- On 1 Mar 2013 at 18:55:47, Yi Gu (gooey1981.aaa.yahoo.com.cn) sent the message

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Hi there,

I like to ask a stupid question. I saw the plots of theraputic frequency

(such as frequency of ineffective therapy, effective therapy, minor AE and severe Tox) vs systemic exposures in some Clin Pharm books or papers. These plots show continuous curves. I did not understand how they were generated. Almost no book tells how to draw it, but just presents it.

I understand the plots of therapeutic frequency vs dose levels. These plots are histograms, separated by the dose levels. It is understandable

that for each dose level, we can calculate the probability of the patient number showing response in each dose levels. And dose level, here, can be regarded as catagory variable.

But for the plots of theraputic frequency vs syetemic exposures, as systemic exposure is continuous variable, how to calculate the the probability of the patient number at each exposure to generate those continuous curves?

Hope my question is clear.

Thanks

Yi - On 2 Mar 2013 at 18:32:00, Joachim Grevel (jgrevel.aaa.btconnect.com) sent the message

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The following message was posted to: PharmPK

Dear Yi,

What you see in text books are often "picture models", and there is no clear

mathematical-statistical function behind them. I have, however, generated

continuous curves that show how the hazard of a certain event changes with

exposure. Now, that change in hazard is continuous, and it is backed up by a

parametric hazard function. You get the probability of the event by integrating

the hazard function.

As always, the "stupid" questions are the interesting ones.

Good luck,

Joachim

Joachim Grevel, PhD

Scientific Director

BAST Inc Limited

Loughborough Innovation Centre

Charnwood Building

Holywell Park, Ashby Road

Loughborough, LE11 3AQ - On 3 Mar 2013 at 10:31:02, Yi Gu (gooey1981.aaa.yahoo.com.cn) sent the message

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The following message was posted to: PharmPK

Dear Joachim,

I seems to have get some ideas. It is necessary to set up a model

linking the probability to the exposure, then the plot shows the model

fitting curve. Am I right?

Can you recommend any reference related to this modeling and plotting

process?

Many thanks.

Sincerely,

Yi - On 3 Mar 2013 at 08:29:10, Joachim Grevel (jgrevel.aaa.btconnect.com) sent the message

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The following message was posted to: PharmPK

Dear Yi,

It was Nick Holford who taught us pharmacometricians the art of

"time-to-event analysis". Google him with that phrase and you will find

his

excellent lectures.

Happy discovery,

Joachim

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