[R] Not sure this is something R could do but it feels like it should be.

Calum Polwart cpolwart at chemo.org.uk
Sun Jun 9 15:14:33 CEST 2013

>> Calum
> Hi Calum,
> I can only answer from the perspective of someone who calculated
> doses of alcohol for experimental subjects many years ago. It was not
> possible to apply a linear function across the range due to a number
> of factors. One is that BAC, which was the target value, is dependent
> upon the proportion of the weight that represents the water
> compartment of the body. This varies with both weight (heavier people
> typically have a higher proportion of fat) and sex (women also tend 
> to
> have slightly more fat). The real monkey wrench in the works was
> absorption rate, which often made nonsense of my calculations. This
> may not be as important in therapeutic drugs, for we were aiming at a
> specified BAC at a certain time after dosing rather than an average
> level.

All those things affect therapeutic dosing.

I may have oversimplified what we are trying to achieve to avoid 
getting bogged down in the detail of what we are trying to achieve and 
provide something people might be able to relate to.

However, we can assume that they are already sorted out, so we know the 
theoretically know what the 'correct' dose is for a patient.  The hard 
bit is unless you want to give everyone liquid so you can measure any 
dose possible you have to have a dose that is a multiple of something 
(Amoxicillin doses in adults are multiples of 250 because thats the size 
of the capsule).

What we are trying to do is determine the most appropriate number to 
make the capsules.  (Our dosing is more complex but lets stick to 
something simple.  I can safely assure you that vritually no-one 
actually needs 250 or 500mg as a dose of amoxicillin... ...thats just a 
dose to get them into a therapeutic window, and I'm 99% certain 250 and 
500 are used coz they are round numbers.  if 337.5 more reliably got 
everyone in the window without kicking anyone out the window that'd be a 
better dose to use!  So... what I'm looking to do is model the 
'theoretical dose required' (which we know) and the dose delivered using 
several starting points to get the 'best fit'.  We know they need to be 
within 7% of each other, but if one starting point can get 85% of doses 
within 5% we think that might be better than one that only gets 50% 
within 5%.

> However, I suspect that many therapeutic drugs have a different
> dose by weight for children (we weren't dosing children) and choosing
> a starting point at the bottom of the range would almost certainly
> introduce a systematic error. My intuition would be to anchor the
> dosage rate in the middle of the scale and then extrapolate in both
> directions (adults only, of course).

We are actually using a starting point that may be middle and going up 
and down if need be.

I think what we may want to do is run a loop through each weight (in 
1kg increments) and calculate their theoretical dose, and the dose for 
each possible starting point (there are certain contraints on that 
already so there may only be 20 possible start points), then we 
calculate the % variance for each dose to theoretical dose and calculate 
the Area Under & Above (some will be negative) the curve and the one 
that has the lowest AUC is then the one that most "precisely" will dose 
the patient...?

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