article "MS drug trial a fiasco"

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Postby patientx » Sun Jun 06, 2010 11:55 am

cheerleader wrote:I didn't make up the prices should be zero, patient. It's in the report. According to the end-point of the scheme, prices are set based on efficacy. The real problem is that the patients on drugs did worse than controls. That's mine and Jeff's concern, as I look at a fridge full o' copaxone.
cheer


Cheer,

I didn't suggest (or mean to suggest) that you made anything up. But, I think people should not rush to judgment, particularly to the conclusion that the CRABS do nothing, based on these reports.

From my reading of these studies, it seems the NHS made a determination in 2002 that is was not cost-effective for them to pay for CRABs for MS patients. They agreed to pay based on the agreement that follow-up studies would be done to determine how much they should pay. Fair enough. But, the CRAB maufacturers only ever advertised a reduction in relapse rates. Yes, the 30% number is sad, but I don't see where they over-stated the efficacy of these drugs.

Now, the first studies are coming out that the NHS did not get its money's worth. I don't find this particularly surprising - the sad reality is that the CRABS don't stop of cure MS. But they made his determination based on what should be predicted (using some sort of mathematical model) compared to what was observed. Is this really the best way to determine efficacy?

Yes, I saw the part that patients on drugs did worse than controls. But I didn't see any elaboration of this. And considering the implications, I find the lack or elaboration remarkable. Why is everyone so willing to accept this at face value?

Look, the CRABS have been shown to reduce relapse rates. Even George Ebers admits this:
Thus the only outcome measure that remained was relapse frequency—and this was unambiguously reduced in patients undergoing treatment in the risk sharing scheme.

And for many people with MS, reducing the number of relapses, which can often leave lasting deficits, is reason enough to take a DMD.
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Postby cheerleader » Sun Jun 06, 2010 12:01 pm

patient...please go back one page and read the research I linked---it's all in there. The references section cite the specific papers on drug efficacy. Even Dr. Compston, the head neurologist, has said this scheme was a disappointment in his commentary.

It is not an elaboration...these are commentaries based on research. Look at each paper, at the bottom of the commentary is a link to the specific research cited. All the facts and figures are listed there. (I was happy to see copaxone fared the best out of all the CRABS for the 15 years it was studied.)
HTH,
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby patientx » Sun Jun 06, 2010 12:05 pm

cheerleader wrote:patient...please go back one page and read the research I linked---it's all in there. The references section cite the specific papers on drug efficacy. Even Dr. Compston, the head neurologist, has said this scheme was a disappointment in his commentary.

It is not an elaboration...these are commentaries based on research. Look at each paper, at the bottom of the commentary is a link to the specific research cited. All the facts and figures are listed there. (I was happy to see copaxone fared the best out of all the CRABS for the 15 years it was studied.)
HTH,
cheer


You have linked a lot of stuff. Maybe you could be a little more specific.
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Postby cheerleader » Sun Jun 06, 2010 12:26 pm

patientx wrote:
You have linked a lot of stuff. Maybe you could be a little more specific.


yeah, sorry.
Here ya go, just scroll down to the bottom of the analysis and check out the "reference" section. It has all the papers-
http://www.bmj.com/cgi/content/full/340/jun03_1/c1672

each BMJ analysis has references at the end with facts and figures.
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby jackiejay » Sun Jun 06, 2010 12:28 pm

I believe I have read that the DMD's were originally to be used short term.....that is when they would be of most benefit. ...but now it seems that it just keeps being prescribed because they have no other substitutes......the doctors don't seem to care about detrimental long term use...probably because no one seems to know the answer to that either or if they do know they feel they should just keep prescribing.....you still leave with your little prescription note....the whole thing is a crap shoot....pardon the pun.
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Postby Trish317 » Sun Jun 06, 2010 12:54 pm

jackiejay wrote:I believe I have read that the DMD's were originally to be used short term.....that is when they would be of most benefit. ...but now it seems that it just keeps being prescribed because they have no other substitutes......the doctors don't seem to care about detrimental long term use...probably because no one seems to know the answer to that either or if they do know they feel they should just keep prescribing.....you still leave with your little prescription note....the whole thing is a crap shoot....pardon the pun.


Doctors are also prescribing these drugs for progressive forms of MS when they know that they aren't actually going to work. My darling man shot himself up with Betaseron for over a year until he finally made the decision to stop because he knew it wasn't helping his primary progressive. It's highly possible that it might have made him worse.
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Postby jackiejay » Sun Jun 06, 2010 1:01 pm

I see in Dr. Simka's letter on another thread that he also recommends continuing neurologic medication.....
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Postby Trish317 » Sun Jun 06, 2010 1:08 pm

jackiejay wrote:I see in Dr. Simka's letter on another thread that he also recommends continuing neurologic medication.....


I completely understand why Dr. Zamboni, Dr. Zivadinov, and Dr. Simka would say that people should continue with these drugs. But, in light of this recent information, I've wondered what their thoughts are now.
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Postby bretzke » Sun Jun 06, 2010 1:11 pm

cheerleader wrote:
patientx wrote:
You have linked a lot of stuff. Maybe you could be a little more specific.


yeah, sorry.
Here ya go, just scroll down to the bottom of the analysis and check out the "reference" section. It has all the papers-
http://www.bmj.com/cgi/content/full/340/jun03_1/c1672

each BMJ analysis has references at the end with facts and figures.



Cheerleader-

When I read the original analysis. I was skeptical due to the economic focus of the article. After reading the supporting references and facts and figures, it certainly appears that good science was used. The conclusions are damning for the MS medical community. Neuros, MS Societies, drug companies and even the FDA have been put on notice.

How will a neuro respond to his patient when they ask, "Why have you been prescribing me a drug that is this ineffective?"

I expect a big pushback soon. This analysis is embarrassing for the MS medical community. I predict a major "cover your ass" campaign from all parties involved.

Brian
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Postby Sotiris » Sun Jun 06, 2010 1:24 pm

Here are the links again together with the reply of the chair of the Scientific Advisory Committee (SAG) of the Multiple Sclerosis Risk Sharing Scheme.
Editorials
The multiple sclerosis risk sharing scheme
A clever achievement, which despite being flawed, has had unintended beneficial consequences
http://www.bmj.com/cgi/content/full/340/jun03_1/c2882

Analysis
Multiple sclerosis risk sharing scheme: a costly failure
James Raftery, professor of health technology assessment
http://www.bmj.com/cgi/content/full/340/jun03_1/c1672

Analysis
Continuing the multiple sclerosis risk sharing scheme is unjustified
James Raftery, professor of health technology assessment
http://www.bmj.com/cgi/content/full/340/jun03_1/c1786

Analysis
Commentary: Outcome measures were flawed
G C Ebers, Action Research professor of clinical neurology
http://www.bmj.com/cgi/content/full/340/jun03_1/c2693

Analysis
Commentary: Scheme has benefited patients
Alastair Compston, professor of neurology
http://www.bmj.com/cgi/content/full/340/jun03_1/c2707

Research
Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator
Mike Boggild, consultant neurologist1, Jackie Palace, consultant neurologist2, Pelham Barton, senior lecturer in mathematical modelling3, Yoav Ben-Shlomo, professor of clinical epidemiology4, Thomas Bregenzer, director, biostatistics5, Charles Dobson, senior projects officer6, Richard Gray, director7
http://www.bmj.com/cgi/content/full/339/dec02_1/b4677

Reply to article «Multiple sclerosis risk sharing scheme: a costly failure»
Risk Sharing Scheme could not yield valid data after only two years follow up (4 June 2010)
Richard J Lilford, Prof of Clinical Epidemiology, University of Birmingham B15 2TT
http://www.bmj.com/cgi/eletters/340/jun ... 672#236605
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Postby concerned » Sun Jun 06, 2010 1:28 pm

jackiejay wrote:I see in Dr. Simka's letter on another thread that he also recommends continuing neurologic medication.....


Well obviously he is working for big pharma and just wants to hurt people.

(with all these studies proving it, how could they not have known?)
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Postby mmcc » Sun Jun 06, 2010 2:01 pm

jackiejay wrote:do you think that the doctors' continuing message to patients will be to continue on your DMD if you appear to be doing well....lesser lesions, no relapses, etc. or will they change their views after this BMJ article's report that these drugs are actually ineffective.
If they don't have you continue whatever you are doing or not doing for a while, there will be no way to judge what change CCSVI has made. My sense is that the docs doing CCSVI procedures want to be able to judge the results, not try to h(hopelessly) seperate out what might be due to CCSVI and what to something else. Very few doctors order bunches of changes at once

I took the posting about the BS meter to apply to the CRAB study, not CCSVI. Was I wrong?

I think everyone is jumping to the conclusion that a government and a Board have their best interests at heart --- ressentialy the same people who have not given approval for CCSVI procedures. Some of the reactions here don't make sense. Why, without even seeing the study itself, are so many people going to take the word of decision makers who are being torn apart for not approving CCSVI procedures. Look who the Board conducting the CRAB study was......

This information needs to be compared with the results of the many other tests of these drugs which have been done. Right now I have no idea who is correct, but while I did not do well on betaseron (DID make MS symptoms worse) or copaxone, other MS drugs did wonders for me.

If the study is correct someone wants to know how their neuro's will explain why they were on ineffective drugs????? Maybe by telling the truth - that the best AVAILABLE information said they should be.

I expect that will be the same answer if CCSVI procedures turn out to not be effective, which much as I hope is not the case, is possible.
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Postby marcstck » Sun Jun 06, 2010 4:28 pm

Wow, so many conflicting agendas and viewpoints on this thread, that have in many places steered this conversation way off path.

As I stated in my previous post, the crux of the BMJ article (which was basically an analysis piece, not a study itself) has to do with the financial implications of the CRAB drugs not meeting projected expectations, and the impact that this failure had on the NHS.

The endpoint the NHS was looking at was disease progression; none of the official US CRAB drug trials used progression as an endpoint, instead using relapse rate and the number of enhancing lesions as seen on an MRI. Because the drugs did impact those two endpoints to a statistically significant factor, they were approved for use in the treatment of multiple sclerosis. There was an overall suspicion that reducing relapse rates and enhancing lesions would impact disease progression, but this was a hope rather than a fact.

There has been increasing evidence that these drugs do not impact disease progression, at least to the amount initially desired. Copaxone actually does come closest to appear to have some significant impact, and some studies have also shown that the drug may have immuno protective properties.

Contrary to an assertion made earlier in this thread, relapse rates are far more readily quantified then disease progression. A relapse is an identifiable event, in which a patient suffers a fairly quick onset of dramatically increased symptoms, which eventually remit to a place somewhere near the patient's initial baseline condition. Progression, on the other hand, is extremely hard to quantify, because it can take quite some time for progression to become apparent by objective means. I've had many neuro visits when I'd known that my disease has progressed, but the progression I felt failed to be evidenced in my neurologic workup.

Copaxone was in fact tested on PPMS patients when it was first introduced. Those tests were initially deemed a failure, based more on the fact that the disease progressed so slowly that there was very little difference between the control and treated group. Later parsing of the data did suggest that copaxone might have some impact on a subset of the PPMS population (men who displayed some signs of inflammation). The same was true for thy Rituxan PPMS trials, which were initially deemed a failure, but upon later review the results turned out to be equivocal for a subset of patients.

The reason why progression was not chosen as an endpoint for the FDA trials of the CRAB drugs was precisely because it is so hard to track.

After more than a decade on the market, there's little doubt that the CRAB drugs do impact relapse rate and enhancing lesions for some MS sufferers, based both on study results, the experience of clinicians, and patient reports. For many patients, the reduction in relapse rate is a huge improvement in quality of life, even if the drugs don't ultimately alter the progression of their disease. The relief from crippling relapses certainly makes the life of successfully treated patients more bearable.

How all this relates to CCSVI is beyond me. The fact that the CRAB drugs do have some effect on the disease in no way disproves the CCSVI theory, and in fact only strengthens it. CCSVI postulates that disrupted hemodynamics in the CNS lead to inflammation in the brain and spinal cord, due to a variety of factors. Drugs that modulate or suppress the immune system would be expected to have some effect given this model.

The attempt to discredit the CRAB drugs to somehow validate CCSVI reminds me of those who try to poke holes in the theory of evolution to somehow prove creationist ideology. If Darwin's original theory does have some identifiable flaws, all that is proven is that our understanding of evolution is imperfect, it in no way relates whatsoever to claims that the earth is only 5000 years old, that men coexisted with dinosaurs in the not so distant past, and that all life on the planet follows the blueprint of an omnipotent deity. Likewise, discrediting the CRAB drugs does nothing to prove or disprove CCSVI. In fact, proving that drugs that impact the immune system have no impact at all on MS would shed some doubt on CCSVI, which is an elegant explanation as to how and why the immune system attacks the CNS tissues.

It's vitally important to take a sober, rational, and impartial look at the constant stream of newly minted MS research information and discoveries. Approaching them with bias, and bending them to fit a set of preconceived notions does nothing to further the cause that one is biased towards.

We must present CCSVI as a rational, fact-based theory that will hopefully soon be backed up by concrete independent research data. We must guard against painting ourselves (the proponents of CCSVI) as a lunatic fringe prone more to hyperbole and hysteria than to rational discourse.

Please note, I'm not calling anyone here a lunatic, I'm just saying that thoughtful analysis trumps knee-jerk reaction more times than not...

Just a quick word on the Cochrane review materials. These are all retrospective studies, which look at research results from completed trials. Cochrane does no trials of their own. While retrospective studies do have value, they can be prone to subjectivity, especially in the choice of which studies are included in the retrospective review. My own experience in looking at Cochrane results has often found their conclusions sometimes questionable. Since I'm not a physician or research scientist, that opinion and two bucks will get me on the subway...

As for the unholy alliance between drug companies, governments, and the medical establishment, I posted an essay on Wheelchair Kamikaze entitled "The Medical Industrial Complex: Sick People Required". Readers seemed to find it interesting, and if you care to have a look, here's the link:

http://www.wheelchairkamikaze.com/2010/ ... eople.html
Last edited by marcstck on Sun Jun 06, 2010 4:33 pm, edited 1 time in total.
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Postby concerned » Sun Jun 06, 2010 4:31 pm

Maybe this thread should have been in the appropriate forum, maybe drug pipeline or something.... Then people might not be comparing it to CCSVI so much.

But otherwise I whole heartedly agree with your post.

Edit: I guess I should say the spirit or the attitude of your post.
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Postby jackiejay » Sun Jun 06, 2010 5:13 pm

I, for one, was not discrediting the CRAB drugs to validate CCSVI....I was sickened to read that there is not much credit given to these drugs at all...according to the BMJ....I can see the connection, according to your hypothesis....that if they are somewhat effective that helps the CCSVI theory....we are only commenting on the findings stated in the BMJ....I was told it is a highly respected journal, maybe it's not.....but it all comes back to CCSVI and the hope that it is the major part of the answer we are all looking for...
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