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From: Fisher Dennis <fisher_at_PLessThan.com>

Date: Thu, 10 Dec 2015 08:23:56 -0800

Colleagues

I have fit an exposure response model using NONMEM — the optimal =

model is a segmented two-part regression with Cp on the x-axis and =

response on the y-axis. The two regression lines intercept at the =

cutpoint.

The parameters are:

slope of the left regression

cutpoint between regressions

“intercept” — y value at the cutpoint

slope of the right regression (fixed at zero; models in which =

the value was estimated yielded similar values for the objective =

function)

I have been asked to calculate the confidence interval for the response =

at various Cp values.

Above the cutpoint, this seems straightforward:

a. if NONMEM yielded standard errors, the only relevant =

parameter is the y value at the cutpoint and its standard error

b. if NONMEM did not yield standard errors, the confidence =

interval could come from either likelihood profiles or bootstrap

My concern is calculating at Cp values below the cutpoint, for which =

both slope and intercept come into play. Any thoughts as to how to do =

this in the presence or absence of NONMEM standard errors?

The reason that I mention with / without presence of SE’s is =

that this model was fit to two different datasets, one of which yielded =

SE’s, the other not.

Any thoughts on this would be appreciated.

Dennis

Dennis Fisher MD

P < (The "P Less Than" Company)

Phone: 1-866-PLessThan (1-866-753-7784)

Fax: 1-866-PLessThan (1-866-753-7784)

www.PLessThan.com <http://www.plessthan.com/>

Received on Thu Dec 10 2015 - 11:23:56 EST

Date: Thu, 10 Dec 2015 08:23:56 -0800

Colleagues

I have fit an exposure response model using NONMEM — the optimal =

model is a segmented two-part regression with Cp on the x-axis and =

response on the y-axis. The two regression lines intercept at the =

cutpoint.

The parameters are:

slope of the left regression

cutpoint between regressions

“intercept” — y value at the cutpoint

slope of the right regression (fixed at zero; models in which =

the value was estimated yielded similar values for the objective =

function)

I have been asked to calculate the confidence interval for the response =

at various Cp values.

Above the cutpoint, this seems straightforward:

a. if NONMEM yielded standard errors, the only relevant =

parameter is the y value at the cutpoint and its standard error

b. if NONMEM did not yield standard errors, the confidence =

interval could come from either likelihood profiles or bootstrap

My concern is calculating at Cp values below the cutpoint, for which =

both slope and intercept come into play. Any thoughts as to how to do =

this in the presence or absence of NONMEM standard errors?

The reason that I mention with / without presence of SE’s is =

that this model was fit to two different datasets, one of which yielded =

SE’s, the other not.

Any thoughts on this would be appreciated.

Dennis

Dennis Fisher MD

P < (The "P Less Than" Company)

Phone: 1-866-PLessThan (1-866-753-7784)

Fax: 1-866-PLessThan (1-866-753-7784)

www.PLessThan.com <http://www.plessthan.com/>

Received on Thu Dec 10 2015 - 11:23:56 EST