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Someone in the MSWorld forums posted a comment that the study may also be suffering from a political motivation/bias. The new UK government is making a push to cut costs, and this report may be the foundation for reducing costs on MS drugs. Just as pharma has certain motivations, so do governments. Just something to consider when pondering the objectivity of this report.

Nevertheless, I'm not a UK citizen and am unfamiliar with the NHS. Maybe one of our UK members could shed some more light on the politicization of the agency and this report in particular?

costumenastional wrote:

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.

Not at all accurate. Personally, Novantrone, Tysabri, and Zenepax - all of which are immune suppressants of one type or another not only stopped my downhill slide, the were responsible for major improvements.

How am I so sure? Because when I had to stop them for various reasons the downhill slide came roaring back.

This is the case for many, many people.

I agree mmcc. The drugs out there are far from perfect but they are better than what was around thirty years ago. You will not convince anyone on here though.

Here is a link to the Direct-MS 2005 article on the value of MS drugs
http://www.direct-ms.org/magazines.html#objective

How surprising that this article comes from Ashton Embry.

scorpion wrote:How surprising that this article comes from Ashton Embry.

Actually, not very surprising, scorpion. An articulate and well-reasoned posting from a man who has been working incredibly hard for over a decade, raising hundreds of thousands of dollars to fund research, looking outside the pharma box, while helping thousands of pwMS find remission and relief from MS symptoms through diet, supplements and lifestyle. For free. Because his son has MS and he cares enough to dig in and help others.

Thanks, Dr. Embry. Here's the link again. Worth a read.
http://www.direct-ms.org/magazines.html#objective
cheer

cheerleader wrote: looking outside the pharma box, while helping thousands of pwMS find remission and relief from MS symptoms through diet, supplements and lifestyle. For free.

Is that statement something you can actually substantiate or are you "just sayin'" again?

while i don't agree with the embry camp on all counts, i can definitely say that i personally have benefited from nutritional treatment and that in some cases there are decades of scientific literature to back up the nutritional assertions.

FlashHack wrote:

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.

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!!"

The size of the cohorts isn't the only thing to consider regarding systematic bias. As Mark pointed out, the "control" group was apparently a set of patients in Canada. In other words, it seems the controls were not only living in a different part of the world, they were seeing different doctors and having their EDSS levels measured by a completely independent team. That's probably OK for a legal reference point in a drug pricing contract, but isn't really solid science if you're trying to determine actual drug effectiveness. There's a reason why real drug trials use double-blinding and placebo controls: there is plenty of evidence that you'll get unreliable results if you don't.

/Scut

jimmylegs wrote:i can definitely say that i personally have benefited from nutritional treatment and that in some cases there are decades of scientific literature to back up the nutritional assertions.

Despite the million/billions spent developing, testing and promoting them in another current thread people are showing that the real efficacy of the crabs isnt beyond question. You're saying that a higher level of documentation can be shown against the MS disease process through diet and nutrition?

Marc

I think the interesting aspect is not the comparison against the control group but the efficacy of the drugs against the predicted efficacy.

In other words the group in the study did not achieve the reduction in progression that the drug companies predicted based on previous trials.

Given the predicted efficacy would not be that amazing (reading the Cochrane analysis of interferons suggests they waiver very close to being statistically insignificant depending on how drop outs are classified) its quite disappointing that such a large trial doesn't, at the very least, come close to the predicted progression figures.

I just wish the article would focus more on publishing the data than worrying about taxpayers being ripped off..

Lack of double-blinding and placebo controls is one criticism that cannot be raised in this instance.

Both blinding and placebo controls are ways of controlling the effect of the patient and doctors expectations. This effect is always to inflate the results, to make the drug seem more effective than it really is. No patient or doctor ever hopes the patient will get worse.

If you applied some statistical technique to remove such effects from these results you would make the drugs appear even more ineffective.

Before this publication I would have been willing to believe that there was a real positive effect buried in the results but that it was very small and not noticed by the patients. Which I think is similar to dreddk’s POV. That would be consistent with the results already published by the Pharmaceutical Companies. The much larger number in this trial should also have made the effect easier to see as random variations would tend to cancel out better in the larger sample.

But the truth is either there is an uncontrolled bias in these results or there were uncontrolled biases in the previous trials. The chance of a consistent bias in these results is vanishingly small. It is inescapable that all previous smaller scale trials are now in doubt. I might say this is not a new POV. For an unbiased account I would recommend the summary of previous research by the Northern and Yorkshire Regional Drug and Therapeutics Centre here:

http://www.nice.org.uk/nicemedia/pdf/Or ... il2000.pdf

Political Motivation Bias

I am afraid this cannot apply to the current UK Govt. This scheme was set up by the previous government and the results being discussed were published in December last year before the current govt. took office. But they will undoubtedly now seize on it. To be seen to be pursuing a large refund of the tax payers money while at the same time defending the NHS and MS patients will suit them fine.

The implications of this research cannot be overstated. It casts real doubt on the conduct of Drug Companies in reporting previous trials and destroys the basis for prescribing these drugs at all in the UK. And this is not just for one dmd but the four biggest!

Please take heed. Sorry for the long post but I think it is worth it. According to Robert Park PHD these are the seven warning signs of Bogus Science.

1. The discoverer pitches the claim directly to the media.

The integrity of science rests on the willingness of scientists to expose new ideas and findings to the scrutiny of other scientists. Thus, scientists expect their colleagues to reveal new findings to them initially. An attempt to bypass peer review by taking a new result directly to the media, and thence to the public, suggests that the work is unlikely to stand up to close examination by other scientists.


Some scientific claims avoid even the scrutiny of reporters by appearing in paid commercial advertisements. A health-food company marketed a dietary supplement called Vitamin O in full-page newspaper ads. Vitamin O turned out to be ordinary saltwater.
2. The discoverer says that a powerful establishment is trying to suppress his or her work.
The idea is that the establishment will presumably stop at nothing to suppress discoveries that might shift the balance of wealth and power in society. Often, the discoverer describes mainstream science as part of a larger conspiracy that includes industry and government.
3. The scientific effect involved is always at the very limit of detection.

4. Evidence for a discovery is anecdotal.

If modern science has learned anything in the past century, it is to distrust anecdotal evidence. Because anecdotes have a very strong emotional impact, they serve to keep superstitious beliefs alive in an age of science. The most important discovery of modern medicine is not vaccines or antibiotics, it is the randomized double-blind test, by means of which we know what works and what doesn't. Contrary to the saying, "data" is not the plural of "anecdote."
5. The discoverer says a belief is credible because it has endured for centuries.

There is a persistent myth that hundreds or even thousands of years ago, long before anyone knew that blood circulates throughout the body, or that germs cause disease, our ancestors possessed miraculous remedies that modern science cannot understand. Much of what is termed "alternative medicine" is part of that myth.

Ancient folk wisdom, rediscovered or repackaged, is unlikely to match the output of modern scientific laboratories.
6. The discoverer has worked in isolation.

The image of a lone genius who struggles in secrecy in an attic laboratory and ends up making a revolutionary breakthrough is a staple of Hollywood's science-fiction films, but it is hard to find examples in real life. Scientific breakthroughs nowadays are almost always syntheses of the work of many scientists.
7. The discoverer must propose new laws of nature to explain an observation.

A new law of nature, invoked to explain some extraordinary result, must not conflict with what is already known. If we must change existing laws of nature or propose new laws to account for an observation, it is almost certainly wrong.

But as I finished the list, I realized that in our increasingly technological society, spotting voodoo science is a skill that every citizen should develop.

Scorpion,

Very well put.

AMcG wrote:Lack of double-blinding and placebo controls is one criticism that cannot be raised in this instance.

Yes it can, since the study was neither double-blinded nor placebo controlled.

AMcG wrote:Both blinding and placebo controls are ways of controlling the effect of the patient and doctors expectations. This effect is always to inflate the results, to make the drug seem more effective than it really is. No patient or doctor ever hopes the patient will get worse.

This is not correct. Placebo controls, for example, are also used to try to reduce the impact of uncontrolled variables or side-effects between treated and untreated groups. For example, if you're measuring "quality of life", those getting the CRABs may score worse due to the injection reactions, but that doesn't mean their MS is getting worse. Furthermore, your assertions about biased results always being positive is also provably false. Don't forget that the Canadian control group also consisted of patients. Wouldn't their doctors be hoping just as hard for their own patients to get better?

AMcG wrote:If you applied some statistical technique to remove such effects from these results you would make the drugs appear even more ineffective.

There are no valid statistical techniques to reliably remove unknown biases or flaws in experiments. This is why it's so critical for experiments to be done properly if you want to reach a robust scientific conclusion.

AMcG wrote:Before this publication I would have been willing to believe that there was a real positive effect buried in the results but that it was very small and not noticed by the patients. Which I think is similar to dreddk’s POV.

It is inescapable that all previous smaller scale trials are now in doubt. I might say this is not a new POV. For an unbiased account I would recommend the summary of previous research by the Northern and Yorkshire Regional Drug and Therapeutics Centre here:

http://www.nice.org.uk/nicemedia/pdf/Or ... il2000.pdf

Uh, did you actually read this summary? It clearly states in its conclusion:

NHS Health Technology wrote:

• Beta interferons and glatiramer reduce relapse frequency in a dose-related manner compared to placebo, the reduction being approximately 30% with the licensed doses. This effect is seen in relapsing remitting MS and secondary progressive MS.
• Interferon beta -1a and -1b and glatiramer produce modest reductions in progression of disability. The data suggest a dose-response relationship for interferon beta -1b and -1a. Studies in secondary progressive MS indicates that patients with a relapsing pattern of disease and/or EDSS scores ≤ 5.5 are more likely to benefit from treatment.
• Beta interferons produce reductions in MRI measures of burden of disease and disease activity and there is evidence of dose-response. Unpublished data also indicate a beneficial effect for glatiramer, although this may be less marked.

Where that summary is less positive is in the cost effectiveness of MS treatment. They attempt to quantify how much quality-of-life improvement people get for the money being spent. Basically, it concludes that MS treatments are very expensive for their modest benefits, so maybe it's a better use of NHS money to let MS patients have their relapses and instead treat other illnesses. That's not saying they don't work, just that maybe they aren't worth the cost to the NHS. That's actually a rational argument, though it kind of sucks for pwMS.

AMcG wrote:The implications of this research cannot be overstated.

Sure they can. Here, let me try: this research will revolutionize the finance and hatmaking industries as we know them. Seriously, it can be overstated, and has been several times in this thread. These results are important and need more explanation and analysis, but they aren't proof that all prior studies are flawed.

AMcG wrote:It casts real doubt on the conduct of Drug Companies in reporting previous trials and destroys the basis for prescribing these drugs at all in the UK. And this is not just for one dmd but the four biggest!

Oh, please, it does no such thing. This study has numerous methodological weaknesses, including the fact that it's not a randomized, double-blind, placebo controlled study, unlike many of the prior studies you believe it refutes. It does raise some interesting questions, and I'll be interested to see how this plays out, but it's not a smoking gun. The big failure here was the prior UK administration agreeing on an expensive gamble with the drug companies (using taxpayer money, I believe), and then the government apparently failing to collect on what was owed them under the terms of their agreement. One take-away is that when you have high-stakes financial negotiations between politicians on their way out, and a private company that's in it for the long haul, you can bet the taxpayers will lose.

And sadly, I think these kinds of shenanigans are bad for CCSVI, since they tend to make both the public and health care providers doubly-suspicious of treatments that lack extensive evidence of effectiveness.

/Scut