Vaccine Analysis. What is a 4-fold increase?

[dave]

I thought I knew what a 4-fold increase was untill I was asked to find
a reference/definition!

Some background to the problem. Patients have their baseline antigen
level recorded, they are then given a dose of a vaccine, and have their
antigen level recorded 4 weeks later.

My thinking is if a patient has a baseline level of 5, and a
post-baseline level of 20 then this is a an example of a 4-fold
increase (5x4=20, or 20/5=4).

However, it has been pointed out to me that if the same patient has a
post-baseline level of 5 then this (under my definition) is a 1-fold
increase (5x1=5, or 5/5=1)?

How can a 1-fold increase, not be an increase at all? And is a 0.5-fold
increase a decrease (5x0.5=2.5, or 2.5/5=0.5)????

I have used this definition of a 4-fold increase before, but cannot
find a definition anywhere. Does anybody know where I might find a
definition of a 4(or any)-fold increase?

Many thanks

Dave

[John Whittington]

At 01:29 14/04/05 -0700, dave wrote (in part):

>I thought I knew what a 4-fold increase was untill I was asked to find
>a reference/definition!

>....

>My thinking is if a patient has a baseline level of 5, and a
>post-baseline level of 20 then this is a an example of a 4-fold
>increase (5x4=20, or 20/5=4).
>However, it has been pointed out to me that if the same patient has a
>post-baseline level of 5 then this (under my definition) is a 1-fold
>increase (5x1=5, or 5/5=1)?

My tuppence worth ....

Ah - an 'old faithful' issue - I guess essentially an issue of 'semantic
conventions'! My personal belief is that one should always simply say
'what one means', in simple unambiguous language; in this case maybe that
would mean talking in terms of something like 'antigen level ratio'. What
follows is 'my view', which other may contest! ....

I'm not sure that the x-fold terminology necessarily presents too much of a
consistency problem. If one accepts (as per your initial thinking) that
the x-fold terminology is (certainly in the eyes of the world at large),
about multiplicative changes in figures, is not a '1-fold increase' not a
reasonable expression of 'no change', just as would be a 'zero increase' if
we were talking about an additive descriptor? Similarly, for a
multiplicative descriptor, I do think that (messy though it is) a 0.5-fold
increase reasonably describes a halving, just as 'an increase of -6'
reasonably describes a reduction of 6.

The problem obviously relates to whether one is talking/thinking of a
'4-fold increase' ('an increase TO 4-fold') or 'an increase OF 4-fold'
(which would technically mean an 'increase TO 5 fold') - but I think that,
like you, almost everyone would take the former view.

In terms of percentages, the opposite seems to apply (except in the hands
of the media, government and other abusers of statistics!). A '100%
increase' fairly obviously means a doubling (2-fold increase), hence a
'200% increase' means an increase from 100% to 300% (3-fold increase)
etc. However, one has to be careful to look at the words, since an
increase 'TO 200%' (rather than 'OF 200%) is presumably a '100% increase'
('increase OF 100%', '2-fold increase').

It's when people (often the media) start talking about x-fold decreases
(decreases of x%, where x>100!) when the real problems start!

That's how I see it, anyway - I wonder about others!

Kind Regards,


John

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[Ted Harding]

I doubt you can find a formal definition of "X-fold increase"
anywhere. It's not really formal language, even though the
normal usage will be quite clear and definite. People will
read this as "X is the factor by which you multiply the original
value to get the final value", in the normal interpretation of
language (just as you have done).

But the operative word, in normal usage, is "increase". Hence
"4-fold increase", "50% increase", and so on.

Likewise "4-fold decrease" and so on, whereby you *divide* by
the factor X (though this is not quite so obvious, perhaps).

One would not normally use, I think, "1-fold increase" (any
more than "1-fold decrease"), especially as this might mislead
people into inferring that there had been a positive increase
(by an amount equal to the original, perhaps).

So I'd suggest that it's best to confine such usage to
statements where the meaning is obvious and natural, and
treat questions like "Well, what's a 1-fold increase, then?"
as nit-picking which is out of place in such usage.

If you really are in a situation where things may go up,
or down, or remain unchanged, then I'd feel inclined to
avoid such language altogether and instead something like
"changed by a factor of X" where X could be 4, 1/4, or even 1!

Hoping this helps,
Ted.


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E-Mail: (Ted Harding) <Ted.H...@nessie.mcc.ac.uk>
Fax-to-email: +44 (0)870 094 0861
Date: 14-Apr-05 Time: 10:37:51
------------------------------ XFMail ------------------------------

[Gunter...@csl.com.au]

A4-fold increase in antibody levels is one of the CPMP criteria for evaluating Flu vaccines. Going from a pre-vaccination titre of 10 to a post-vaccination titre of 40 or more qualifies as a 4-fold increase. If you log transform your data first then fold-increases are natural to evaluate - simply take the antilog of the differences, etc.
Cheers


________________________________

From: dave [mailto:dave_...@yahoo.co.uk]
Sent: Thu 04/14/05 18:29
To: MedS...@googlegroups.com
Subject: MEDSTATS: Vaccine Analysis. What is a 4-fold increase?




I thought I knew what a 4-fold increase was untill I was asked to find
a reference/definition!

Some background to the problem. Patients have their baseline antigen
level recorded, they are then given a dose of a vaccine, and have their
antigen level recorded 4 weeks later.

My thinking is if a patient has a baseline level of 5, and a
post-baseline level of 20 then this is a an example of a 4-fold
increase (5x4=20, or 20/5=4).

However, it has been pointed out to me that if the same patient has a
post-baseline level of 5 then this (under my definition) is a 1-fold
increase (5x1=5, or 5/5=1)?

How can a 1-fold increase, not be an increase at all? And is a 0.5-fold
increase a decrease (5x0.5=2.5, or 2.5/5=0.5)????

I have used this definition of a 4-fold increase before, but cannot
find a definition anywhere. Does anybody know where I might find a
definition of a 4(or any)-fold increase?

Many thanks

Dave





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