Re: st: pk analysis suite: elementary questions about -pkequiv-, -pkcross-, and -pkshape-

[Michael McCulloch <mm@pinestreetfoundation.org>]

Dear Joseph,
Thank you kindly for the very helpful response and example.
You write "the potential for carryover effects (by whatever name) to  
confound crossover studies
is often more serious with outcomes other than chemical  
concentrations." Might you be able to recommend some reading (either  
published or online tutorials) on this issue in crossover studies?
Best regards,
Michael McCulloch


On Feb 19, 2010, at 8:11 PM, Joseph Coveney wrote:

> Michael McCulloch wrote:
>
> I'm studying the manual (v11) for the pk suite, and have 3 questions:
> 1. Regarding the "carry" variable created by -pkshape-, in the manual
> example (p. 1325), is "carry" simply an indicator that shows whether
> or not a measurement was made in the same period/treatment
> combination, so that if
> 	"carry"==0, then no carryover is possible, and if
> 	"carry"==A, then a carryover effect is possible, but no evidence yet?
>
> 2. Can -pkcross- be used in to compare treatment response (e.g. pain
> score) in an AB-BA crossover study design, that was not a test of a
> biopharmaceutical drug concentration?
>
> 3. -pkequiv- performs bioequivalence tests using serum levels of
> biopharmaceutical drug concentration. Can the command also be used
> instead to measure *any* continuous outcome, measured following some
> other non-pharmaceutical intervention?
>
> --------------------------------------------------------------------------------
>
> 1.  Carryover is a term that indicates what the treatment (drug  
> formulation) was
> in the immediately preceding period.  Carryover is zero during the  
> first period;
> afterward (where the potential for carryover effects is of concern)  
> its pattern
> distinguishes between sequences of first-through-penultimate  
> treatments.  In the
> two-sequence, two-formulation, two-period crossover design (i.e., AB  
> BA), during
> the second period it is 1 for one of the treatments and 2 for the  
> other.  You
> can get a handle on what it does by inspecting the variables -treat-  
> and -carry-
> after running the do-file below.
>
> 2.  There's no reason why not.  As far as I'm aware, -pkcross- is  
> nothing but a
> convenience command that calls -anova- and displays the ANOVA table  
> in a format
> more familiar to biopharmaceutics scientists.  Crossover study  
> designs are not
> unique to pharmaceutical equivalence evaluation.  And although the  
> phenomenon is
> called "carryover" in biopharmaceutics, you will have the same  
> concern in other
> disciplines, namely, that the first exposure to a condition might  
> change things
> so that a second exposure will result in a different score ("learning
> phenomenon", "sensitization", "desensitization", "stimulus fatigue",  
> "acquired
> tolerance").
>
> 3.  Again, there is no reason not to:  the term *equivalence* has  
> more general
> usage than for drug concentrations in blood plasma.  Keep in mind  
> that the
> potential for carryover effects (by whatever name) to confound  
> crossover studies
> is often more serious with outcomes other than chemical  
> concentrations.  And it
> sometimes gets tricky even with the latter.
>
> Joseph Coveney
>
> clear *
> set more off
> set seed `=date("2010-02-20", "YMD")'
> input str1 trt
> "A"
> "B"
> "C"
> end
> tempfile tmpfil0
> save `tmpfil0'
> rename trt seq
> forvalues replicate = 1/2 {
>    cross using `tmpfil0'
>    replace seq = seq + trt
>    drop trt
> }
> erase `tmpfil0'
> generate byte id = 3
> expand id
> sort seq
> replace id = _n
> forvalues per = 1/3 {
>    generate byte period`per' = floor(runiform() * 100)
> }
> pkshape id seq period1 period2 period3
> sort id period
> order id sequence period treat carry outcome
> list, noobs sepby(id)
> exit
>
>
>
> *
> *   For searches and help try:
> *   http://www.stata.com/help.cgi?search
> *   http://www.stata.com/support/statalist/faq
> *   http://www.ats.ucla.edu/stat/stata/


Best wishes,

Michael McCulloch
Pine Street Foundation
124 Pine Street
San Anselmo, CA 94960-2674
tel:	415-407-1357
fax: 	206-338-2391

*
*   For searches and help try:
*   http://www.stata.com/help.cgi?search
*   http://www.stata.com/support/statalist/faq
*   http://www.ats.ucla.edu/stat/stata/