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From | "Joseph Coveney" <jcoveney@bigplanet.com> |
To | <statalist@hsphsun2.harvard.edu> |
Subject | Re: st: pk analysis suite: elementary questions about -pkequiv-, -pkcross-, and -pkshape- |
Date | Sat, 20 Feb 2010 13:11:26 +0900 |
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/