June: Unrelated Blogger Comments

Unrelated BLOGGER Comments

Sometimes you what to say something that is unrelated to the threads. This is a spot for You. 

You probably will not see you comment appear, please give it time it will appear eventually.

If you have 2 to 3 minutes to spare he would appreciate it if you could complete the following survey:
Internet Usage Survey


Anonymous said...
Not a comment but an important question, foremost to the research team in relation to the article posted on http://teachneuro.blogspot.de/2012/05/spurious-elevations-of-vitamin-b12-with.html

It is VERY likely that I am one of those people with thrice as high Vit B 12 levels than normal (blood tests for over 3 years). Nobody can explain why. From my own research I strongly suspect pernicious anemia because I've got 2 disorders linked to that (I also have iron deficiency which coincided with the onset of RRMS).

So my question is: which tests should I suggest to my GP next time I see him in order to know what's going on for sure? Since I've got more than one autoimmune disorder it is imperative to tackle a faulty Vit B metabolism, methinks.

Your thoughts on this would be GREATLY appreciated - I've hit a brick wall so far with my doctors.
Gavin Giovannoni said...
Re: "So my question is: which tests should I suggest to my GP next time I see him in order to know what's going on for sure? Since I've got more than one autoimmune disorder it is imperative to tackle a faulty Vit B metabolism, methinks."

I suggest you make your GP aware of the article in the NEJM and he/she should screen you for auto-antibodies associated with pernicious anaemia and/or do a Schilling's test. The latter is a specialised test done by haematologists to assess the absorption of vB12.

Please note this blog is not the forum for personal medical advice. So I can't give you anything more specific.
Anonymous said...
Dear Prof

thanks a lot, that's exactly what I needed to know - helps a lot. I apologize for this very me-centred question but I had no choice in this specific case.
Tony Fonda said...
Dear Gavin, Mouse,

I have a quick question that has been puzzling me lately.

I am trying to understand Pharma's marketing material.

When Company X says that its DMD Y cuts down on relapses by 50% per annum:

Does it mean that:

if 2 people with MS are taking this drug (1 relapse per person per year), one will relapse as usual and the other will not.

OR

the same 2 people (1 relapse per person per year), will have 0.5 relapse per year after taking the drug (i.e. a relapse every 2 years)?

In other words, I am wondering if the 50% relapse reduction rate is an average (or median) or a sum or positive/negative obs ?

Tony
MouseDoctor said...
Dear Tony

You personally can not have half a relapse (0.5) so in this case it would be one relapse every two years as you say

In terms of the 50% reduction in relapse rate, this means that you have half as many relapses as would occur if you were not having the drug.

So if the Annual relapse rate on drug was 0.25 compared to 0.5 on placebo. It means that on average people on placebo have one relapse every two years and the person on the drug had on average on relapse every 4 years. As you say this is an average so the middle mark and within any trial some people to better than the average and some people to worse.
Tony Fonda said...
Thanks Mouse.

But I must say that this does not really address my question.(probably because I didn't phrase it properly).

If you have 4 balls in a box, and you take 2 balls: you are left with 50% of the balls.

If you cut each of the 4 balls in half, you are left with 50% as well?

so what does 70% reduction on Tysabry mean? NO RELAPSE for some and full relapse for the rest, or reduction for all on an equal basis?

I logged a formal question to Biogen Idec (both USA and UK) this afternoon. Awaiting their replies (ought to come from the statisticians who analysed the data of the clinical trials...)
MouseDoctor said...
so what does 70% reduction on Tysabry mean? NO RELAPSE for some and full relapse for the rest, or reduction for all on an equal basis?

Yes, no relapse of full relapse there is nothing in between in this context. You have a relpse or you do not. There is nothing about a mild or severe relapse in this context

If you have a 70% reduction of relapse it means you are 70 percent less likely to have a relapse that would occur if you took nothing=placebo

So if 100 people were taking tysabri only 30 would relapse compared to a 100 taking placebo.

The beneficial effect is statisitical and not impirical and not on an equal basis

However if you relapsed does this means the drugs failed... well not necessarily as you may have been destined to have two or more relapese as the drug got rid of one or two etc. of them. Likewise it could be less severe than it would have been
Tony Fonda said...
Thanks again Mouse you're the best.

Let's wrap-up: I did not mean that you could have a partial (or light) relapse as it is an indivisible event. Either it happens or not.

But as you know, MS is a long term experiment.
You are answering me as if our horizon is 1-2 years. but how about 5-6 years? then no need to talk about decimals any more .

"If you have a 70% reduction of relapse it means you are 70 percent less likely to have a relapse that would occur if you took nothing=placebo

So if 100 people were taking tysabri only 30 would relapse compared to a 100 taking placebo."

Over a time frame of 5 years, does the above means that:

I) all tysabri takers will have a total reduction in relapses over 5 years of 70% - on an equal basis.

OR

II) some people will have a reduction of 100% and the others will relapse as frequently as needed to get to a population average of 70%?

This second scenario clearly excludes NABs, SPMS, drug holidays... as those extreme observations will render the average irrelevant.

again, I appreciate the technicalities of this question and will post if I ever hear back from the manufacturer.
MouseDoctor said...
The information comes from clinical trials these last no more than 3 years so there is no real answer for 5 years.
Tony Fonda said...
Can I conclude that 70% were relapse free during the 3 year time frame?

Any post-marketing study on these guys with a longer horizon?
Anonymous said...
i've always understood the relapse reduction to be an aggregate for all patients:

When there is a 70% relapse reduction with a drug
-some patients may have 0 relapses
-some may have fewer relapses
-a few may stay the same
-and a few may even get worse

The 70% is for the group as a whole. We need to know many were in each of the above categories. Perhaps half the patients fell in the 0 relapses category and 5% of the patients got worse
Tony Fonda said...
Precisely!

Neither you nor me are averages.

An average may work for a regulator, a manager or an investor.

But as we know, I am an individual and not an average.

The "look through" data analysis should be published if it has not already.... I wonder if there are statistical tables out there?
Tony Fonda said...
Biogen-Idec return to me after 48 hours with this answer:

"We investigated this situation for you and can tell you that Tysabri has cut ARR by 68%".

Then I called to understand more and was outraged by their reply:
"We can not and will not disclose any more information"

I calmly explained to them that this information is needed in my decision making as it is a matter of life or death - and asked them to provide me the info within the next 10 days or I will file a claim in the UK courts.

And I will. I am not playing poker games.

To be continued....
Roshni said...
Good! We should have complete information clearly laid out and I think treating neurologists need to have it. An average is not enough
MouseDoctor said...
You can read the actual figures in phase III trial the paper by Polman et al. As you will read it was based on a two year study.

http://www.nejm.org/doi/full/10.1056/NEJMoa044397

"After one year of treatment, natalizumab reduced the annualized rate of relapse to 0.26 relapse per year, as compared with 0.81 relapse per year in the placebo group (P<0.001) (Table 2). The 68 percent relative reduction in the annualized rate of relapse produced by natalizumab was maintained at two years (P<0.001)".

"The proportion of relapse-free patients was significantly higher in the natalizumab group than in the placebo group at one year (77 percent vs. 56 percent, P<0.001) and at two years (67 percent vs. 41 percent, P<0.001)".

If you are considering Tysabri please read the posts on PML.
MouseDoctor said...
The problem with post-marketing data is that there is no placebo arm and generally no natural history data.

Remember if you are thinking about Tysabri you need to know your JC virus status so taht you can asses the risks of taking the drug, which increase alot if you go past the 24 month period.

If you look at the Polman paper you can see the neurological landscape changing over time.
Roshni said...
That NEJM paper has all the figures
So the Biogen person who said 'we cannot and will not disclose ...' was very uninformed
Tony Fonda said...
Dear Mouse,

I have done good progress on this.

Caroline Wilding (head of the medical information distribution dept) reached out and agreed to share the post marketing data.

I am potentially looking at 6 years of history for up to 80,000 users.

That should allow us to cluster in subgroups to understand more how Tysabri affects different patient-types.

One hick: I am not a medical professional and not allowed to received the data directly.
Can you kindly reach out to Caroline requesting the tape? She agreed to provide it : caroline.wilding@biogenidec.com

I will happily run the stats in Matlab once I get the tape.

Thanks for your help.

Tony
Anonymous said...
Well done Tony!

We are the 99 percent!!!
MouseDoctor said...
Dear Tony
I suspect that I am not considered a medical professional either.

Write to Prof G
(g.giovannoni@qmul.ac.uk) with details of the conversation that you have had with Caroline including what she said she would supply and the details of what you have requested and a contact email.

I don't understand what you mean by tape and in terms of looking at subtypes. Tysabri is licenced for treatement of RRMS there is a study in progressive MS ongoing.

Labels: