Updated TGI models

DESCRIPTION

@@ -12,7 +12,8 @@ Description: A model library for 'nlmixr2'.  The models include
 Authors@R: c(
   person("Richard","Hooijmaijers", email="richardhooijmaijers@gmail.com",role="aut"),
   person("Matthew","Fidler", email="richardhooijmaijers@gmail.com",role=c("aut"), comment=c(ORCID="0000-0001-8538-6691")),
-  person("Bill", "Denney", email="wdenney@humanpredictions.com", role=c("aut", "cre"), comment=c(ORCID="0000-0002-5759-428X"))
+  person("Bill", "Denney", email="wdenney@humanpredictions.com", role=c("aut", "cre"), comment=c(ORCID="0000-0002-5759-428X")),
+  person("Kiranmayi", "Vedantham", email="kiranmayi.vedantham@gmail.com", role=c("aut"),comment=c(ORCID="0009-0003-0828-6445"))
   )
 Depends:
     R (>= 4.0)

inst/modeldb/therapeuticArea/oncology/tgi_no_sat_expo.R

@@ -1,11 +1,12 @@
 tgi_no_sat_expo <- function() {
-  description <- "One compartment TGI model with with exponential tumor growth, without saturation."
+  description <- "One-compartment TGI model with exponential tumor growth, without saturation."
   ini({
     lts0 <- 0.8; label("Initial tumor size (TS0)") 
     lka <- 0.45 ; label("Absorption rate (Ka)")
     lcl <- 1 ; label("Clearance (CL)")
     lvc  <- 3.45 ; label("Central volume of distribution (V)")
-    lkge <- 0.7; label("FIrst-order exponential growth rate")
+    lkge <- 0.7; label("First-order exponential growth rate (kge)")
+    lkgl <- 0.7; label("Zero-order linear growth rate (kgl)")
     CcpropSd <- 0.5 ; label("PK proportional residual error (fraction)")
     tumorSizepropSd <- 0.5 ; label("Tumor size proportional residual error (fraction)")
     tumorSizeaddSd <- 30 ; label("Tumor size additive residual error (tumor volume)")
@@ -14,15 +15,17 @@ tgi_no_sat_expo <- function() {
     ts0 <- exp(lts0)
     ka <- exp(lka)
     cl <- exp(lcl)
-    vc  <- exp(lvc)
+    vc <- exp(lvc)
     kge <- exp(lkge)
+    kgl <- exp(lkgl)
 
     kel <- cl / vc
     tumorSize(0) <- ts0
+    tau <- (1 / kge) * log(kgl / (kge * ts0))
 
-    d/dt(depot) <- -ka*depot
-    d/dt(central) <- ka*depot-kel*central
-    d/dt(tumorSize) <- kge*tumorSize
+    d/dt(depot) <- -ka * depot
+    d/dt(central) <- ka * depot - kel * central
+    d/dt(tumorSize) <- ifelse(t <= tau, kge * tumorSize, kgl)
 
     Cc <- central / vc
     Cc ~ prop(CcpropSd)

inst/modeldb/therapeuticArea/oncology/tgi_sat_Gompertz.R

@@ -0,0 +1,37 @@
+tgi_sat_Gompertz<- function() {
+  description <- "One compartment TGI model with tumor growth proportional to tumor size through a generalized logistic function, with saturation."
+  ini({
+    lts0 <- 0.3; label("Initial tumor size (TS0)") 
+    ltsmax <- 0.9; label("Maximum tumor size at saturation (TSmax)")
+    lka <- 0.45 ; label("Absorption rate (Ka)")
+    lcl <- 1 ; label("Clearance (CL)")
+    lvc  <- 3.45 ; label("Central volume of distribution (V)")
+    lkgl <- 0.7; label("Zero-order linear growth rate")
+    lalpha <- 0.6; label("parameter one")
+    lbeta <- 0.8; label("parameter two")
+    CcpropSd <- 0.5 ; label("PK proportional residual error (fraction)")
+    tumorSizepropSd <- 0.5 ; label("Tumor size proportional residual error (fraction)")
+    tumorSizeaddSd <- 30 ; label("Tumor size additive residual error (tumor volume)")
+  })
+  model({
+    ts0 <- exp(lts0)
+    tsmax <- exp(ltsmax)
+    ka <- exp(lka)
+    cl <- exp(lcl)
+    vc  <- exp(lvc)
+    kgl <- exp(lkgl)
+    alpha <- exp(lalpha)
+    beta <- exp(lbeta)
+
+    kel <- cl / vc
+    tumorSize(0) <- ts0
+
+    d/dt(depot) <- -ka*depot
+    d/dt(central) <- ka*depot-kel*central
+    d/dt(tumorSize) <- (alpha-beta*log(tumorSize))*tumorSize
+
+    Cc <- central / vc
+    Cc ~ prop(CcpropSd)
+    tumorSize ~ prop(tumorSizepropSd) + add(tumorSizeaddSd)
+  })
+}

inst/modeldb/therapeuticArea/oncology/tgi_sat_genLogistic.R

@@ -0,0 +1,36 @@
+tgi_sat_genLogistic <- function() {
+  description <- "One compartment TGI model with tumor growth proportional to tumor size through a generalized logistic function, with saturation."
+  ini({
+    lts0 <- 0.3; label("Initial tumor size (TS0)") 
+    ltsmax <- 0.9; label("Maximum tumor size at saturation (TSmax)")
+    lka <- 0.45 ; label("Absorption rate (Ka)")
+    lcl <- 1 ; label("Clearance (CL)")
+    lvc  <- 3.45 ; label("Central volume of distribution (V)")
+    lkgl <- 0.7; label("Zero-order linear growth rate")
+    lgamma <- 0.95; label("proliferative cells as a fraction of the full tumor volume (gamma)")
+    CcpropSd <- 0.5 ; label("PK proportional residual error (fraction)")
+    tumorSizepropSd <- 0.5 ; label("Tumor size proportional residual error (fraction)")
+    tumorSizeaddSd <- 30 ; label("Tumor size additive residual error (tumor volume)")
+  })
+  model({
+    ts0 <- exp(lts0)
+    tsmax <- exp(ltsmax)
+    ka <- exp(lka)
+    cl <- exp(lcl)
+    vc  <- exp(lvc)
+    kgl <- exp(lkgl)
+    gamma <- exp(lgamma)
+
+    kel <- cl / vc
+    tumorSize(0) <- ts0
+
+    d/dt(depot) <- -ka*depot
+    d/dt(central) <- ka*depot-kel*central
+    d/dt(tumorSize) <- kge*tumorSize*(1-(tumorSize/tsmax)^gamma)
+
+    Cc <- central / vc
+    Cc ~ prop(CcpropSd)
+    tumorSize ~ prop(tumorSizepropSd) + add(tumorSizeaddSd)
+
+  })
+}