# PharmPK Discussion - Difference between PK cycles

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• On 22 Jul 2003 at 10:39:49, Rostam Namdari (chista90.-a-.yahoo.com) sent the message
`The following message was posted to: PharmPKDear Colleagues,For comparing PK parameters between two cycles weproposed to look at the 95% confidence intervalsassociated with the least square geometric mean (LSGM)for the Cl, AUC, MRT and Vss and if contained thevalue of 1 then conclude no statistically significantdifference.  Do we need to declare the width of the CIfirst and if the CI falls within that declaredinterval, then conclude that the two Cycles areequivalent.  What should be the width (80%-125% orothers)? Is it necessary to include 1.0 in theinterval?  What about just looking at p-values?Rostam`
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• On 22 Jul 2003 at 15:48:08, "Bonate, Peter" (pbonate.-a-.ilexonc.com) sent the message
`The following message was posted to: PharmPKDear Rostam,You asked the following:For comparing PK parameters between two cycles we proposed to look atthe 95% confidence intervals associated with the least square geometricmean (LSGM) for the Cl, AUC, MRT and Vss and if contained the value of1 then conclude no statistically significant difference.  Do we need todeclare the width of the CI first and if the CI falls within thatdeclared interval, then conclude that the two Cycles are equivalent.What should be the width (80%-125% or others)? Is it necessary toinclude 1.0 in the interval?  What about just looking at p-values?I would not look at p-values because these are meaningless.  First,they test the hypothesis that the means are different.  This is a sillynull hypothesis because of course they will be different.  The questionis, are they clinically or meaningfully different.  For that you need aconfidence interval approach.  That is the rationale for the whole CIapproach in bioequivalence.  Looking only at whether the CI contains 1is not very informative either and can be quite misleading.  Supposeyour CI is 0.1 to 10.  This interval does contain 1, but obviously thestandard error of the mean is so large that the estimate is veryimprecise.  This might happen if the sample size is small.  So, yes, Iwould a priori define a acceptance interval that if my entire CI iscontained within I would declare the two means to be equivalent.I would just use what some of the guidance's recommend: 90% CIcontained within 80 to 125% or 70 to 143%, depending on the therapeuticwindow of the drug.  If you don't know what the window is go with 80 to125%.Good luck,Peter Bonate`
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• On 23 Jul 2003 at 07:35:08, Priti Pandey (priti_pandey.at.yahoo.com) sent the message
`Dear Mr. Rostam Namdari,If you are going for95% CI calculation then you need to write range(orwidth)of your CI, means upper limit and lower limit of interval and ifinterval include 1 mean there is no statistically significantdifference and if 1 comes in between your interval then definitely youhave to include that. I don’t have idea about what should be the widthof interval (it again depends upon regulatory agency) . If you look foronly "p" value means you will get only conclusion about, “Is there anysignificant difference between two cycle or not?” But when you look forCI means you will evaluate spread of your observation around your meanvalue and can evaluate strength of significance also. From CI, you canevaluate how much variation is there in your observation.RegardsPritiBiostatisticianAurobindo Pharma, Hyderabad, India`
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