NM7 question

From: owner-nmusers Behalf Of Nick Holford Sent: Wednesday, November 04, 2009 6:43 PM To: nmusers Subject: Re: [NMusers] advan8 vs. advan13 (CORRECTION) Hi, Thanks to Peiming Ma and Thuy Vu for pointing out an error in my attempt to transform bioavailability into its logit. The logit transformation of a probability is ln(P/(1-P)) i.e. the log of the odds ratio. The reverse transform is correct i.e. exp(logit) is the odds ratio and P is then OR/(1+OR) (or 1/1+exp(-logit)). If THETA(1) is the bioavailability then this is (I hope) the correct transformation of THETA(1) and reverse transform to get the individual bioavailability with a random effect constrained to be within 0 and 1. MU_1=LOG(THETA(1)/(1-THETA(1)) ; logit of population bioavailability EXPP=MU_1+ETA(1) ; add random effect BIO=1/(1+EXP(-EXP(EXPP))) ; individual bioavailability Nick -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: n.holford http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

________________________________ From: owner-nmusers On Behalf Of Sam Liao Sent: Wednesday, November 04, 2009 7:31 PM To: 'nmusers' Subject: [NMusers] NM7 question Dear NONMEM team: To run the M3 method to handle BQL samples, we have to use method=LAPLACIAN NUMERICAL SLOW in NM6. Can we use the new methods in NM7 such as IMP, SAEM or BAYES if we have to run the M3 method? Best regards, Sam Liao Pharmax Reseach From: owner-nmusers On Behalf Of Nick Holford Sent: Wednesday, November 04, 2009 6:43 PM To: nmusers Subject: Re: [NMusers] advan8 vs. advan13 (CORRECTION) Hi, Thanks to Peiming Ma and Thuy Vu for pointing out an error in my attempt to transform bioavailability into its logit. The logit transformation of a probability is ln(P/(1-P)) i.e. the log of the odds ratio. The reverse transform is correct i.e. exp(logit) is the odds ratio and P is then OR/(1+OR) (or 1/1+exp(-logit)). If THETA(1) is the bioavailability then this is (I hope) the correct transformation of THETA(1) and reverse transform to get the individual bioavailability with a random effect constrained to be within 0 and 1. MU_1=LOG(THETA(1)/(1-THETA(1)) ; logit of population bioavailability EXPP=MU_1+ETA(1) ; add random effect BIO=1/(1+EXP(-EXP(EXPP))) ; individual bioavailability Nick -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: n.holford http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

From: [email protected] [mailto:[email protected]] On Behalf Of Nick Holford Sent: Wednesday, November 04, 2009 6:43 PM To: nmusers Subject: Re: [NMusers] advan8 vs. advan13 (CORRECTION) Hi, Thanks to Peiming Ma and Thuy Vu for pointing out an error in my attempt to transform bioavailability into its logit. The logit transformation of a probability is ln(P/(1-P)) i.e. the log of the odds ratio. The reverse transform is correct i.e. exp(logit) is the odds ratio and P is then OR/(1+OR) (or 1/1+exp(-logit)). If THETA(1) is the bioavailability then this is (I hope) the correct transformation of THETA(1) and reverse transform to get the individual bioavailability with a random effect constrained to be within 0 and 1. MU_1=LOG(THETA(1)/(1-THETA(1)) ; logit of population bioavailability EXPP=MU_1+ETA(1) ; add random effect BIO=1/(1+EXP(-EXP(EXPP))) ; individual bioavailability Nick -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

________________________________ From: [email protected] [mailto:[email protected]] On Behalf Of Sam Liao Sent: Wednesday, November 04, 2009 7:31 PM To: 'nmusers' Subject: [NMusers] NM7 question Dear NONMEM team: To run the M3 method to handle BQL samples, we have to use method=LAPLACIAN NUMERICAL SLOW in NM6. Can we use the new methods in NM7 such as IMP, SAEM or BAYES if we have to run the M3 method? Best regards, Sam Liao Pharmax Reseach From: [email protected] [mailto:[email protected]] On Behalf Of Nick Holford Sent: Wednesday, November 04, 2009 6:43 PM To: nmusers Subject: Re: [NMusers] advan8 vs. advan13 (CORRECTION) Hi, Thanks to Peiming Ma and Thuy Vu for pointing out an error in my attempt to transform bioavailability into its logit. The logit transformation of a probability is ln(P/(1-P)) i.e. the log of the odds ratio. The reverse transform is correct i.e. exp(logit) is the odds ratio and P is then OR/(1+OR) (or 1/1+exp(-logit)). If THETA(1) is the bioavailability then this is (I hope) the correct transformation of THETA(1) and reverse transform to get the individual bioavailability with a random effect constrained to be within 0 and 1. MU_1=LOG(THETA(1)/(1-THETA(1)) ; logit of population bioavailability EXPP=MU_1+ETA(1) ; add random effect BIO=1/(1+EXP(-EXP(EXPP))) ; individual bioavailability Nick -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford