This Is MS Multiple Sclerosis Community: Knowledge & Support

I have always been skeptical of the information provided by the CRAB drug makers when it came to their clinical trials. Here is an example involving a recent trial of Copaxone but I'm not sure just what one it was.

On Monday April 25th, there was a PBS preview party in Washington State for the airing of a documentary on MS titled The Unwanted Companion, The Mystery of MS. The event was sponsored by the MS Hub and TEVA. Afterwards they had a question and answer session and a patient in the audience asked if they would ever have any drug available for Primary Progressive MS patients. Dr. Bowen, a prominent neuro in Washington, answered the question like this....paraphrased since the people listening didn't have a tape recorder....the response was that unfortunately Copaxone had been studied for three years in progressive MS and that TEVA had spent 45 million dollars on the study and it wasn't a case that the Copaxone didn't show effect but rather the problem was that the placebo group didn't change, so unfortunately it was a poorly designed study.

Now since when did they look for changes in the placebo group to determine if a drug is working properly??!! That group should remain a constant and the results compared with those who took the drug should be what is analyzed. The two people who attended this presentation and provided me with the information, thought that possibly the placebo group may not have been given anything to alter their results in an unfavorable relationship to the Copaxone. For instance, if you gave the placebo group sodium along with their supposedly inert drug, then their T2 MRI's could show extra lesion activity and thus inaccurately demonstrate that the Copaxone group had fewer lesions. And Dr. Bowen also made the comment that the trial was not properly designed!!! How on earth can a company like Teva not have a properly designed trial after the hundreds of MS clinical trials done in the past 15 years?

This info was quite shock to me and I have no idea if that indeed is what happened but I guess speculation can include almost anything. Would be interested in any opinions on this.

Harry

Harry, this is old news. Not much has been shown to help PP to date.

The PROMiSe trial: baseline data review and progress report.

Wolinsky JS; PROMiSe Trial Study Group.

University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA. jswolinsky@aol.com

The PROMiSe trial is a multinational, multicentre, double-blind, placebo-controlled trial evaluating the effects of glatiramer acetate treatment over 3 years in patients with primary progressive multiple sclerosis (PPMS). A total of 943 patients were enrolled, and all those remaining on-study had completed at least 24 months as of October 2002. Baseline clinical and MRI characteristics and select correlations are reported here. A total of 3.9% of patients exhibited confirmed relapse over 1904 patient-years of exposure, indicating success of efforts to exclude relapsing MS types. Of the 26.3% of patients who have prematurely withdrawn from the study, only 36% discontinued after meeting the study primary endpoint of disease progression. The progression rate in patients in the low Expanded Disability Status Scale (EDSS) stratum (3.0-5.0) observed thus far is markedly lower than the 50% annual progression rate estimate used for determining size and statistical power of the trial; progression was observed in 16.1% of patients with 12 months of study exposure. These early findings raise some concern about the ability of the trial to demonstrate a significant treatment effect, and suggest that the short-term natural history of PPMS may not be as aggressive as previously assumed.

Peter

Peter,



I know the trial was done a while ago but my point here wasn't how long ago but Dr. Bowen's comment on the placebo group....in that it didn't change during the trial! In other words, because the placebo group didn't change and the results weren't very good, the trial design was determined to have been poor. I guess they didn't consider the results poor due to the fact that Copaxone isn't much good in the treatment of MS patients ...as stated by the Cochrane Report. It all goes back to how the CRAB makers relate info to us about their trials....if the results aren't very good, it's not the drug's fault, it's for some other reason.

Harry

Hi Harry,

But those remarks make some sense to me. First I take it that the ABC drugs at best slow progression.

If you have a double-blinded placebo controlled trial, and you are measuring the difference between the placebo group and treatment group in terms of EDSS, and the placebo group doesn't progress, then it is not possible to demonstrate the treatment slows progression, right?

Or consider in an RRMS trial, if nobody in the placebo group has a relapse, it isn't possible to show that the treatment reduces relapses relative to placebo.

If the treatment is supposed to improve people's EDSS scores, rather than merely slow their decline, then it's a different story.

The same thing happened in a major trial with Cytoxan in the early 90s in PPMS. The placebo group for the most part remained stable for two years.

On the other hand, the only problem I see in the trial design is somehow doing a better job of limiting participation to people who are actually progressing, or perhaps relying on a more sensitive barometer than EDSS.

Mark

Hi Mark,

You make some very good points about double blind trials which leads me to this comment.

I had heard that some of the earlier CRAB drug trials ended up with this very situation...the placebo group did not change or changed so little that there couldn't be a comparison made with the drug being tested. That certainly didn't look good for the particular drug in the trial so the results were scrapped and never published. After all, if the patients getting nothing did as well as or better than the patients receiving the drug then that was very bad if you were the drug producer!

Now I also heard (certainly no confirmation of any kind) that the people conducting the trials added substances to the placebo so as to make the actual drug look better. Clinical trials do not have to list the contents of the placebo which is supposed to be totally inert. One example was sodium which supposedly will make more lesions appear in T2 weighted MRIs. Sounds kind of extreme but I certainly don't make this info up but only relate what I have heard.

The Cochrane Group, which analyzed the earlier Copaxone trials and came up with the report that Copaxone was totally useless in the treatment of MS, hinted that Teva "dredged" the data of these trials. They created positive info which simply wasn't there and the Cochrane Group are MS researchers. So you really start to wonder about placebo effect and how it can be manipulated and used in the wrong way.

And then Dr. Behan comes out with his Pathogenesis of MS and states that the CRAB drugs aren't worth a damn. No wonder MS patients don't know just who to believe.

Harry

Harry,

If you add any active substance to a placebo, it isn't a placebo anymore. Placebo is by definition an inactive substance that will have no physiological effect on the body or disease in question. There IS such a thing as "active placebos", such as caffeine or atropine, but they are labeled as such.

So either

a) they are fradulently claiming that they used placebo when they in fact did not, which would be a huge charge of scientific misconduct with legal charges warranted

or

b) You are mistaken.

Daunted,

You are absolutely right...a placebo SHOULD NOT have any active ingredient in it at all and if something IS added, then it isn't considered a placebo any longer.

And you are further correct in that adding something to a placebo and not saying anything is a terrible mis justice. Now that brings us to the integrity of drug companies that are conducting these trials. Can anyone state that all the drug companies are beyond doing something like this?

I don't know if you have ever visited the cafepharma website where many of the posters are reps from the various pharma companies. If you were to believe 1/4 of what these reps state, then there is no question about how some of these companies deliberately skew the data in their trials.

Again, it's not me who is making these comments, it's other people. The info is either correct which makes some of these companies "crooks" or I am wrong and we believe everything that the pharmas tell us!

Remember how many people, on this very site, accused me of rumor mongering and spreading false info about Tysabri for months and that I had an "agenda" against Biogen. The unfolding events eventually proved otherwise. I shudder to think if this recent info I was given is even 25% correct!!

Harry