First, the study was designed and all protocols were agreed with the FDA. IMHO, the charge of manipulation is unfounded (as you'll see from my other comments below), but the reader can make their own judgment.
The study protocol will state that patients were randomized into the various study groups. But this is all that FDA or the Institutional Review Board gets involved. No one from these agencies will follow-up to insure that true randomization was done. It is public knowledge some of the corruption in the FDA, for instance the FDA trying to turn a blind eye on the heart attacks resulting from Vioxx, or the FDA allowing Rezulin to remain on the market for 30 months after the FDA had been receiving reports of liver failure and death due to Rezulin. Four of the 12 voting members of the FDA advisory panel that approved Rezulin, and voted to keep it on the market for another 30 months, had financial ties to the company that made Rezulin, Warner Lambert. According to the Cochrane Review, the FDA stated that they suspected that Teva had done “data dredging” when they submitted the information to the FDA seeking approval for Copaxone. Despite this possibility of “data dredging” the FDA approved Copaxone rather than required further disclosure of data.
Second, the bold statement that MRI findings and clinical status of patients is simply a fact, and all of the drug makers and the FDA agree that this is a fact.
Exactly, there is no correlation between the MRI findings and the symptoms or progression of the disease. So there is no logic or scientific reason to continue to determine that a drug is effective in treating MS based on the drug’s effect on the lesions in the MRI. What is the point of saying your MRI's are showing great pictures of reduced lesions but your symptoms or MS in general aren't getting any better at all?!
Third, the FDA and many physicians believe that MRI findings ARE clinically significant, its just tying them to disease progression that is unknown.
“believe”, meaning not yet proven. They used to “believe” that germs didn’t cause disease or illness, until science proved otherwise.) So after hundreds of millions of dollars of research, science has still been unable to tie MRI findings to disease progression. Yet this warrants MS patients and or their insurer, paying billions of dollars for these so called treatments that continue to fail to beneficially impact the disease progression or the symptoms that continue to plague the MS patient? And it is these same people who refuse to acknowledge the science that the immune system is not attacking the myelin and not the sole cause of the symptoms in MS (Behan, Persani, Prineas, Barett)
Comment: The FDA and Biogen Idec/Elan agreed that EDSS scores would be the primary endpoint of the 2yr P3 study, and that 1 yr data are too early to assess improvement in EDSS scores. My problem is that the poster is criticizing the companies for not reporting something which the Companies never intended to report at year 1. The primary endpoint of Year 1 was relapse, with the MRI as secondary endpoints.
First of all, the study’s primary endpoint is determined and SET prior to the commencement of the study. The fact that Biogen Idec/Elan decided to submit the data early to the FDA (at 1 year versus 2 year), then they should have had convincing data regarding their primary endpoint and that was the EDSS scores. Iif the EDSS scores would have shown improvement then there wouldn’t have been any reason not to disclose this information since it was after all the primary endpoint. This is a big no-no in scientific research, but unfortunately the FDA allowed it.
The EDSS measures a change in symptoms such as bladder and bowel incontinence, walking, dexterity, etc. These are measured in 0.5 increments with 0=no symptoms and 10=death. It would be very easy to determine a change in the EDSS score within 1 year or less, but it would not be as easy to determine a decrease in the frequency of exacerbations as frequency can vary from 0 to several exacerbations a year, so only over a prolonged period of time could it be determined if the frequency was altered and then it is only a probable determination because unless you have a clone of each person could you know if they would have had an exacerbation without the medication. Also as the duration of the disease increases, the frequency of exacerbations decreases without any drug intervention. But as the disease duration increases, generally so does the symptoms, so a change in the EDSS score is a better indicator of drug effect.
Some of the other MS drugs have done this, submitted data early to the FDA rather than complete the full time allotted for the study and submit all of the data. Berlex did this exact same thing when they submitted their information on Betaseron for FDA approval. The reason Berlex and most companies do this is because the results are not promising for the longer term. I quote from the Physician’s Desk Reference 2001 regarding Betaseron, “At the end of 2 years on assigned treatment, patients in the study had the option of continuing on treatment under blinded conditions. Approximately 80 % of patients under each treatment accepted. Although there was a trend toward patient benefit in the Betaseron groups during the third year, particularly in the 0.25 mg group, there was no statistically significant difference between the Betaseron-treated vs. placebo-treated patients in exacerbation rate, or in any of the secondary endpoints.” Thus, Berlex decided to submit only the first two years of data.
I don't understand the criticism in the quote, but I do note that the writer makes assumptions about the data, stating twice 'most likely.' It is generally not good to make assumptions when analysing data.
If Biogen Idec/Elan would divulge all of the information such as the median EDSS score in the various groups at baseline, baseline lesions, etc then a person would not have to use terms such as “most likely”. You said that, “We do not know how many lesions the patients had prior to the study, but it is quite possible that many/most patients had lesions (since this is one of the tools used to dx MS).” How is “most likely” different than saying “quite possibly”? You stated that “It is generally not good to make assumptions when analyzing data”. Yet that is what you just did! In fact, that is what the FDA, physicians etc are doing when they analyze the data from the MRI findings and then assume that this data has an impact on the clinical status of MS.
First, 'median' is a sample statistic which means half of the sample are less than the median value, and half of the sample are more than the median value. It is important to know this, therefore, new lesions could have indeed formed, while some lesions may have gone away.
That is not what the study was measuring, it was measuring, the median change was 0.0. What benefit is gained if you lose a lesion but gain one ? Furthermore, the T2-hyperintense lesion measurements showed a difference between the Tysabri group and the placebo group, but remember that the T2 weighted scans are not very dependable because they will show an abnormality or change by any change in tissue composition. In other words, they pick up too much noise and variability. The Gadolinium enhancing lesions are much more accurate for finding new or enlarging lesions and active lesions. Note that there was no difference in change between the Tysabri group and the placebo group with the Gd-enhancing scans.
We do not know how many lesions the patients had prior to the study, but it is quite possible that many/most patients had lesions (since that is one of the tools used to dx MS.)
Although they failed to divulge all of the information as to lesion load etc at baseline, it doesn’t matter because there was NO change in new or newly enlarging lesions from baseline between the Tysabri group and the placebo group according to the findings from the more accurate Gd-enhancing scans.
One has to wonder why would a company withhold information when they proclaim a drug to have such a great effect? After all, they supposedly came to this conclusion of the drug being so beneficial from reviewing all the data, so the data should show the great effect as well.
Again, hopefully all the data will be released soon so that it can be peer reviewed. But so far, we have only seen what Bigoen has wanted us to see and when that happens, a lot of questions and uncertainty take place.