Data Abstraction Form for population PK, PD publications

Transcription

1 Data Abstracton Form for populaton PK/PD publcatons Brendel K. 1*, Dartos C. 2*, Comets E. 1, Lemenuel-Dot A. 3, Laffont C.M. 3, Lavelle C. 4, Grard P. 2, Mentré F. 1 1 INSERM U738, Pars, France 2 EA3738, Lyon, France 3 SERVIER, Courbevoe, France 4 EXPRIMO NV, Lumnen, Belgum * the two frst authors contrbuted equally to ths Data Abstracton Form 1

2 Table of contents Purpose(s) of modelng 3 Software 3 Method (If NONMEM software used) 4 Data (buldng dataset) 4 Structural model (based on) 5 Inter Indvdual Varablty model 6 Inter Occason Varablty model 6 Error model 7 Basc model selecton crtera 7 Covarate model 8 2

3 ARTICLE IDENTIFICATION DATE OF PUBLICATION (YEAR).... TITLE FIRST AUTHOR

4 Purpose(s) of modelng Descrptve Estmaton of PK and/or PD parameters Estmaton of parameters varablty Testng Covarate nfluence Other:.. Predctve Concentratons Effects (contnuous or dscrete) Tme to event Probablty Other: f predctve: Extrapolaton Interpolaton Defne:... Decson analyss Tral smulaton Method comparson Other: Software ADAPT Bugs, PKBugs or Wnbugs Knetca MP2 NONMEM NPML P-PHARM R (nlme) Splus (nlme) SAS (PROC NLMIXED) USC*PACK (NPEM) WnNonMx Other software:.. 4

5 Method (If NONMEM software used) FO FOCEI FOCE LAPLACIAN FOCE CENTERED HYBRID Other method :.. Molecule(s) ncluded n the model 1 Number:. Name(s): Data (buldng dataset) Number of subjects:.. f not reported, planned:... Number of observatons:. f not reported, planned:... Range of number of observatons per subject per dosng nterval? mn... max mean/med f not reported, planned:... In how many occasons has PK samplng been performed? mn... max...mean/med f not reported, planned:... Occasons taken nto account as dfferent ndvduals Number of subjects:.. f not reported, planned:... Number of observatons. f not reported, planned:... Range of number of observatons per subject per dosng nterval? mn... max mean/med f not reported, planned:... In how many occasons has PK samplng been performed? mn... max...mean/med f not reported, planned:... Occasons taken nto account as dfferent ndvduals Observaton types for PD: Contnuous Ordered categorcal Bnary Tme to event Non Ordered categorcal Count data 1 Internatonal Nonpropretary Names (=DCI) (f not publshed, company dentfcaton number) 5

6 Structural model (based on) (or for PKPD): 1 cpt. Frst order absorpton 2 cpts. Zero order absorpton 3 cpts. Other absorpton Nonlnear elmnaton Model for parent and metaboltes Jont model wth sequental ft Jont model wth smultaneous ft Separate Other: (or for PKPD): Lnear model Emax model Indrect model wth baselne wth gamma Physologcal model Effect compartment model Logstc model Log lnear model Ordered categorcal model Transton model (Markov) Tme to event model Count model Bndng model Model for parent and metaboltes effects Effect only functon of parent Effect only functon of metaboltes Effect functon of parent and metaboltes Other: For the PKPD study Sequental ft (fxng PK parameters to populaton estmates) Sequental ft (fxng PK parameters to ndvdual estmates) Smultaneous ft 6

7 Inter Indvdual Varablty model ( : Parameter typcal value, θ : Indvdual parameter, η : ndvdual random effects ) Addtve = + Exponental = exp None Multplcatve = (1+ η ) Non parametrc Other:.. Inter ndvdual varance-covarance matrx dagonal / non dagonal Addtve = + Exponental = exp None Multplcatve = (1+ η ) Non parametrc Other:.. Inter ndvdual varance-covarance matrx dagonal / non dagonal Inter Occason Varablty model None Number of occasons:.. Inter occason varance-covarance matrx dagonal / non dagonal None Number of occasons:.. Inter occason varance-covarance matrx dagonal / non dagonal 7

8 Error model (OBS j : Observatons, IPRED j : Indvdual Predcton, ε j : resdual error) Log transformed data Transformed both sdes (log-log) Addtve OBS j =IPRED j + ε j Multplcatve OBS j =IPRED j (1+ ε j ) Combned OBS j =IPRED j (1+ ε1 j )+ ε2 j Other:.. Log transformed data Transformed both sdes (log-log) Addtve OBS j =IPRED j + ε j Multplcatve OBS j =IPRED j (1+ ε j ) Combned OBS j =IPRED j (1+ ε1 j )+ ε2 j Other:.. Basc model selecton crtera No buldng steps Wald test Graphs Akake Crteron, Bayesan nformaton crtera (or SC), Lkelhood, Objectve functon Lkelhood Rato Test p value not adjusted p adjusted usng an arbtrary crteron p adjusted usng multple test theory Randomsaton test Resduals dstrbuton Other: 8

9 No buldng steps Wald test Graphs Akake Crteron, Bayesan nformaton crtera (or SC), Lkelhood, Objectve functon Lkelhood Rato Test p value not adjusted p adjusted usng an arbtrary crteron p adjusted usng multple test theory Randomsaton test Resduals dstrbuton Other: Covarate model No covarate model Covarate test Whch covarate has been tested?...or..kept n fnal model? Heght Weght BMI Demographc factors Bology Age Gender BSA Ethnc factor Creatnne clearance Serum Creatnne Hepatc markers (AST, ALT, blrubn...) Genotype / Phenotype (Metabolsm) 9

10 Other(s):. Number of covarates tested? Number of covarates n the fnal model?. Covarate selecton based on post-hoc Performed Not performed Graphs GAM (or bootstrap of GAM) Trees Unvarate tests Other:. Covarate populaton model buldng Forward Backward Stepwse (forward and backward) Crtera used for covarate model buldng Wald test Akake Crteron, Bayesan nformaton crtera (or SC), Lkelhood or objectve functon Decrease IIV of a parameters predcton Decrease SE of fxed effect Clncal relevance Lkelhood Rato Test p value not adjusted p adjusted usng an arbtrary crteron p adjusted usng multple test theory Randomsaton test Other:. 10

11 No covarate model Covarate test Whch covarate has been tested?...or..kept n fnal model? Heght Weght BMI Demographc factors Age Gender BSA Ethnc factor Creatnne clearance Serum Creatnne Bology Hepatc markers (AST, ALT, blrubn...) Genotype / Phenotype (Metabolsm) Other(s):. Number of covarates tested? Number of covarates n the fnal model?. 11

12 Covarate selecton based on post-hoc Performed Not performed Graphs GAM (or bootstrap of GAM) Trees Unvarate tests Other:. Covarate populaton model buldng Forward Backward Stepwse (forward and backward) Crtera used for covarate model buldng Wald test Akake Crteron, Bayesan nformaton crtera (or SC), Lkelhood or objectve functon Decrease IIV of a parameters predcton Decrease SE of fxed effect Clncal relevance Lkelhood Rato Test p value not adjusted p adjusted usng a arbtrary crteron p adjusted usng a multple test theory Randomsaton test Other:. 12