I want to make one more post, then I'm going away again. This will comment on a couple of Harryz's posts. (And by the way, we all should thank him for the effort that he puts into this and probably other boards.)
First, the comment use of Tysabri in SPMS
I'm thinking that if your niece's MS is that aggressive, it is either PPMS or SPMS. If that's the case, then I doubt they would use Tysabri on her..
I am not a doctor so I cannot comment on whether it is possible to use Tysabri in PPMS or SPMS, however, Tysabri certainly seemed to work VERY well against the aggressive form of MS suffered by the 5 yr old little girl. Seehttp://www.thisisms.com/modules.php?nam ... opic&t=598
As a laymen, I will speculate that it may very well work on SPMS, but that the data are not yet sufficienly robust to make that claim in the drug's label. The companies have not yet tested the drug in full-fledged clinical trials on SPMS (the current trials were only on RRMS patients).
Furthermore, as Harryz correctly points out, whether it would be effective would certainly be something for the patient and physicians to judge and act upon.
Now, onto a statement that I feel must be challenged:
So do you see how the study was manipulated to show benefit according to their measurements of effect. Of course I wish people would pay more attention to the real issue here as they boldly state "The exact relationship between MRI findings and the clinical status of patients is unknown. Changes in lesion area often do not correlate with changes in disability progression." So what is the point in using this criteria to determine if a drug is going to have any effect on a MS patients life?!!
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.
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.
Third, the FDA and many physicians believe that MRI findings ARE clinically significant, its just tying them to disease progression that is unknown.
Now, a couple of comments on the 'basis' for the above 'manipulation' statement, which came from someone whom Harryz communicates with and is supposedly knowledgable about MS Research. I will quote from Harryz's post.
First of all the patients who were in Study 1 had a disease duration of 5 years versus the patients in Study 2 had a disease duration of 7 years and consequently the percentage of relapse change is significantly different between the two Studies. Furthermore, the patients in Study 1 which Biogen has been boasting that it showed a 66% decrease in relapse rate, most likely had a very low score on the EDSS because "approximately 94% had never been treated with these agents (interferons or copaxone)" but of course they don't bother to tell us what the median EDSS score was in this group. They only tell us that patients were enrolled that had an EDSS score between 0 and 5.0. Most likely the majority of these patients were closer to 0 given that 94% had never received any treatment. (My comment: I believe that Serono alluded to this lack of information in their recent press release on Tysabri.)
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.
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.
Next if you look at the tables in Figure 1 you will see that under MRI Endpoints it says that the median number of new or newly enlarging T2 lesions was 0.0 for the Tysabri group in Study 1 meaning that no new lesions were formed. Well since no new lesions were formed then that means that 60% of patients put in the Tysabri group never had any lesions to start with because it states that 60% of patients in the Tysabri group in Study 1 had no lesions.
I assume that the quote refers to Figure 1 (actually, Table 1) from the label information on Tysabri: http://www.tysabri.com/downloads/produc ... mation.pdf
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.
Second, note the Table 1 footnote, 'MRI endpoints by ordinal logistic regression adjusting for baseline lesion number.' 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.)
Third, the label did NOT state that 60% of patients had no lesions at the start of the study, it stated that 60% had no NEW lesions during the course of the study. There is a very important difference, and 60% of the Tysabri arm NOT developing new lesions verus 22% on placebo who did not develop new lesions certainly suggests Tysabri was effective in reducing lesion load (which was the study secondary endpoint).
I don't know how this can be viewed negatively, nor how the above supports the charge of 'manipulation.'
Readers might find it interesting to consider the definition of median. If the 'median' is 0, might there be some patients with reduced baseline lesion load? That is, not only no NEW lestions, but some of their study-start existing lesions were actually cleared. This is interesting, but I remind all that it is an ASSUMPTION.
Now more tell-tale is the Gd-enhancing lesions (active lesions) because the median in both the Tysabri group and the placebo group in Study 1 were 0.0, meaning no change from before they entered the study. This shows that 96% of the Tysabri group in Study 1 had no active lesions, but the placebo group had only 68% with no active lesions prior to the study. The Tysabri group had only 3% with 1 active lesion prior to the study, yet the placebo group had 13% with 1 active lesion prior to the study. The Tysabri group had only 1% with 2 or more active lesions prior to the study and the placebo group had 19% with 2 or more active lesions before the start of the study.
First, MRI endponits were adjusted for baseline lesion number. The statement that some had 'no active lesions prior to the study' cannot be made since we do not know what the baseline was. Indeed, all of the conclusions in the above quote are quite possibly based on a false premise, since we do NOT know the baseline lesion load ('lesions prior to the study.')
Again, how does this support any 'manipulation.'
Study 2 is just more of the same.
This dismissive tone is disappointing, but is suggestive of the author's bias.
I just don't agree with the 'manipulation' charge nor that the statements above support that charge. In sum,I don't know how the Tysabri trial results can be viewed negatively.
I hope these comments are useful and help to provide a different perspective on the Tysarbri results.