On the "old" BT forum, Mark looked at the CRAB stats and compared them with what Biogen has been touting with Tysabri. He came up with a number that said Tysabri was only about 12% more effective than the CRABs.

Now after reading this article comparing relative and absolute numbers, does anyone really think that Biogen is being truthful about the efficacy of Tysabri?

Harry

I'm not so sure it is a matter of being truthful, Harry, as the stats that are reported are accurate.

It is more a matter of what numbers are more relevant to us as consumers.

At a minimum, I want to know the average number of people who benefited, over & above the ones that saw just as much benefit by using placebo.

What they are presenting though, is a number relative to those on placebo. So, if placebo reduced relapses by 20%, and the drug reduced relapses by 30%, they advertise this as a 50% improvement [B].

30% - 20% = 10% --> 10%/20% = 50% improvement . . . wow!

People misunderstand this to mean that there IS a 50% improvement over using nothing.

The bottom line is that only 10% of the people did better then those on placebo or nothing, right?

But, many would argue "this is the way it is done".

Cherie

Absolutely BBS, and I am still on Paxil and have been for about 6 yrs, and it's saved my sanity. But, I am on the highest dose recommended and it's losing it's effectiveness for me, and I may have to replace it with another AD?

If I had known the truth about Paxil from the beginning, I may or may not have chosen to take it. I should have been given that choice and not hoodwinked into believing otherwise.

Actually I tried Prozac first, but it made my anxiety worse. It was like taking an upper. ...For Me!

Hi Harry,

That's not what I said (sorry). I just quoted the AFFIRM Tysabri monotherapy trial results, which found a relative risk reduction of disability progression of about 43% but an absolute risk reduction of 12% (29% placebo vs. 17% on Tysabri, or a difference of 12%).

By contrast, the phase III Avonex trial found a relative risk reduction of disability progression of about 37%, but an absolute risk reduction of 13% (35% placebo vs. 22% Avonex).

So in a two year period, the number of people who would not suffer disability progression as a result of Tysabri or Avonex, is about the same, based on these trial results.

Mark

Just trying to understand this... How is the relative risk reduction of disability progression calculated?

Why is the placebo absolute risk reduction higher than the drug? How is it calculated?

Hi Mark,

Sorry for the lack of recollection memory Your comparison, IMHO, vs placebo improvement even makes Tysabri less of the blockbuster that Biogen has been preaching.

I still have a "feeling" that there are going to be some unexpected problems with the user group of this drug once the numbers start to increase.

Harry

If you read the link below, it explains it pretty clearly. Much better than I could do.

http://www.slate.com/id/2150354

Cherie,

Unfortunately most drug companies don't report their trial data in the manner that you would like to see. It is reported from the marketing/sales point of view because, as we know, that sells drugs!

And with a disease like MS, impressive advertised numbers will attract a lot of attention.

Harry

Yes Harry, that was my point. On the most important measure of effectiveness -- impact on disability -- Tysabri was no more effective than Avonex.

Tysabri fared better on other less important measures of effectiveness.

Mark

This is what this from Ectrims seems to be saying too:

Assessing the net clinical benefit and absolute risk reduction of disease-modifying drugs in relapsing-remitting multiple sclerosis

V. Samuel, K. Akhras, R. Bennett, R. Glanzman, A. AL-Sabbagh (Detroit, Rockland, New York, USA)

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Background: Clinicians and payers tend to compare the results of individual clinical trials utilizing relative risk reduction (RRR) for each disease modifying drug (DMD); however, inter-study variability, heterogeneity of the patient population, different baseline characteristics, and inconsistent placebo behaviors from different clinical trials makes comparison based on RRR inappropriate. Measurement of absolute risk reduction (ARR) may be a more appropriate assessment of benefit.

Objective: To compare baseline disease severity levels and ARRs across Class 1 DMD studies for multiple sclerosis.

Methods: Class 1 studies of various DMDs were reviewed and analyzed to compare baseline Expanded Disability Status Scale (EDSS) scores and relapse rates across DMD study populations. The clinical benefit of DMDs versus placebo for 2-year relapse rates and proportion of progression-free patients was compared across all studies using ARR and number needed to treat (NNT).

Results: The proportion of patients with 2, 3, or >=4 relapses at baseline for subcutaneous (sc) interferon-beta (IFNB)-1a treated patients were 41%, 33%, and 26% respectively. For natalizumab-treated patients, the proportion of patients with 1, 2, or >=3 relapses at baseline were 58%, 32%, and 9%, respectively with no reported data for intramuscular (im) IFNB-1a, IFNB-1b, and glatiramer acetate (GA).

The proportion of patients with baseline EDSS scores of >=3 was greater among IFNB-1a sc-treated patients compared with IFNB-1a im and natalizumab (41%, 33% [1], and 33%, respectively), with no reported data for IFNB-1b or GA. The ARRs for annualized relapse rates were 0.15, 0.24, 0.40, 0.41, and 0.45 for IFNB-1a im, GA, IFNB-1b, IFNB-1a sc, and natalizumab respectively (NNTs: 6.7, 4.2, 2.5, 2.4, 2.2). ARRs for progression-free patients were 0.13 [2], 0.03, 0.08, 0.12, and 0.12 for IFNB-1a im, GA, IFNB-1b, IFNB-1a sc, and natalizumab respectively (NNTs: 7.7 [2], 33.3, 12.5, 8.7, 8.7).

Conclusion: Given the difference in baseline risk and severity levels across studies, ARR is the appropriate way to compare DMDs in the absence of head-to-head clinical trials. Results based on ARR showed that IFNB-1a sc has comparable therapeutic effect on efficacy measures when compared to natalizumab.

1. Estimated from distribution of Baseline EDSS figure in the Clinical Review section (page 28) of Summary Basis of Approval for IFNB-1a im.
2. Apply to subset of patients (57%) who completed 2-year data.

http://registration.akm.ch/einsicht....NMASKEN_ID=900