially compared to the Serono story just posted. It seems like your clutching at straws to me.

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  15. 'But I must be missing something; what has this to do with CCSVI and the cause of MS?'

    This thread is about conflict of interest too.

    'CCSVI: Zamboni should have declared his conflicts of interest'

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  16. Re: "$44 million, now that's a lot of money. I couldn't find this story highlighted on this blog. I would have thought it should have been."

    This specific issue was covered with an exchange on this blog on the 11th May 2011 and was followed by a post in relation to Pharma's influence and a survey was then done on the issue.

    Please see the following posts:

    http://multiple-sclerosis-research.blogspot.com/2011/05/hot-topics-in-ms.html

    http://multiple-sclerosis-research.blogspot.com/2011/06/are-pharma-sponsored-trials-biased.html

    http://multiple-sclerosis-research.blogspot.com/2011/07/survey-results-on-influence-of-pharma.html

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  17. Re: "It seems like your clutching at straws to me."

    Not at all; 2 people have died and may be more.

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  18. The question I asked was:

    Prof G, what is it about this I'm missing:

    'Esaote has merely provided equipment to his lab and funded professional training, and he has no plans to commercialize the inventions described in the patents, he said in an emailed response to questions.’

    It seems he made an error in not saying this at the time, but it is hardly an earth shattering scandal. It escapes me to understand how it is as seismic as you seem to think it is.

    I would like to understand this.

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  19. What a lot of chat today!

    'What we should focus on in relation to this particular post is the evidence base for CCSVI as a cause of MS and whether or not treating the condition helps MS'ers or cures them of the condition.'

    Good sentiment, but surely most of these questions cannot be answered at this time. You know that many trials are being done, and that the Canadian health service and NICE are both looking into CCSVI. I think this is a good way to proceed, but you seem to be against this work, calling it “the unnecessary diversion of valuable research funds into CCSVI”. As far as whether venoplasty helps MS’ers; it has helped me any many others a great deal, but you just dismiss this sort of experience as ‘some anecdotal reporting’.

    I don’t see either how this smear story is getting us closer to the answers. So much has happened since Zamboni’s original findings. As I mentioned at the top, much of his findings have been reproduced elsewhere and that catheter venography shows the reflux of blood in the jugular and azygos veins very clearly, independent of the use of doppler ultrasound. I’m sure you could see the work being done at first hand if you choose to.

    If I had known before I had venoplasty treatment that Zamboni owned a patent to a piece of equipment he had developed, and that the company who made it provided equipment to his lab, I wouldn’t have found it outrageous or even mildly troubling.

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  20. I think everything about CCSVI probably irritates and upsets Prog G, as CCSVI does not fit known facts about MS.

    I don't see how this patents & equipment thing is such a major conflict of interest. But there are other conflicts of interest as the National Post article says
    "... one prominent Italian neurologist who is highly skeptical of Dr. Zamboni’s ideas dismissed as insignificant any commercial interests the surgeon might have ... (his wife's MS) ... gives Dr. Zamboni a strong personal motivation ... (that is) more than any economic motivation.”

    What strikes me as strange is that other studies are not getting anything like what Dr Zamboni reported, eg the percentage of MS'ers with blockages.

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  21. The reason the Serano case is relevant because it is the same MS profit centers who were guilty of taking bribes for prescribing overpriced-deadly-drugs-that-don't-work, who made the most outrageous warnings about CCSVI. After 15-20,000 cases worldwide and very few complications, (and 3 somewhat related deaths), the "hoax" claims are just that.
    It is past time for these naysayers to quit boycotting CCSVI research and help the interventionalists assess patients before and after treatment as Mike Dake just called for. Only then will we have the answers we need.

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  22. On the other hand, if patients are aware of the risks, why not let them get venoplasty for the symptomatic improvement?
    In the process data can be collected on how many patients benefit, how much they improve, how long the effect lasts, etc

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  23. Hi Roshni, good to read your comments.

    I think even Buffalo’s initial finding of 62% CCSVI positive is still significant. This figure was an average of all types of MS’ers: 38% of those with an initial demyelinating event had CCSVI, rising to 80% of progressive MS patients. They concluded that their results “point against CCSVI having a primary causative role in the development of MS”. On the other hand it also shows CCSVI is definitely associated with MS. MS is complicated – who knew?

    In the last six months or so there has been a standardising of diagnostic testing in many of the centres performing CCSVI diagnosis so that a ‘like for like’ comparison can be made more easily. I know that the clinic in Scotland that is performing venoplasty for CCSVI is collecting the sort of data you mention. I got my 3 month questionnaire yesterday. They also do a 6 month follow up with a repeat MRI scan, repeat tests of walking speed, coordination and the PASAT cognitive test.

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  24. I'd rather the funds being given for CCSVI were now allocated for bone marrow stem cell trials. The former is a bluff, while the latter holds scientific potential to actually treat MS.

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  25. I am incredulous at a possible disbelief that dysfunctional veins that drain the brain and spinal cord (the nervous system/mylein can be dismissed as irrelevant. That reflux of old metabolically processed blood that must go back to the heart for re-oxygenation is not alarming. Drs like Dr. G are abound and make a great deal of money from the sick and crippled. How else can ZAMBONI, et al. can perfect diagnosis and treatment of these newly discovered defective valves veins. I personally am witnessing business as usual in the medical arena. THERE ARE TRUE DOCTORS WITH A PURPOSE, AND THEN THERE ARE DOCTORS LIKE DR. G.

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  26. I suggest people who post comments should try to stick to the facts. To use Ben Goldacre's example, as a non-expert it appears that CCSVI is no better than snake oil. I agree the money currently being spent on treating and investigating CCSVI would be better spent on finding a treatment for progressive MS.

    Prof. G please keep looking.

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  27. 'as a non-expert it appears that CCSVI is no better than snake oil'.

    I fail to see any facts here.

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  28. NO CURE EVER FOR MS - B ECAUSE THE CONGENITAL VEINS BRAIN AND SPINAL CORD VEINS- WILL BE HERE FOR AS LONG AS WE ARE - JUST TRY TO FIND WAYS TO MAKE THEM WORK.

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  29. DOC AND OTHERS - WHAT ARE YOU SAYING - BLOCKED VEINS ARE GOOD FOR US?? HOW DUMB ARE WE???

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  30. Hopefully the NICE review will settle these arguments; that is assuming the MS community is willing to accept their independent status and methodology.

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  31. This post is false. Zamboni has always declared his conflicts of interest. I have heard him speak in person, you obviously have not! his patents and associations have been publicized widely. Begs the question about your conflicts of interest!

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  32. False premise. Zamboni has always disclosed his conflicts. The rest is just your usual bustling comments, which begs the question, Where do you disclose?

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  33. ALWAYS DISCLOSED

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647682/

    J Neurol Neurosurg Psychiatry. 2009 April; 80(4): 392–399.

    conflicts of interest = NONE

    WHERE DO YOU DISCLOSE?

    Look at the home page and look for disclosures. Look on relevant posts and look for CoI. Look at the papers we write.

    YOU HAVE NOT HEARD HIM

    He has spoken at events that Team G have attended.

    This argument is now irrelevant the reality will be out soon enough as the trials roll out.

    There is already a weight of evidence that the original descriptions have not be borne out by others, not all the studies can be put down to flawed methodology.

    Will venoplasty have benefit? I will wait and see with an open mind. If it does great, if it doesn't then time to move on.

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  34. Some Zamboni patents, were any of these relevant to the paper above?

    SYSTEM FOR DETECTING EXTRA CRANIAL VENOUS FLOW ANOMALIES August 2009

    A DILATION CATHETER...March 2008

    A DEVICE FOR TREATING VALVULAR MALFORMATIONS IN PERIPHERAL VENOUS VESSELS, SUCH AS INTERNAL JUGULAR VEINS AND KIT 2009

    STENT, FOR EXAMPLE FOR TREATING JUGULAR VEINS, AND CORRESPONDING DELIVERY..SEPT 2008

    System for diagnosing multiple sclerosis.....Feb 2008

    NOW HOW ABOUT

    PATENT NUMBER: WO2012123785
    ZAMBONI PAOLO [IT]; GEMMATI DONATO

    GENE POLYMORPHISMS IN MULTIPLE SCLEROSIS.
    A method of diagnosis or prognosis of multiple sclerosis development, comprising the step of measuring in a sample of nucleic acid for the presence of at least one polymorphism in a gene selected from the group of consisting of ferroportin (FPN1) gene, transferrin (TF) gene, hepcidin (HEPC) gene, coagulation factor XIII (FXIII) gene, metalloproteinase-12 (MMP12) gene and haemocromatosis (HFE) gene.


    NOW LOOK AT Gemmati D, Zeri G, Orioli E, De Gaetano FE, Salvi F, Bartolomei I, D 8217 Alfonso S, Dall 8217 Osso C, Leone MA, Singh AV, Asselta R, Zamboni P.
    Polymorphisms in the genes coding for iron binding and transporting proteins are associated with disability, severity, and early progression in multiple
    sclerosis

    BMC Medical Genetics 2012, 13:70 doi:10.1186/1471-2350-13-70

    Competing interests Statement:
    The authors declare that they have no competing interests.

    Could they make money from a diagnostic test?

    Yes-- Zamboni always discloses his conflicts.........NOT

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  35. For your information WO2012123785 date― 2012-sept-20 filed at least a year ago as they do not become visible for a year. Final acceptence of paper July 2012 I guess they knew about the patent and decided to say nothing...again.

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