Markov model dataset

Dear all, I am currently trying to model the transitions from CTCAE grade 0 - 3 (4 states) for several toxicities using a markov approach in Nonmem. However, I am facing some problems with the data set, which I cannot solve by myself. The set looks like this: C ID TIME DOSE DV EVID CMT AMT MDV 0 1 0 0 0 1 1 1 1 0 1 1 50 1 0 1 0 0 0 1 1 50 0 2 -1 0 1 0 1 1 50 0 2 -2 0 1 0 1 1 50 0 2 -3 0 1 0 1 1 50 0 2 -4 0 1 0 1 1 50 0 1 1 1 1 0 1 1 50 0 2 2 0 1 0 1 1 50 0 2 3 0 1 0 1 1 50 0 2 4 0 1 To implement the markov property the compartments are emptied and initialized after each observation. When I try to execute the model I get the following error message for every record where the compartment without a previous observation is emptied : COMPARTMENT ASSOCIATED WITH THE PREDICTION IS OFF In the example above this error refers to record 4 - 6. When I remove these records the model works, but then I am violating the markovian assumption, if I am not mistaken. Am I missing something important? Any help is highly appreciated! Here are the relevant parts of the control file: $DES K01_F = K01 * EXP(-GAM*T) + DOSE*SLP K02_F = K02 * EXP(-GAM*T) + DOSE*SLP K03_F = K03 * EXP(-GAM*T) + DOSE*SLP K12_F = K12 * EXP(-GAM*T) + DOSE*SLP K23_F = K23 * EXP(-GAM*T) + DOSE*SLP KB10 = KB * EXP(-BA*DOSE) KB21 = KB * EXP(-BA*DOSE) KB32 = KB * EXP(-BA*DOSE) KB20 = KB * EXP(-BA*DOSE) KB30 = KB * EXP(-BA*DOSE) DADT(1) = A(2)*KB10 + A(3)*KB20 + A(4)*KB30 - A(1) * (K01_F + K02_F + K03_F) ; No grade DADT(2) = A(1)*K01_F - A(2) * (K12_F + KB10) ; Grade 1 DADT(3) = A(2)*K12_F + A(1)*K02_F - A(3) * (K23_F + KB21 + KB20) ; Grade 2 DADT(4) = A(3)*K23_F + A(1)*K03_F - A(4) * (KB32 + KB30) ; Grade 3 $ERROR PB0 = A(1) PB1 = A(2) PB2 = A(3) PB3 = A(4) Y = 1 IF(DV.EQ.1.AND.CMT.EQ.1) Y = A(1) IF(DV.EQ.1.AND.CMT.EQ.2) Y = A(2) IF(DV.EQ.1.AND.CMT.EQ.3) Y = A(3) IF(DV.EQ.1.AND.CMT.EQ.4) Y = A(4) $ESTIMATION SIG=3 MAXEVAL=9999 PRINT=1 METHOD=1 LAPLACIAN LIKE NOABORT Thank you very much in advance! Kind regards ____________________ Achim Fritsch Pharmacist Klinische Pharmazie Pharmazeutisches Institut Universität Bonn An der Immenburg 4 53121 Bonn Tel.: 0228 / 73 5229 Fax.: 0228 / 73 9757 [email protected]