article "MS drug trial a fiasco"

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Postby bretzke » Fri Jun 04, 2010 6:18 pm

jackiejay wrote:is this information totally reliable?....is this BMJ widely read....don't know anything about it....would doctors in Canada and U.S. read this?


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Been around since 1840.

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Postby tazbo » Fri Jun 04, 2010 6:19 pm

Source: Teva Pharmaceutical Industries Ltd.
Bayer HealthCare Pharmaceuticals announced today
Please see full Prescribing Information and Patient Medication Guide for AVONEX. ©2008 Biogen Idec. This site is intended for patients who are residents of the United States, Puerto Rico, and US territories. AVONEX and MS ActiveSource® are registered trademarks of Biogen Idec.

I agree...these news releases are put out buy (Freudian...lol) the manufacturers...not impartial test data.
I assume that was why you just posted links?
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is it all meaningful?

Postby prairie » Fri Jun 04, 2010 7:46 pm

in the full two year results report:
Conclusions
It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the "no improvement" rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.
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Postby patientx » Fri Jun 04, 2010 7:57 pm

cheerleader wrote:Because most drug trials are funded by drug companies, the true efficacy of these drugs is often overstated.

I think we all know that pharmaceutical companies are not the most noble of institutions, and that the regulatory process is far from perfect. But this is not a fair or accurate statement. At least the U.S. FDA has strict guidelines on what drug manufacturers can say about what a drug does (I have never lived in Britain, so I cannot say what happens there). The drug must meet some primary endpoint, determined before a trial. And the CRABS were approved based on a reduction in relapse rate, and that's all they ever claimed. Biogen did show that Avonex resulted in a slightly lower rate of progression, so they are able to advertise that. Everyone, me included, will agree that a 30% reduction in relapse rate just isn't good enough. But I haven't seen anything else claimed by Teva for Copaxone, or Serono for Rebif.

I think it is also important to keep in mind that both the interferons and Copaxone went through several trials, not just the phase III trials. Those early interferon trials were funded by the NMSS. And Copaxone showed some efficacy in trials well before Teva got involved.

...and found out that the drugs were worth NOTHING, since patients on them did worse than the controls.

Worth nothing? Remember, these drugs were approved when there wasn't even anything to reduce relapse rates. I think many who have suffered through a severe MS relapse might disagree with you.

cheerleader wrote:scorpion,Maybe not conspiracies, but the pharmaceutical companies are at the forefront of MS research as donors to the MS Societies and major universities.


This statement is just wrong. Contributions to the NMSS from pharmaceutical companies amount to about 4% of its revenue. And for most major universities, most of their basic research funding does not come from drug companies; it comes from the NMSS or other organizations, like the VA (I discussed this with a trial nurse at my last visit to a major university hospital's MS center). True, these universities may apply if a drug company is running a clinical trial; but the hospital will have an independent principal investigator, and the trial will be done under the supervision of the hospital IRB (the same IRB's that have been much maligned in other threads in this forum).
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Postby mmcc » Fri Jun 04, 2010 9:09 pm

babiezuique wrote:MMCC

I'M from Canada. Here we don't ''lawsuit'' as you do in the state. We have a different medical system than yours... When a canadian is cling for a lawsuit... it is not the same song than when it is an american.

CCSVI as nothing to do with drugs.... it is a condition. That can be tested and mechanicaly treated.
Of course CCSVI can be tested. Read what Dr. Zamboni himself said - that it needs more testing.

babiezuique wrote:Do you seriously think that we have to be quiet like a beaten child....in front of this historical scandal?
We don't know each other, but this is something that anyone who knows me would double over in hysterics about. I have never been quiet about anything in my life. In fact I am about to launch a one person campaign against Biogen.

And when the option to take Tysabri was being denied to people I showed up and testified at the FDA hearing. You think I am "quiet like a beaten child?" What have you done? And complaining on this forum doesn't count - we all do that - so what - we are complaining to each other - and we are not the problem.

I will also gladly do what I can to push CCSVI to become a viable option for people - meaning covered by insurance, since most people cannot afford to fly to Poland. I feel that I am starting by putting my body where my mouth is and having it done.

I didn't say one word about being quiet. What I said is that IRB's are afraid of lawsuits and that when we scream lawsuit about everything - as is too often done in the US - of course people get more and more afraid of lawsuits.

That has nothing to do with "being quiet." Suing is too often a lawyer employment act - something I am not interested in. On what basis would most people sue? If you paid for the drugs yourself that would be one thing or if you were harmed that would be another, but most people have done neither. Its not like there were a lot of other drugs out there at the time so it can't even reasonably be claimed that we were denied other choices since we tried what were then "new" drugs.

The research looked promising.

And once again - a lot of the anger is IMHO being misdirected. You are mad because the pharma companies did the testing???? Fine, who should have done it? IMHO the answer is the Federal government. I don't get why there is no anger directed at the one place which should be developing drugs AND testing them.

The way the system works now if the pharma companies don't test them, they don't get tested at all, and for the most part if they don't develop them, they don't get developed at all.

And yes, I will be VERY angry if it turns out that this study says what it appears that it says. Has anyone actually seen the study? I took betaseron and copaxone, like many others.
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Postby eric593 » Fri Jun 04, 2010 9:13 pm

One has to remember too that people under the public healthcare system were demanding that the system pay for these meds. The resistance was that NICE did not believe that the cost for them was substantiated by benefits to the patient.

But patients didn't care. SOMETHING was better than nothing. So they set up this system so that the healthcare system agreed to pay for the meds under supervision so it could be evaluated whether or not the cost was justified by patient benefit.

It looks like in the end, it wasn't. But try telling patients you're taking away their meds. I'm sure they really had no choice but to continue to pay for the meds for patients because the backlash would have been enormous if people would have been cut off.

The cost/benefit analysis is also mathematic too, so it wouldn't take into consideration individual successes, it only analyzed as a group whether improvement to patient was worth the cost. How you determine that is strictly economic formulas, it has no emotional component factored in whatsoever.

Yet, even though the benefits was not determined to justify the healthcare cost, they were in a curious predicament of feeling that they probably couldn't just take the drugs out of the healthcare system, and maybe more time might show some benefit that outweighed the cost. I doubt the drug companies would have been willing to reduce the drug costs regardless of what the NHS determined to be the benefit/cost ratio. They knew patients were depending on the drugs by then, so the government was really in a lose-lose situation. Pay for the drugs, or risk a major public condemnation from patients who had been on the drugs for a very long time. Because also, the drug companies have continued to put out continuing benefits from the drugs from continued use. So the NHS would have been up against a LOT of research that showed something different than what their own evaluation was finding in terms of drug benefit.
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Postby cheerleader » Fri Jun 04, 2010 9:41 pm

The fact that the prices would have had to be cut to zero (given outcomes were less than those of the controls) is hardly a reason for not proceeding. If patients are to continue to receive drugs through the scheme, big price cuts seem necessary.

http://www.bmj.com/cgi/content/full/340/jun03_1/c1672

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.
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Postby eric593 » Fri Jun 04, 2010 10:05 pm

cheerleader wrote: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


A Cochrane review some time ago suggested that copaxone wasn't any better than placebo.

The drug company continues to put out research showing a benefit by its use, which increases over time.

The NHS found the cost not justified by patient benefit.

The FDA and other governmental regulatory bodies have found a benefit to the meds and licensed them for use.

Who you gonna believe? It's never clear cut or black or white. I don't think this is exactly a smoking gun situation.
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Postby FlashHack » Fri Jun 04, 2010 10:38 pm

This brings up an important distinction:

1) Reduction in relapse rates
2) Reduction in lesion formation
3) Progression in EDSS scores

It is worth noting that this study looked at EDSS scores (3). I remember that the interferon treatments all touted reduction in relapse rates (1). Perhaps these drugs merely change the nature of how the condition progresses by changing the nature of a "relapse." Do they just mute the precipitous nature of relapses and turn MS into a more steady decline instead? A slope vs. a staircase?

I've been on Rebif for 4 years now and over the last year, it has been hard to put my finger on any specific relapse event, but I know that my walking and balance are getting gradually worse.

Nice of them to smooth out our decent into hell. I always did like a good slide.
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Postby marcstck » Sat Jun 05, 2010 1:06 am

I've read and reread the piece in the BMJ. It's major focus is that an agreement reached between the NHS and the drug companies to revisit the price paid for the CRAB drugs once efficacy data was available was never put into action. It concludes that the price paid for the drugs is not worth the efficacy that they display. It does not state that the drugs themselves are worthless.

The article presents some contradictory evidence, stating that the control group (which were 5000 untreated Canadian patients, not their British counterparts) showed less progression than the group on the DMD's. Later in the piece, though, it states that after one year on the drugs, 38% of those using the drugs showed an improvement in their EDSS.

None of the phase 1, 2, or 3 CRAB drug trials used EDSS as an endpoint, instead using relapse rates and enhancing lesions as seen on MRI. EDSS is notoriously hard to quantify, which is why very few drugs have been tested on patients with progressive disease, who typically do not suffer relapses or enhancing lesions.

My take away from all of this is that the NHS has concluded that they overpaid for the drugs, based on the fact that the drugs were less effective than originally predicted. The scant amount of data cited in the article begs for a more thorough disclosure of the trial results, but my understanding of the piece as it stands does not lead me to conclude that the CRAB drugs can be declared entirely worthless.

They are obscenely expensive given the modest efficacy they have displayed, but the fact is that many patients have experienced fewer relapses and less enhancing lesions as a result of taking these drugs. Whether or not they impede progression has never really been ascertained.

I do think that the CRAB drugs are nothing more than a sophisticated form of symptom management, and do nothing to address the root causes of the disease. In that respect, they've taken the eyes of researchers off the real target, and focused them on the "autoimmune theory" for far too long.
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Postby costumenastional » Sat Jun 05, 2010 2:49 am

marcstck wrote:I do think that the CRAB drugs are nothing more than a sophisticated form of symptom management, and do nothing to address the root causes of the disease. In that respect, they've taken the eyes of researchers off the real target, and focused them on the "autoimmune theory" for far too long.


I couldnt agree more of course. And this raises the question: Is MS autoimmune?
No it is not. If it was, immunosupression would stop progression. Please believe me. It does not.
As for immunomodulation...well, lets say that if it was working there would be no need for Tysabri, Campath, Rituximab etc...
All immunosupression does (sometimes) is reducing relapses and lesion numbers. All in all, it puts the brakes on inflammation by leaving the body unprotected from everything else.

For us, cure is the dream which will end the nightmare.
For them Cure equals loss of 10 billion per year.

This is the reality and this is why we must fight for more research who will address the REASON this is happening to us.
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Postby Vhoenecke » Sat Jun 05, 2010 4:38 am

Went on LDN when I came home and quit Copaxone.

http://www.ldninfo.org/

Generic drug that actually works.


Val
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Postby cheerleader » Sat Jun 05, 2010 9:09 am

Obviously, the BMJ articles are merely responses to the independent research which has been presented to the NHS. We have not seen their data, however this chart was attached to one of the papers--

It shows the percentage of patients treated/not treated and EDSS progression--actual and expected with treatment. The discrepancy between what was expected/promised and the actual EDSS progression while on CRABS is surprising, especially around the 6 on EDSS.

http://www.bmj.com/cgi/content-nw/full/ ... b4677/FIG2

Again, would love to see all the numbers, not just one chart out of context. Look at the references listed on the BMJ papers--some more of the research is there.

I would also like to see all of the specific efficacy research, especially as it pertains to Jeff's drug of choice, Copaxone, which he and his neuro believe has kept a lid on his inflammation. However it appears the drug companies can keep this research from being published. (See the 2006 BBC article I linked above.)

There has been scant independent review of medications for MS. If I'm not mistaken, I believe Cochrane is it. And as Marc has pointed out, if the CRABS are really more about symptom management than "disease modifying" treatment, the drugs must be billed and monetized as such.
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Postby FlashHack » Sat Jun 05, 2010 9:14 am

marcstck wrote:I've read and reread the piece in the BMJ. It's major focus is that an agreement reached between the NHS and the drug companies to revisit the price paid for the CRAB drugs once efficacy data was available was never put into action. It concludes that the price paid for the drugs is not worth the efficacy that they display. It does not state that the drugs themselves are worthless.

The article presents some contradictory evidence, stating that the control group (which were 5000 untreated Canadian patients, not their British counterparts) showed less progression than the group on the DMD's. Later in the piece, though, it states that after one year on the drugs, 38% of those using the drugs showed an improvement in their EDSS.

None of the phase 1, 2, or 3 CRAB drug trials used EDSS as an endpoint, instead using relapse rates and enhancing lesions as seen on MRI. EDSS is notoriously hard to quantify, which is why very few drugs have been tested on patients with progressive disease, who typically do not suffer relapses or enhancing lesions.

My take away from all of this is that the NHS has concluded that they overpaid for the drugs, based on the fact that the drugs were less effective than originally predicted. The scant amount of data cited in the article begs for a more thorough disclosure of the trial results, but my understanding of the piece as it stands does not lead me to conclude that the CRAB drugs can be declared entirely worthless.

They are obscenely expensive given the modest efficacy they have displayed, but the fact is that many patients have experienced fewer relapses and less enhancing lesions as a result of taking these drugs. Whether or not they impede progression has never really been ascertained.

I do think that the CRAB drugs are nothing more than a sophisticated form of symptom management, and do nothing to address the root causes of the disease. In that respect, they've taken the eyes of researchers off the real target, and focused them on the "autoimmune theory" for far too long.
Mark, as usual a very balanced and thought-out response. The fact that EDSS is "notoriously hard to measure" should not play into anything here as the measurement difficulties would exist in both cohorts (besides it could easily be argued that relapse rates are equally hard to measure and perhaps even more subjective). The size of these cohorts, as noted in the article, is unprecedented, making any systematic measurement bias highly unlikely. On top of that the EDSS scores were not just equal to the untreated population, THEY WERE SIGNIFICANTLY WORSE. I would invoke the ghost of the old lady in the Wendy's commercials of the 80's and say, "WHERE'S THE PLACEBO EFFECT!!"
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