From 5cbdf4460faa31f83e344bfe2620297df721d892 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Wed, 3 Apr 2024 10:47:33 +0000 Subject: [PATCH 01/15] Test commit from branch Francoistest1 --- R/brier_score.R | 1 + 1 file changed, 1 insertion(+) diff --git a/R/brier_score.R b/R/brier_score.R index 3e1e13b22..77dd512f1 100644 --- a/R/brier_score.R +++ b/R/brier_score.R @@ -1,4 +1,5 @@ +#' Test #' Re-used documentation for Brier Score components #' From b21f519f687b4ea439cbdc9f4cbd0b68059ba8dc Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Wed, 3 Apr 2024 15:19:07 +0000 Subject: [PATCH 02/15] Patrice - Everyday good --- vignettes/.gitignore | 2 +- vignettes/expon-ph-benchmark.R | 126 +++++++++++++++++++++++++++++++ vignettes/expon-ph-benchmark.Rmd | 98 ++++++++++++++++++++++++ 3 files changed, 225 insertions(+), 1 deletion(-) create mode 100644 vignettes/expon-ph-benchmark.R create mode 100644 vignettes/expon-ph-benchmark.Rmd diff --git a/vignettes/.gitignore b/vignettes/.gitignore index 097b24163..3432c3fd8 100644 --- a/vignettes/.gitignore +++ b/vignettes/.gitignore @@ -1,2 +1,2 @@ *.html -*.R + diff --git a/vignettes/expon-ph-benchmark.R b/vignettes/expon-ph-benchmark.R new file mode 100644 index 000000000..17eb6cbbc --- /dev/null +++ b/vignettes/expon-ph-benchmark.R @@ -0,0 +1,126 @@ +#' ############################################################################# +#' +#' Fit exponential model to ‘pb’ data from the {flexsurv} package, +#' using various tools/packages: +#' I. flexsurv +#' II. survstan +#' III. jmpost +#' +#' Initiated on: 2024-03-28 +#' Author: F. Mercier +#' +#' ############################################################################# + + + +#' =========================================================== +#' +#' INSTALL AND LOAD NECESSARY LIBRARIES +#' +#' =========================================================== + +#' General +#' ========================== +library(Rcpp) +library(cli) +library(here) +library(tidyverse) + +#' Survival +#' ========================== +#' install.packages("devtools") +#' install.packages("cmdstanr", repos = c("https://mc-stan.org/r-packages/", getOption("repos"))) +#' devtools::install("~/jmpost") +library(cmdstanr) +library(flexsurv) +library(survstan) +library(jmpost) + + +#' =========================================================== +#' +#' DATA PREP +#' +#' =========================================================== + +#' From the flexsurv package +head(bc, 2) + +#' recyrs represents the time (in years) of death or cancer recurrence when +#' censrec is 1, or (right-)censoring when censrec is 0. +#' The covariate group is a factor representing a prognostic score, with 3 levels: +#' "Good" (the reference), "Medium" and "Poor". +#' In flexsur, the baseline Weibull model is implemented as: +#' S(t) = exp(-(t/mu)^alpha), with alpha=shape param, mu=scale param. +#' group is a linear effect on log(mu) + + +#' =========================================================== +#' +#' Exponential model fits +#' +#' =========================================================== + +#' Flexsurv +#' ========================== +flexsurv.exp<-flexsurvreg(Surv(recyrs, censrec)~group, data=bc, dist="exp") +# flexsurv.exp +# plot(flexsurv.exp) +# flexsurv.exp$AIC +# flexsurv.exp$res + + +#' Survstan +#' ========================== +survstan.exp<-survstan::phreg(Surv(recyrs, censrec)~group, data=bc, dist="exponential") +sumsurvstan<-summary(survstan.exp) +# sumsurvstan$AIC +# sumsurvstan$coefficients +# sumsurvstan$tbl + + +#' jmpost +#' ========================== +jmpost.survonly.exp<-JointModel(survival=SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) + +bc1<-bc %>% mutate(ID=as.character(1:n()), study=1) + +jdat<-DataJoint( + subject=DataSubject(data=bc1, subject="ID", arm="group", study="study"), + survival=DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) + ) + +mp<-sampleStanModel(jmpost.survonly.exp, data=jdat, iter_warmup=4000, + iter_sampling=1000, chains=4, refresh=0) + +vars<-c("sm_exp_lambda", "beta_os_cov") +# mp@results$summary(vars) + + + +#' =========================================================== +#' +#' Pooling results together +#' +#' =========================================================== + +flexsurv.prep<-as_tibble(signif(flexsurv.exp$res, 3)) |> + rename(Estimate=est, SE=se, P025=`L95%`, P975=`U95%`) |> + relocate(SE, .after=Estimate) |> + mutate(meth="flexsurv", rowN=1:3, libel=c("lambda", "beta_group_Medium", "beta_group_Poor"), .before=1) + +survstan.prep1<-as_tibble(signif(sumsurvstan$tbl, 3)) |> + rename(Estimate=estimate, P025=`2.5%`, P975=`97.5%`, SE=se) +survstan.prep2<-as_tibble(signif(sumsurvstan$coefficients[,1:2], 3)) |> + rename(SE=StdErr) |> + mutate(P025=999, P975=999, .after=1) +survstan.prep<-rbind(survstan.prep1, survstan.prep2) |> + mutate(meth="survstan", rowN=1:3, libel=c("lambda", "beta_group_Medium", "beta_group_Poor"), .before=1) + +jmpost.prep<-as_tibble(mp@results$summary(vars)) |> + rename(Estimate=mean, SE=sd, P025=q5, P975=q95) |> + select(Estimate, SE, P025, P975) |> + mutate(meth="jmpost", rowN=1:3, libel=c("lambda", "beta_group_Medium", "beta_group_Poor"), .before=1) + + +altogether<-rbind(flexsurv.prep, survstan.prep, jmpost.prep) diff --git a/vignettes/expon-ph-benchmark.Rmd b/vignettes/expon-ph-benchmark.Rmd new file mode 100644 index 000000000..93c99404c --- /dev/null +++ b/vignettes/expon-ph-benchmark.Rmd @@ -0,0 +1,98 @@ +--- +title: "{jmpost} documentation" +subtitle: "01 // Survival model only // Exponential (PH) model fit" +package: jmpost +output: rmarkdown::html_vignette +vignette: > + %\VignetteIndexEntry{Model Fitting} + %\VignetteEncoding{UTF-8} + %\VignetteEngine{knitr::rmarkdown} +--- + +```{r, include=FALSE} +knitr::opts_chunk$set(echo = TRUE, collapse = TRUE) +``` + + +## Scope of this document +This document describes how to fit survival models implemented in the `jmpost` R package and how the results of this modeling step compare with the ones obtained using other common packages: `flexsurv` and `survstan`. + + +## Survival distributions in a nutshell +The quantity of interest in survival analysis is the probability of survival beyond time $t$, + +$$ +S(t) = Pr(T > t) = 1 - F(t), +$$ +where $T$ is a random variable denoting the time when the event occurs. The survival function is the complement of the cumulative density function (CDF), $F(t) = \int_0^t f(u)du$, where $f(t)$ is the probability density function (PDF). +The hazard function, *i.e.* the instantaneous rate at which an event occurs at time $t$ given survival until time $t$ is given by: + +$$ +\lambda (t) = \frac{f(t)}{S(t)}. +$$ +The survivor function can also be expressed in terms of the cumulative hazard function, $\Lambda(t) = \int_0^t \lambda (u)du$, as follow: +$$ +S(t) = e^{-\Lambda(t)}. +$$ +The default `stats` package contains functions for the PDF, the CDF, and random number generation for many of the distributions. +Additional distributions, as well as support for hazard functions, are provided in `flexsurv`. + + +## Comparing {flexsurv}, {survstan} and {jmpost} + +In this document, the 'bc' dataset from the R package [{flexsurv}](https://chjackson.github.io/flexsurv/) is used. It contains data for 686 patients with primary node positive breast cancer. The variable `recyrs` represents the time (in years) of death or cancer recurrence when `censrec` is 1, or right censoring when `censrec` is 0. The covariate `group` is a factor representing a prognostic score, with 3 levels: "Good" (the reference), "Medium" and "Poor". + +The details of the exponential model implementation in {flexsurv} are provided in the reference article ([DOI](https://www.jstatsoft.org/article/view/v070i08)). +The exponential distribution has a single parameter and only supports a hazard that is constant over time. The hazard is equal to the rate parameter. + +```{r setup, message=FALSE, warning=FALSE} +library(tidyverse) +library(kableExtra) +``` + +```{r, eval=FALSE, echo=TRUE} +flexsurv.exp<-flexsurv::flexsurvreg(Surv(recyrs, censrec)~group, data=bc, dist="exp") +flexsurv.exp +``` + +The same model in {survstan} would be implemented as follow: + +```{r, eval=FALSE, echo=TRUE} +survstan.exp<-survstan::phreg(Surv(recyrs, censrec)~group, data=bc, dist="exponential") +summary(survstan.exp) + +``` + +The same model in {jmpost} would be implemented as follow: + +```{r, eval=FALSE, echo=TRUE} +jm<-JointModel(survival= + SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) + +bc1<-bc %>% + mutate(ID=as.character(1:n()), study=1) +jdat<-DataJoint( + subject = DataSubject(data=bc1, subject="ID", arm="group", study="study"), + survival = DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) +) + +mp<-sampleStanModel(jm, data=jdat, iter_warmup=4000, iter_sampling=1000, chains=4) +vars<-c("sm_exp_lambda", "beta_os_cov") +mp@results$summary(vars) + +``` + +As shown in the below table, these various model calls provide consistent outputs. +More details on the {jmpost} outputs are provided in the separate vignette ABC123. + +```{r, file="expon-ph-benchmark.R", echo=FALSE} +library(knitr) +library(kableExtra) + +# Create table +altogether %>% + kable(escape = F) %>% + kable_styling() +``` + + From 36ee5b94bd0a02e87c3c50ae25a726a2e0d1e969 Mon Sep 17 00:00:00 2001 From: github-actions <41898282+github-actions[bot]@users.noreply.github.com> Date: Wed, 3 Apr 2024 15:25:17 +0000 Subject: [PATCH 03/15] [skip roxygen] [skip vbump] Roxygen Man Pages Auto Update --- man/Brier-Score-Shared.Rd | 4 +++- 1 file changed, 3 insertions(+), 1 deletion(-) diff --git a/man/Brier-Score-Shared.Rd b/man/Brier-Score-Shared.Rd index a9c7e6869..ea9eb9539 100644 --- a/man/Brier-Score-Shared.Rd +++ b/man/Brier-Score-Shared.Rd @@ -2,7 +2,8 @@ % Please edit documentation in R/brier_score.R \name{Brier-Score-Shared} \alias{Brier-Score-Shared} -\title{Re-used documentation for Brier Score components} +\title{Test +Re-used documentation for Brier Score components} \arguments{ \item{t}{(\code{numeric})\cr timepoints to calculate the desired quantity at.} @@ -22,6 +23,7 @@ package.} \item{...}{not used.} } \description{ +Test Re-used documentation for Brier Score components } \keyword{internal} From b2ba18ddd5f54c0fd360524ac30fc9dfc7794beb Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Tue, 9 Apr 2024 15:50:19 +0000 Subject: [PATCH 04/15] Anna Majidson - Natasha --- vignettes/expon-ph-benchmark.Rmd | 98 --------- vignettes/expon-ph-outputs.R | 243 +++++++++++++++++++++ vignettes/survival_standalone.Rmd | 339 ++++++++++++++++++++++++++++++ 3 files changed, 582 insertions(+), 98 deletions(-) delete mode 100644 vignettes/expon-ph-benchmark.Rmd create mode 100644 vignettes/expon-ph-outputs.R create mode 100644 vignettes/survival_standalone.Rmd diff --git a/vignettes/expon-ph-benchmark.Rmd b/vignettes/expon-ph-benchmark.Rmd deleted file mode 100644 index 93c99404c..000000000 --- a/vignettes/expon-ph-benchmark.Rmd +++ /dev/null @@ -1,98 +0,0 @@ ---- -title: "{jmpost} documentation" -subtitle: "01 // Survival model only // Exponential (PH) model fit" -package: jmpost -output: rmarkdown::html_vignette -vignette: > - %\VignetteIndexEntry{Model Fitting} - %\VignetteEncoding{UTF-8} - %\VignetteEngine{knitr::rmarkdown} ---- - -```{r, include=FALSE} -knitr::opts_chunk$set(echo = TRUE, collapse = TRUE) -``` - - -## Scope of this document -This document describes how to fit survival models implemented in the `jmpost` R package and how the results of this modeling step compare with the ones obtained using other common packages: `flexsurv` and `survstan`. - - -## Survival distributions in a nutshell -The quantity of interest in survival analysis is the probability of survival beyond time $t$, - -$$ -S(t) = Pr(T > t) = 1 - F(t), -$$ -where $T$ is a random variable denoting the time when the event occurs. The survival function is the complement of the cumulative density function (CDF), $F(t) = \int_0^t f(u)du$, where $f(t)$ is the probability density function (PDF). -The hazard function, *i.e.* the instantaneous rate at which an event occurs at time $t$ given survival until time $t$ is given by: - -$$ -\lambda (t) = \frac{f(t)}{S(t)}. -$$ -The survivor function can also be expressed in terms of the cumulative hazard function, $\Lambda(t) = \int_0^t \lambda (u)du$, as follow: -$$ -S(t) = e^{-\Lambda(t)}. -$$ -The default `stats` package contains functions for the PDF, the CDF, and random number generation for many of the distributions. -Additional distributions, as well as support for hazard functions, are provided in `flexsurv`. - - -## Comparing {flexsurv}, {survstan} and {jmpost} - -In this document, the 'bc' dataset from the R package [{flexsurv}](https://chjackson.github.io/flexsurv/) is used. It contains data for 686 patients with primary node positive breast cancer. The variable `recyrs` represents the time (in years) of death or cancer recurrence when `censrec` is 1, or right censoring when `censrec` is 0. The covariate `group` is a factor representing a prognostic score, with 3 levels: "Good" (the reference), "Medium" and "Poor". - -The details of the exponential model implementation in {flexsurv} are provided in the reference article ([DOI](https://www.jstatsoft.org/article/view/v070i08)). -The exponential distribution has a single parameter and only supports a hazard that is constant over time. The hazard is equal to the rate parameter. - -```{r setup, message=FALSE, warning=FALSE} -library(tidyverse) -library(kableExtra) -``` - -```{r, eval=FALSE, echo=TRUE} -flexsurv.exp<-flexsurv::flexsurvreg(Surv(recyrs, censrec)~group, data=bc, dist="exp") -flexsurv.exp -``` - -The same model in {survstan} would be implemented as follow: - -```{r, eval=FALSE, echo=TRUE} -survstan.exp<-survstan::phreg(Surv(recyrs, censrec)~group, data=bc, dist="exponential") -summary(survstan.exp) - -``` - -The same model in {jmpost} would be implemented as follow: - -```{r, eval=FALSE, echo=TRUE} -jm<-JointModel(survival= - SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) - -bc1<-bc %>% - mutate(ID=as.character(1:n()), study=1) -jdat<-DataJoint( - subject = DataSubject(data=bc1, subject="ID", arm="group", study="study"), - survival = DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) -) - -mp<-sampleStanModel(jm, data=jdat, iter_warmup=4000, iter_sampling=1000, chains=4) -vars<-c("sm_exp_lambda", "beta_os_cov") -mp@results$summary(vars) - -``` - -As shown in the below table, these various model calls provide consistent outputs. -More details on the {jmpost} outputs are provided in the separate vignette ABC123. - -```{r, file="expon-ph-benchmark.R", echo=FALSE} -library(knitr) -library(kableExtra) - -# Create table -altogether %>% - kable(escape = F) %>% - kable_styling() -``` - - diff --git a/vignettes/expon-ph-outputs.R b/vignettes/expon-ph-outputs.R new file mode 100644 index 000000000..75e744ee0 --- /dev/null +++ b/vignettes/expon-ph-outputs.R @@ -0,0 +1,243 @@ +#' ############################################################################# +#' +#' For a time to event model of ‘pb’ data from the {flexsurv} package, +#' assuming an exponential baseline hazard, the goal here is to +#' illustrate the way to assess: +#' (i) Convergence +#' (ii) GoF +#' +#' Solutions proposed by {survstan} will be used as benchmark +#' +#' Initiated on: 2024-02-14 +#' Author: F. Mercier +#' +#' ############################################################################# + + + +#' =========================================================== +#' +#' INSTALL AND LOAD NECESSARY LIBRARIES +#' +#' =========================================================== + +#' install.packages(c("Rcpp", "cli")) +library(Rcpp) +library(cli) +library(here) +#' install.packages("tidyverse") +library(tidyverse) + +library(flexsurv) +library(cmdstanr) + +#' install.packages("tidybayes") +library(posterior) +library(bayesplot) +library(tidybayes) +#' install.packages("bayestestR") +library(distributional) +library(ggdist) +library(bayestestR) +#' install.packages("hexbin") +library(hexbin) +library(loo) + + +#' =========================================================== +#' +#' Data (from the flexsurv package) +#' +#' =========================================================== + +head(bc, 2) +glimpse(bc) + + +#' =========================================================== +#' +#' jmpost exponential PH implementation +#' +#' =========================================================== + +jmpost.survonly.exp<-JointModel(survival=SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) + +bc1<-bc %>% mutate(ID=as.character(1:n()), study=1) + +jdat<-DataJoint( + subject=DataSubject(data=bc1, subject="ID", arm="group", study="study"), + survival=DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) +) + +mp<-sampleStanModel(jmpost.survonly.exp, data=jdat, iter_warmup=4000, + iter_sampling=1000, chains=4, refresh=0) + +vars<-c("sm_exp_lambda", "beta_os_cov") +# mp@results$summary(vars) + + +#' =========================================================== +#' +#' I. POSTERIOR DISTRIBUTION SUMMARY +#' +#' =========================================================== + + +#' Convert the samples in a df +#' ------------------------------------------------------------\ +my_fit_df <- posterior::as_draws_df(mp@results) +my_pars<-c("sm_exp_lambda", "beta_os_cov[1]", "beta_os_cov[2]") + + +#' Summarize the posterior samples +#' ------------------------------------------------------------\ +#' Using {posterior} +posterior::summarise_draws(my_fit_df) + + +#' Highest density interval +#' ------------------------------------------------------------\ +#' Using {posterior} +ci_hdi <- bayestestR::ci(my_fit_df, method = "HDI") + +#' Using {tidybayes} +my_fit_df %>% + tidybayes::recover_types() + +#' For each parameter, it is possible to extract various quantities: +#' mean_hdci(), median_hdci(), etc ... from [median|mean|mode]_[qi|hdi] +#' see: ggdist:: ?mean_qi +my_fit_df %>% + tidybayes::spread_rvars(sm_weibull_ph_lambda) %>% + tidybayes::mean_hdci() +my_fit_df %>% + tidybayes::spread_rvars(sm_weibull_ph_lambda) %>% + tidybayes::mean_qi() + +#' Median (and associated uncertainty expressed as lower and upper bounds for +#' pmf containing 50%, 89%, 90% of the distribution density +#' = e.g. 89% credibility interval for the median) +#' for sm_weibull_ph_lambda across all chains +my_fit_df %>% + tidybayes::spread_rvars(sm_weibull_ph_lambda) %>% + tidybayes::median_qi(.width = c(.50, .89, .95)) + +#' Q1, median, Q3 of sm_weibull_ph_lambda across all chains +lambda_samples<-my_fit_df %>% + tidybayes::spread_draws(sm_weibull_ph_lambda) +lambda_samples$sm_weibull_ph_lambda %>% quantile(., probs=c(0.25, 0.5, 0.75)) + + +#' Posterior density +#' using tidybayes see https://mjskay.github.io/tidybayes/articles/tidy-rstanarm.html +#' ------------------------------------------------------------\ + +my_fit_df %>% + tidybayes::spread_draws(sm_weibull_ph_lambda) %>% + tidybayes::median_qi(., .width = c(.95, .66)) %>% + ggplot(aes(y = NA, x = sm_weibull_ph_lambda, xmin = .lower, xmax = .upper)) + + scale_x_continuous("Lambda_0")+ + scale_y_discrete("")+ + tidybayes::geom_pointinterval()+ + labs(title="sm_weibull_ph_lambda posterior distributions", + caption="OS analysis / mercief3 / 2024-02-20")+ + theme_minimal() + +#' (Post-warmup) Posterior distributions +#' ------------------------------------------------------------\ +bayesplot::mcmc_areas(my_fit_df, pars = my_pars, prob = 0.8)+ + theme_minimal() +bayesplot::mcmc_dens_overlay(my_fit_df, pars=my_pars)+ + theme_minimal() + +#' Scale vs. shape scatterplot +#' ------------------------------------------------------------\ +bayesplot::mcmc_hex(my_fit_df, pars=c("sm_weibull_ph_lambda", "sm_weibull_ph_gamma"))+ + theme_minimal() + + + +#' =========================================================== +#' +#' II. CONVERGENCE +#' +#' =========================================================== + + +#' Checking that Rhat<1.05 +#' ------------------------------------------------------------\ +#' Using {posterior} +#' see https://cran.r-project.org/web/packages/bayesplot/vignettes/visual-mcmc-diagnostics.html +posterior::summarise_draws(my_fit_df) + +#' Using {bayesplot} +rhats <- bayesplot::rhat(mp@results) +print(rhats) +color_scheme_set("brightblue") # see help("color_scheme_set") +bayesplot::mcmc_rhat(rhats)+ yaxis_text(hjust = 1) + + +#' Checking ESS +#' ------------------------------------------------------------\ +#' Using {bayesplot} +#' see https://cran.r-project.org/web/packages/bayesplot/vignettes/visual-mcmc-diagnostics.html +neff_ratios <- bayesplot::neff_ratio(mp@results) +print(neff_ratios) +color_scheme_set("brightblue") # see help("color_scheme_set") +bayesplot::mcmc_neff(neff_ratios, size = 2)+ yaxis_text(hjust = 1) + + +#' Checking autocorrelation +#' ------------------------------------------------------------\ +#' Using {bayesplot} +#' see https://cran.r-project.org/web/packages/bayesplot/vignettes/visual-mcmc-diagnostics.html +bayesplot::mcmc_acf_bar(my_fit_df, pars="sm_weibull_ph_lambda", lags=10)+ + theme_minimal() + + +#' Caterpillar plot for each param +#' ------------------------------------------------------------\ +bayesplot::mcmc_trace(my_fit_df, pars = my_pars)+ + theme_minimal() + + + +#' =========================================================== +#' +#' III. GOODNESS OF FIT +#' +#' =========================================================== + +# Log Likelihood +#' =========================================================== +log_lik <- mp@results$draws("log_lik", format = "draws_matrix") |> + apply(1, sum) |> + mean() +log_lik + +# AIC +k <- 2 +-2 * log_lik + k * 4 + +# BIC +(4 * log(nrow(bc1))) + (-2 * log_lik) + +# Leave one out CV +mp@results$loo() + + + + + +#' =========================================================== +#' +#' IV. PREDICTIONS +#' +#' Overlaying KM and posterior survival curves +#' See example: +#' https://stablemarkets.netlify.app/post/post2/specifying-accelerated-failure-time-models-in-stan/ +#' +#' +#' =========================================================== + + diff --git a/vignettes/survival_standalone.Rmd b/vignettes/survival_standalone.Rmd new file mode 100644 index 000000000..cd9ef1d77 --- /dev/null +++ b/vignettes/survival_standalone.Rmd @@ -0,0 +1,339 @@ +--- +title: "{jmpost} documentation" +subtitle: "01. Survival models" +package: jmpost +output: rmarkdown::html_vignette +vignette: > + %\VignetteIndexEntry{Model Fitting} + %\VignetteEncoding{UTF-8} + %\VignetteEngine{knitr::rmarkdown} +editor_options: + chunk_output_type: console + markdown: + wrap: 72 +--- + +```{r, include=FALSE} +knitr::opts_chunk$set(echo = TRUE, collapse = TRUE) +``` + +## Scope of this document + +This document describes how to analyze survival data using parametric +survival models implemented in the **jmpost** R package. It is organized +in 4 sections: + +1. Introduction + +2. Survival model framework + +3. Fitting a simple survival model in **jmpost** + +4. Comparing with **flexsurv** and **survstan** outputs + +## 1. Introduction + +Survival (or time-to-event, or failure time) analysis is concerned with +the study of survival times and factors influencing them. + +There are 3 common approaches to modelling survival data: + +1. Models of the instantaneous rate of the event (known as the hazard) + as a function of time taken as a continuous variable. This includes + the well-known class of proportional hazards (PH) regression models. + +2. Models the event time itself, again considering time as a continuous + variable, including the accelerated failure time (AFT) models. + +3. Models of the occurrence of event when time is taken as a discrete + variable, specifically the additive hazard regression (AHR) model. + +In the current version of **jmpost**, we focus on approach 1., and +specifically on PH models, implemented in a Bayesian framework. + +Proportional hazard (PH) models play an important role in analyzing +survival and rely on a key assumption: the hazard ratio (HR) comparing +any two levels of a covariate is constant over time. The Cox PH model is +most popular for two reasons: (a) no assumption is required about the +probability distribution of survival times, and (b) it fits the data +reasonably well no matter which parametric model is appropriate. + +In contrast, distributional assumption is required for a fully +parametric PH model (Kalbfleisch and Prentice 2002 :: The Statistical +Analysis of Failure Time Data. John Wiley & Sons, New Jersey; Lawless +2002 :: Statistical Models and Methods for Lifetime Data. John Wiley & +Sons, New Jersey (2002)). When the distribution is selected wisely, +parametric models lead to more efficient (i.e. smaller standard errors) +estimates than Cox's model (Collett 2003 :: Modelling Survival Data in +Medical Research. Chapman and Hall/CRC, Florida). + +Moreover, the use of Cox PH in joint modeling of time-to-event and +longitudinal data (Wulfsohn and Tsiatis 1997 :: A joint model for +survival and longitudinal data measured with errror. Biometrics. 53, +330--339) usually leads to an underestimation of the parameter estimates +standard errors (Hsieh et al. 2006 :: Joint modeling of survival and +longitudinal data: Likelihood approach revisited. Biometrics. 62, +1037--1043; Rizopoulos 2012 :: Joint Models for Longitudinal and +Time-to-Event Data With Applications in R. Chapman and Hall/CRC, +Florida). Therefore, most methods for joint modeling are based on +parametric response distributions (Hwang and Pennell 2014 :: +Semiparametric bayesian joint modeling of a binary and continuous +outcome with applications in toxicological risk assessment. Stat. Med. +33, 1162--1175). + +Bayesian inference offers the opportunity + +- to make probability statements about parameters, + +- to handle hierarchical structures naturally, + +- to have good statistical properties when dealing with small samples, and + +- to quantify uncertainty in predicted quantities easily. + +All these properties are convenient for joint models, but also +for survival models taken separately. + +**jmpost** is written in Stan, a high-level language (itself written in +a C++) for Bayesian modeling and inference that primarily uses a version +of the No-U-Turn sampler (NUTS) (Hoffman & Gelman, 2014 :: Hoffman, M. +D., & Gelman, A. (2014). The No-U-turn sampler: Adaptively setting path +lengths in Hamiltonian Monte Carlo. Journal of Machine Learning +Research, 15(47), 1593-1623) to obtain posterior samples given a +user-specified model and data. + +Although Stan is an extremely flexible and powerful software for +statistical modelling, it is neither user-friendly nor easy to learn. To +remove this hurdle, we propose **jmpost** as a layer on top of Stan to +facilitate the encoding of PH models, either stand-alone, or integrated +in joint models. + +## 2. Survival model framework + +Let $T^*_i$ denote a continuous non-negative random variable +representing survival time for individual $i$ (with $i=1, ..., n$). + +In reality, the event time $T^*_i$ may not be observed due to +right-censoring; for instance, the event may occur after the end of the +clinical study, denoted $\tau_f$. We define the outcome as the pair: +$T_i$ being the observed event or censoring time (with $T_i>0$) and +$d_i \in \{0,1\}$, an indicator taking value 0 in case of right +censoring (i.e. $T^*_i>\tau_f$), or value 1 if the event is observed +(i.e. $T^*_i=T_i$). + +Three key quantities form the likelihood function for survival models: +the hazard rate, the cumulative hazard, and the survival probability. + +The survival function $S(t, \psi_i)$ gives the probability that the +event happens to individual $i$ after time t, where $\psi_i$ represent +the individual parameters. +$$ +S(t, \psi_i) = P(T_i>t; \psi_i) +$$ + +The hazard function $h(t, \psi_i)$ is the instantaneous rate of occurrence of the event for individual $i$ at time $t$, given that the event has not already occurred. Mathematically, it is defined as: +$$ +h(t, \psi_i) = \displaystyle \lim_{dt \to 0} \displaystyle \frac{P(t \le T_i < t+dt \mid T_i > t)}{dt} +$$ +where $dt$ is a small time interval. + +This is equivalent to: +$$ +h(t, \psi_i)= - \frac{d}{dt} \log S(t, \psi_i) +$$ +Knowing the hazard function gives access to the survival function. + +The cumulative hazard is defined as: +$$ +H(a, b, \psi_i)=\int_{a}^{b} h(t, \psi_i) \; dt +$$ + +which implies that: +$$ +S(t, \psi_i) = \exp(-H(0, t, \psi_i)) +$$ + +The log-likelihood function in presence of right-censoring measures the risk of experiencing the event at any time point $t$, conditionally on that individual $i$ has in fact survival until that time point; if s/he has not survived, then the probability of experiencing the event again is 0: +$$ +log \mathcal{L}=\sum_{i = 1}^{n} \left[ d_i \log h(t, \psi_i) + \log S(t, \psi_i) \right] +$$ + +When formulating a parametric survival model, we need to specify the form of the probability distribution assumed to describe the underlying uncertainty in the observed times. + +In general terms, we can specify the vector of relevant parameters as $\theta = (μ(x), \alpha(x))$. In this notation, consistent with **flexsurv**, we consider: + +- a vector of potential covariates $x$ (e.g., treatment group, age, or sex), + +- a *location* parameter $\mu(x)$, which indicates the *mean* or the *scale* of the probability distribution, + +- and a (set of) ancillary parameters $\alpha(x)$, which describe the *shape* or *variance* of the distribution. + +While it is possible for both $\mu$ and $\alpha$ to explicitly depend on the covariates $x$, usually the formulation is simplified to assume that these only affect directly the location parameter. + +To parameterize the effect of covariates on the location parameter, a generalized linear formulation is employed: +$$ +g(\mu_i)=\beta_0+\sum_{k = 1}^{K} \beta_k x_ik +$$ +The function $g(.)$ is typically the logarithm, but alternative transformations such as square-root or Box-Cox could also be considered. + +We model the hazard of event for individual $i$ at time $t$ using the regression model: +$$ +h(t, \psi_i)=h_0(t) \exp(\beta_0+\sum_{k = 1}^{K} \beta_k x_{ik}) +$$ +where $h_0(t)$ is the baseline hazard (i.e. the hazard for an individual with the covariates set equals to zero) at time $t$, and the terms in $exp(.)$ denotes the linear predictors evaluated for individual $i$ at time $t$. + +The following distributional assumptions for the baseline hazard are currently implemented in the **jmpost** package: + +1- Exponential + +2- Weibull + +3- Log-logistic + +The following table shows the location and ancillary parameter with their default priors. + +```{r setup, message=FALSE, warning=FALSE} +library(knitr) +library(kableExtra) +library(flexsurv) +``` + +```{r distributiontable, echo=FALSE} +ztab <- data.frame( + Dist = c("\\( \\ T_i \\sim \\exp(\\mu_i) \\)", + "\\( \\ T_i \\sim Weibull(\\mu_i, \\alpha) \\)", + "\\( \\ T_i \\sim logLogistic(\\mu_i, \\alpha) \\)"), + Loca = c("\\( \\ Rate: \\mu_i=\\exp(\\beta_0+\\sum_{k = 1}^{K} \\beta_k x_{ik}) \\)", + "\\( \\ Scale: \\mu_i= (idem) \\)", + "\\( \\ Rate: \\mu_i= (idem) \\)"), + Shap = c("\\( NA \\)", + "\\( \\ Shape: \\alpha \\sim \\gamma(0.1, 0.1) \\)", + "\\( \\ Shape: \\alpha \\sim \\gamma(0.1, 0.1) \\)") +) + +# Create table +knitr::kable(ztab, + escape = F, + caption = 'Table example', + col.names = c("Distribution", "Location (or Scale)", "Shape")) +``` + +The models implemented in **jmpost** all have a PH parameterization. + + +## 3. Fitting a simple survival model in jmpost + +### 3.1. Call + +In the following, we run a simple example to present the features of **jmpost**. + +The 'bc' dataset from [**flexsurv**](https://chjackson.github.io/flexsurv/) is used. It contains data for 686 patients with primary node positive breast cancer. The right-censored time-to-event variable `recyrs` represents the time (in years) of death or cancer recurrence when `censrec` is 1, or right censoring when `censrec` is 0. The covariate `group` is a factor representing a prognostic score, with 3 levels: "Good" (the reference), "Medium" and "Poor". + +Showing the first 6 and the last 6 rows, the dataset looks like this: +```{r, eval=TRUE, echo=TRUE} +rbind(head(bc), tail(bc)) +``` + +The call to fit an exponential PH model in **jmpost** would be as follow: + +```{r, eval=FALSE, echo=TRUE} +jm<-JointModel(survival= + SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) + +bc1<-bc %>% + mutate(ID=as.character(1:n()), study=1) +jdat<-DataJoint( + subject = DataSubject(data=bc1, subject="ID", arm="group", study="study"), + survival = DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) +) + +mp<-sampleStanModel(jm, data=jdat, iter_warmup=4000, iter_sampling=1000, chains=4) +vars<-c("sm_exp_lambda", "beta_os_cov") +mp@results$summary(vars) + +``` + +Details about the parameters and functions are available in the [Model Fitting](https://genentech.github.io/jmpost/main/articles/model_fitting.html). + +### 3.2 Default outputs + +The default output reports statistics for one or more sampler chains over all model parameters and quantities of interest. +The statistics reported include both summary statistics of the estimates and diagnostic statistics on the sampler chains, reported in the following order: +- mean: sample mean, +- median: sample median, +- sd: sample standard deviation, +- q5, q95: 5th and 95th percentiles of the posterior distribution, +- rhat: + + +```{r} + +#' Convert the samples in a df +#' ------------------------------------------------------------\ +mp@results$summary(vars) + +my_fit_df <- posterior::as_draws_df(mp@results) +my_pars<-c("sm_exp_lambda", "beta_os_cov[1]", "beta_os_cov[2]") + + +#' Summarize the posterior samples +#' ------------------------------------------------------------\ +#' Using {posterior} +posterior::summarise_draws(my_fit_df) + +``` + + +### 3.3 Goodness-of-fit evaluation + + +### 3.4 Observed vs. fitted survival + + + + From 1ad457480b1d8d921048c8a6eb4d2063746cea25 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Mon, 3 Jun 2024 15:23:25 +0000 Subject: [PATCH 05/15] Former code from Francois --- vignettes/expon-ph-benchmark.R | 52 ++++++++-- vignettes/expon-ph-outputs.R | 167 +++++++++++++++++++----------- vignettes/survival_standalone.Rmd | 87 ++++++++++++---- 3 files changed, 212 insertions(+), 94 deletions(-) diff --git a/vignettes/expon-ph-benchmark.R b/vignettes/expon-ph-benchmark.R index 17eb6cbbc..b35a92159 100644 --- a/vignettes/expon-ph-benchmark.R +++ b/vignettes/expon-ph-benchmark.R @@ -1,6 +1,6 @@ #' ############################################################################# #' -#' Fit exponential model to ‘pb’ data from the {flexsurv} package, +#' Fit Weibull PH model to ‘pb’ data from the {flexsurv} package, #' using various tools/packages: #' I. flexsurv #' II. survstan @@ -57,43 +57,64 @@ head(bc, 2) #' =========================================================== #' -#' Exponential model fits +#' Weibull PH model fits #' #' =========================================================== #' Flexsurv #' ========================== -flexsurv.exp<-flexsurvreg(Surv(recyrs, censrec)~group, data=bc, dist="exp") +# flexsurv.exp<-flexsurvreg(Surv(recyrs, censrec)~group, data=bc, dist="exp") # flexsurv.exp # plot(flexsurv.exp) # flexsurv.exp$AIC # flexsurv.exp$res +flexsurv.weiph<-flexsurvreg(Surv(recyrs, censrec)~group, data=bc, dist="weibullph") +flexsurv.weiph #' Survstan #' ========================== -survstan.exp<-survstan::phreg(Surv(recyrs, censrec)~group, data=bc, dist="exponential") -sumsurvstan<-summary(survstan.exp) +# survstan.exp<-survstan::phreg(Surv(recyrs, censrec)~group, data=bc, dist="exponential") +# sumsurvstan<-summary(survstan.exp) # sumsurvstan$AIC # sumsurvstan$coefficients # sumsurvstan$tbl +survstan.weiph<-survstan::phreg(Surv(recyrs, censrec)~group, data=bc, dist="weibull") +summary(survstan.weiph) + #' jmpost #' ========================== -jmpost.survonly.exp<-JointModel(survival=SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) +# jmpost.survonly.exp<-JointModel(survival=SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) + +# bc1<-bc %>% mutate(ID=as.character(1:n()), study=1) + +# jdat<-DataJoint( +# subject=DataSubject(data=bc1, subject="ID", arm="group", study="study"), +# survival=DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) +# ) + +# mp<-sampleStanModel(jmpost.survonly.exp, data=jdat, iter_warmup=4000, +# iter_sampling=1000, chains=4, refresh=0) + +# vars<-c("sm_exp_lambda", "beta_os_cov") +# mp@results$summary(vars) + +jmpost.weiph<-JointModel(survival=SurvivalWeibullPH()) bc1<-bc %>% mutate(ID=as.character(1:n()), study=1) jdat<-DataJoint( - subject=DataSubject(data=bc1, subject="ID", arm="group", study="study"), - survival=DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) - ) + subject=DataSubject(data=bc1, subject="ID", arm="group", study="study"), + survival=DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) +) -mp<-sampleStanModel(jmpost.survonly.exp, data=jdat, iter_warmup=4000, +mp<-sampleStanModel(jmpost.weiph, data=jdat, iter_warmup=4000, iter_sampling=1000, chains=4, refresh=0) +mp@results -vars<-c("sm_exp_lambda", "beta_os_cov") +# vars<-c("sm_exp_lambda", "beta_os_cov") # mp@results$summary(vars) @@ -124,3 +145,12 @@ jmpost.prep<-as_tibble(mp@results$summary(vars)) |> altogether<-rbind(flexsurv.prep, survstan.prep, jmpost.prep) + + + + + + + + + diff --git a/vignettes/expon-ph-outputs.R b/vignettes/expon-ph-outputs.R index 75e744ee0..6b70a85f2 100644 --- a/vignettes/expon-ph-outputs.R +++ b/vignettes/expon-ph-outputs.R @@ -1,13 +1,13 @@ #' ############################################################################# #' -#' For a time to event model of ‘pb’ data from the {flexsurv} package, +#' For a time to event model of ‘pb’ data from the {flexsurv} package, #' assuming an exponential baseline hazard, the goal here is to #' illustrate the way to assess: #' (i) Convergence #' (ii) GoF -#' +#' #' Solutions proposed by {survstan} will be used as benchmark -#' +#' #' Initiated on: 2024-02-14 #' Author: F. Mercier #' @@ -16,9 +16,9 @@ #' =========================================================== -#' +#' #' INSTALL AND LOAD NECESSARY LIBRARIES -#' +#' #' =========================================================== #' install.packages(c("Rcpp", "cli")) @@ -43,23 +43,54 @@ library(bayestestR) library(hexbin) library(loo) +library(jmpost) + + +#' install.packages("simsurv") +#' install.packages("ggsurvfit") +library(simsurv) +library(ggsurvfit) #' =========================================================== -#' +#' #' Data (from the flexsurv package) -#' +#' #' =========================================================== head(bc, 2) glimpse(bc) +rbind(head(bc), tail(bc)) + +#' Kaplan-Meier plot and Risk table +p001 <- ggsurvfit::survfit2(Surv(recyrs, censrec) ~ group, data = bc) |> + ggsurvfit(linewidth = 1) + + add_confidence_interval() + + add_risktable() + + add_quantile(y_value = 0.5, color = "gray50", linewidth = 0.75) + + scale_ggsurvfit() +p001 + +#' Checking independent censoring +p002 <- ggsurvfit::survfit2(Surv(recyrs, 1-censrec) ~ group, data = bc) |> + ggsurvfit(linewidth = 1) + + add_confidence_interval() + + scale_ggsurvfit() +p002 + +#' Kernel density estimate for the hazard +futime=bc$recyrs; fustat=bc$censrec +fit1 <- muhaz::muhaz(futime, fustat, bw.method="g") +plot(fit1) +summary(fit1) #' =========================================================== -#' +#' #' jmpost exponential PH implementation -#' +#' #' =========================================================== + jmpost.survonly.exp<-JointModel(survival=SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) bc1<-bc %>% mutate(ID=as.character(1:n()), study=1) @@ -72,103 +103,91 @@ jdat<-DataJoint( mp<-sampleStanModel(jmpost.survonly.exp, data=jdat, iter_warmup=4000, iter_sampling=1000, chains=4, refresh=0) +mp@results + vars<-c("sm_exp_lambda", "beta_os_cov") # mp@results$summary(vars) #' =========================================================== -#' +#' #' I. POSTERIOR DISTRIBUTION SUMMARY -#' +#' #' =========================================================== #' Convert the samples in a df #' ------------------------------------------------------------\ -my_fit_df <- posterior::as_draws_df(mp@results) +my_fitall_df <- posterior::as_draws_df(mp@results) my_pars<-c("sm_exp_lambda", "beta_os_cov[1]", "beta_os_cov[2]") - +my_fitpop_df<-posterior::subset_draws(my_fitall_df, variable=my_pars) #' Summarize the posterior samples #' ------------------------------------------------------------\ #' Using {posterior} -posterior::summarise_draws(my_fit_df) +posterior::summarise_draws(my_fitpop_df) -#' Highest density interval +#' Quantiles or Highest density interval #' ------------------------------------------------------------\ -#' Using {posterior} -ci_hdi <- bayestestR::ci(my_fit_df, method = "HDI") - -#' Using {tidybayes} -my_fit_df %>% - tidybayes::recover_types() - #' For each parameter, it is possible to extract various quantities: #' mean_hdci(), median_hdci(), etc ... from [median|mean|mode]_[qi|hdi] #' see: ggdist:: ?mean_qi -my_fit_df %>% - tidybayes::spread_rvars(sm_weibull_ph_lambda) %>% - tidybayes::mean_hdci() -my_fit_df %>% - tidybayes::spread_rvars(sm_weibull_ph_lambda) %>% - tidybayes::mean_qi() - -#' Median (and associated uncertainty expressed as lower and upper bounds for -#' pmf containing 50%, 89%, 90% of the distribution density +my_fitpop_df %>% + tidybayes::spread_rvars(sm_exp_lambda) %>% + ggdist::mean_hdci() +my_fitpop_df %>% + tidybayes::spread_rvars(sm_exp_lambda) %>% + ggdist::mean_qi() + +#' Median (and associated uncertainty expressed as lower and upper bounds for +#' pmf containing 50%, 89%, 90% of the distribution density #' = e.g. 89% credibility interval for the median) -#' for sm_weibull_ph_lambda across all chains -my_fit_df %>% - tidybayes::spread_rvars(sm_weibull_ph_lambda) %>% +#' for sm_exp_lambda across all chains +my_fitpop_df %>% + tidybayes::spread_rvars(sm_exp_lambda) %>% tidybayes::median_qi(.width = c(.50, .89, .95)) -#' Q1, median, Q3 of sm_weibull_ph_lambda across all chains -lambda_samples<-my_fit_df %>% - tidybayes::spread_draws(sm_weibull_ph_lambda) -lambda_samples$sm_weibull_ph_lambda %>% quantile(., probs=c(0.25, 0.5, 0.75)) +#' Q1, median, Q3 of sm_exp_lambda across all chains +lambda_samples<-my_fitpop_df %>% + tidybayes::spread_draws(sm_exp_lambda) +lambda_samples$sm_exp_lambda %>% quantile(., probs=c(0.025, 0.5, 0.975)) #' Posterior density #' using tidybayes see https://mjskay.github.io/tidybayes/articles/tidy-rstanarm.html #' ------------------------------------------------------------\ -my_fit_df %>% - tidybayes::spread_draws(sm_weibull_ph_lambda) %>% +my_fitpop_df %>% + tidybayes::spread_draws(sm_exp_lambda) %>% tidybayes::median_qi(., .width = c(.95, .66)) %>% - ggplot(aes(y = NA, x = sm_weibull_ph_lambda, xmin = .lower, xmax = .upper)) + + ggplot(aes(y = NA, x = sm_exp_lambda, xmin = .lower, xmax = .upper)) + scale_x_continuous("Lambda_0")+ scale_y_discrete("")+ tidybayes::geom_pointinterval()+ - labs(title="sm_weibull_ph_lambda posterior distributions", + labs(title="sm_exp_lambda posterior distributions", caption="OS analysis / mercief3 / 2024-02-20")+ theme_minimal() #' (Post-warmup) Posterior distributions #' ------------------------------------------------------------\ -bayesplot::mcmc_areas(my_fit_df, pars = my_pars, prob = 0.8)+ +bayesplot::mcmc_areas(my_fitpop_df, pars = my_pars, prob = 0.8)+ theme_minimal() -bayesplot::mcmc_dens_overlay(my_fit_df, pars=my_pars)+ - theme_minimal() - -#' Scale vs. shape scatterplot -#' ------------------------------------------------------------\ -bayesplot::mcmc_hex(my_fit_df, pars=c("sm_weibull_ph_lambda", "sm_weibull_ph_gamma"))+ +bayesplot::mcmc_dens_overlay(my_fitpop_df, pars=my_pars)+ theme_minimal() #' =========================================================== -#' +#' #' II. CONVERGENCE -#' +#' #' =========================================================== #' Checking that Rhat<1.05 #' ------------------------------------------------------------\ -#' Using {posterior} #' see https://cran.r-project.org/web/packages/bayesplot/vignettes/visual-mcmc-diagnostics.html -posterior::summarise_draws(my_fit_df) #' Using {bayesplot} rhats <- bayesplot::rhat(mp@results) @@ -203,9 +222,9 @@ bayesplot::mcmc_trace(my_fit_df, pars = my_pars)+ #' =========================================================== -#' +#' #' III. GOODNESS OF FIT -#' +#' #' =========================================================== # Log Likelihood @@ -230,14 +249,40 @@ mp@results$loo() #' =========================================================== -#' +#' #' IV. PREDICTIONS -#' +#' #' Overlaying KM and posterior survival curves -#' See example: -#' https://stablemarkets.netlify.app/post/post2/specifying-accelerated-failure-time-models-in-stan/ -#' -#' +#' See example: +#' https://stablemarkets.netlify.app/post/post2/specifying-accelerated-failure-time-models-in-stan/ +#' +#' #' =========================================================== +# Calculate the survival distribution for each subject at each desired timepoint +# To get different quantities change the `pweibullPH` to the desired distribution +# function e.g. hweibullPH / HweibullPH + +zparms<-my_fitpop_df |> + pivot_longer(cols = 1:3, names_to = "parms", values_to = "value") |> + group_by(parms) |> + tidybayes::median_qi() |> + ungroup() + +jdat<-DataJoint( + subject=DataSubject(data=bc1, subject="ID", arm="group", study="study"), + survival=DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) +) +set.seed(13579) +covs <- data.frame(ID = bc1$ID, trt=bc1$group) +s1 <- simsurv(dist="exponential", + x=covs, betas=c(trt=0), + lambdas = zsurv$lambda[1], maxt = max(bc1$recyrs)) + +survfit2(Surv(eventtime, status) ~ 1, data = s1) |> + ggsurvfit(linewidth = 1) + + add_confidence_interval() + + add_risktable() + + add_quantile(y_value = 0.6, color = "gray50", linewidth = 0.75) + + scale_ggsurvfit() diff --git a/vignettes/survival_standalone.Rmd b/vignettes/survival_standalone.Rmd index cd9ef1d77..ec5da2168 100644 --- a/vignettes/survival_standalone.Rmd +++ b/vignettes/survival_standalone.Rmd @@ -192,10 +192,17 @@ The following distributional assumptions for the baseline hazard are currently i The following table shows the location and ancillary parameter with their default priors. -```{r setup, message=FALSE, warning=FALSE} +```{r setup, eval=TRUE, echo=FALSE, message=FALSE, warning=FALSE} + +library(tidyverse) library(knitr) library(kableExtra) library(flexsurv) +library(jmpost) +library(posterior) +library(tidybayes) +library(bayesplot) + ``` ```{r distributiontable, echo=FALSE} @@ -214,7 +221,7 @@ ztab <- data.frame( # Create table knitr::kable(ztab, escape = F, - caption = 'Table example', + caption = 'Table 1. Location and shape parameters for the distributions implemented in jmpost', col.names = c("Distribution", "Location (or Scale)", "Shape")) ``` @@ -230,13 +237,14 @@ In the following, we run a simple example to present the features of **jmpost**. The 'bc' dataset from [**flexsurv**](https://chjackson.github.io/flexsurv/) is used. It contains data for 686 patients with primary node positive breast cancer. The right-censored time-to-event variable `recyrs` represents the time (in years) of death or cancer recurrence when `censrec` is 1, or right censoring when `censrec` is 0. The covariate `group` is a factor representing a prognostic score, with 3 levels: "Good" (the reference), "Medium" and "Poor". Showing the first 6 and the last 6 rows, the dataset looks like this: + ```{r, eval=TRUE, echo=TRUE} rbind(head(bc), tail(bc)) ``` The call to fit an exponential PH model in **jmpost** would be as follow: -```{r, eval=FALSE, echo=TRUE} +```{r, eval=TRUE, echo=TRUE} jm<-JointModel(survival= SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) @@ -247,7 +255,8 @@ jdat<-DataJoint( survival = DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) ) -mp<-sampleStanModel(jm, data=jdat, iter_warmup=4000, iter_sampling=1000, chains=4) +mp<-sampleStanModel(jm, data=jdat, iter_warmup=4000, + iter_sampling=1000, chains=4, refresh=0) vars<-c("sm_exp_lambda", "beta_os_cov") mp@results$summary(vars) @@ -255,40 +264,74 @@ mp@results$summary(vars) Details about the parameters and functions are available in the [Model Fitting](https://genentech.github.io/jmpost/main/articles/model_fitting.html). -### 3.2 Default outputs +### 3.2 Descriptive outputs -The default output reports statistics for one or more sampler chains over all model parameters and quantities of interest. -The statistics reported include both summary statistics of the estimates and diagnostic statistics on the sampler chains, reported in the following order: -- mean: sample mean, -- median: sample median, -- sd: sample standard deviation, -- q5, q95: 5th and 95th percentiles of the posterior distribution, -- rhat: +The most efficient way of extracting relevant outputs from the MCMC samples is to use the **posterior** package. +In the below snippet, after having reformatted the model results with `posterior::as_draws_df(mp@results)`, all samples across chains are available in `my_fitall_df`. +The **posterior** package can then be used to extract the relevant quantities. -```{r} +```{r, eval=TRUE, echo=TRUE} +#' ------------------------------------------------------------\ +my_fitall_df <- posterior::as_draws_df(mp@results) +my_pars<-c("sm_exp_lambda", "beta_os_cov[1]", "beta_os_cov[2]") +my_fitpop_df<-posterior::subset_draws(my_fitall_df, variable=my_pars) -#' Convert the samples in a df #' ------------------------------------------------------------\ -mp@results$summary(vars) +posterior::summarise_draws(my_fitpop_df) -my_fit_df <- posterior::as_draws_df(mp@results) -my_pars<-c("sm_exp_lambda", "beta_os_cov[1]", "beta_os_cov[2]") +``` +Traceplots (a.k.a. caterpillar plots), Rhat, effective sample size (ESS) and autocorrelation in the samples have to be examined for convergence to be considered as acceptable. -#' Summarize the posterior samples -#' ------------------------------------------------------------\ -#' Using {posterior} -posterior::summarise_draws(my_fit_df) +To this extent a [recommendation](https://cran.r-project.org/web/packages/bayesplot/vignettes/visual-mcmc-diagnostics.html#effective-sample-size) of the Stan development team is to study these measures of convergence using the **bayesplot** package. + +Other interesting quantities, such as posterior quantiles or highest density interval (HDI) for any given parameter can also be extracted using the **tidybayes** package. + +In the following code, we extract various measures of uncertainty associated with the mean or the median of the exponential rate (`sm_exp_lambda`). + +```{r, eval=TRUE, echo=TRUE} +#' For each parameter, it is possible to extract various quantities: +#' mean_hdci(), median_hdci(), etc ... from [median|mean|mode]_[qi|hdi] +#' see: ggdist:: ?mean_qi +my_fitpop_df %>% + tidybayes::spread_rvars(sm_exp_lambda) %>% + tidybayes::mean_hdci() +my_fitpop_df %>% + tidybayes::spread_rvars(sm_exp_lambda) %>% + tidybayes::mean_qi() + +#' Median (and associated uncertainty expressed as lower and upper bounds for +#' pmf containing 50%, 89%, 90% of the distribution density +#' = e.g. 89% credibility interval for the median) +#' for sm_exp_lambda across all chains +my_fitpop_df %>% + tidybayes::spread_rvars(sm_exp_lambda) %>% + tidybayes::median_qi(.width = c(.50, .89, .95)) ``` - +Finally, the posterior distributions for any given model parameter (across chains or overall) can be easily displayed graphically using the **bayesplot** package. + +```{r, eval=TRUE, echo=TRUE} +bayesplot::mcmc_areas(my_fitpop_df, pars = my_pars, prob = 0.8)+ + theme_minimal() +bayesplot::mcmc_dens_overlay(my_fitpop_df, pars=my_pars)+ + theme_minimal() +``` + + ### 3.3 Goodness-of-fit evaluation + ### 3.4 Observed vs. fitted survival +In this section, we illustrate how to overlay the fitted survival curves for each patient respectively and the Kaplan-Meier curve for the studied sample. + +We start by extracting the individual location parameter estimate. + + diff --git a/vignettes/trash.R b/vignettes/trash.R new file mode 100644 index 000000000..575f2daf4 --- /dev/null +++ b/vignettes/trash.R @@ -0,0 +1,46 @@ + From dc4b6c2708a72a5aecbd06b0149e18684943bbde Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Mon, 24 Jun 2024 18:46:44 +0200 Subject: [PATCH 09/15] Annie Ross - Limehouse blues --- vignettes/statistical-specification.Rmd | 2 +- vignettes/survival_standalone.Rmd | 336 --------------------- vignettes/survivalonly-1-statsspecs.Rmd | 378 ++++++++++++++++++++++++ 3 files changed, 379 insertions(+), 337 deletions(-) delete mode 100644 vignettes/survival_standalone.Rmd create mode 100644 vignettes/survivalonly-1-statsspecs.Rmd diff --git a/vignettes/statistical-specification.Rmd b/vignettes/statistical-specification.Rmd index 7de19fe4d..acf7c3fbc 100644 --- a/vignettes/statistical-specification.Rmd +++ b/vignettes/statistical-specification.Rmd @@ -9,8 +9,8 @@ output: link-citations: true vignette: > %\VignetteIndexEntry{Statistical Specifications} - %\VignetteEngine{knitr::rmarkdown} %\VignetteEncoding{UTF-8} + %\VignetteEngine{knitr::rmarkdown} editor_options: chunk_output_type: console --- diff --git a/vignettes/survival_standalone.Rmd b/vignettes/survival_standalone.Rmd deleted file mode 100644 index 1251d2b91..000000000 --- a/vignettes/survival_standalone.Rmd +++ /dev/null @@ -1,336 +0,0 @@ ---- -title: "01. Survival models" -subtitle: "Part 1. Statistical specifications" -package: jmpost -output: rmarkdown::html_vignette -vignette: > - %\VignetteIndexEntry{Model Fitting} - %\VignetteEncoding{UTF-8} - %\VignetteEngine{knitr::rmarkdown} -editor_options: - chunk_output_type: console - markdown: - wrap: 72 ---- - -```{r, include=FALSE} -knitr::opts_chunk$set(echo = TRUE, collapse = TRUE) -``` - -## Scope of this document - -This document describes how to analyze survival data using parametric -survival models implemented in the **jmpost** R package. It is organized -in 4 sections: - -1. Introduction - -2. Survival model framework - -3. Fitting a simple survival model in **jmpost** - -4. Comparing with **flexsurv** and **survstan** outputs - -## 1. Introduction - -Survival (or time-to-event, or failure time) analysis is concerned with -the study of survival times and factors influencing them. - -There are 3 common approaches to modelling survival data: - -1. Models of the instantaneous rate of the event (known as the hazard) - as a function of time taken as a continuous variable. This includes - the well-known class of proportional hazards (PH) regression models. - -2. Models the event time itself, again considering time as a continuous - variable, including the accelerated failure time (AFT) models. - -3. Models of the occurrence of event when time is taken as a discrete - variable, specifically the additive hazard regression (AHR) model. - -In the current version of **jmpost**, we focus on approach 1., and -specifically on PH models, implemented in a Bayesian framework. - -Proportional hazard (PH) models play an important role in analyzing -survival and rely on a key assumption: the hazard ratio (HR) comparing -any two levels of a covariate is constant over time. The Cox PH model is -most popular for two reasons: (a) no assumption is required about the -probability distribution of survival times, and (b) it fits the data -reasonably well no matter which parametric model is appropriate. - -In contrast, distributional assumption is required for a fully -parametric PH model (Kalbfleisch and Prentice 2002 :: The Statistical -Analysis of Failure Time Data. John Wiley & Sons, New Jersey; Lawless -2002 :: Statistical Models and Methods for Lifetime Data. John Wiley & -Sons, New Jersey (2002)). When the distribution is selected wisely, -parametric models lead to more efficient (i.e. smaller standard errors) -estimates than Cox's model (Collett 2003 :: Modelling Survival Data in -Medical Research. Chapman and Hall/CRC, Florida). - -Moreover, the use of Cox PH in joint modeling of time-to-event and -longitudinal data (Wulfsohn and Tsiatis 1997 :: A joint model for -survival and longitudinal data measured with errror. Biometrics. 53, -330--339) usually leads to an underestimation of the parameter estimates -standard errors (Hsieh et al. 2006 :: Joint modeling of survival and -longitudinal data: Likelihood approach revisited. Biometrics. 62, -1037--1043; Rizopoulos 2012 :: Joint Models for Longitudinal and -Time-to-Event Data With Applications in R. Chapman and Hall/CRC, -Florida). Therefore, most methods for joint modeling are based on -parametric response distributions (Hwang and Pennell 2014 :: -Semiparametric bayesian joint modeling of a binary and continuous -outcome with applications in toxicological risk assessment. Stat. Med. -33, 1162--1175). - -Bayesian inference offers the opportunity - -- to make probability statements about parameters, - -- to handle hierarchical structures naturally, - -- to have good statistical properties when dealing with small samples, and - -- to quantify uncertainty in predicted quantities easily. - -All these properties are convenient for joint models, but also -for survival models taken separately. - -**jmpost** is written in Stan, a high-level language (itself written in -a C++) for Bayesian modeling and inference that primarily uses a version -of the No-U-Turn sampler (NUTS) (Hoffman & Gelman, 2014 :: Hoffman, M. -D., & Gelman, A. (2014). The No-U-turn sampler: Adaptively setting path -lengths in Hamiltonian Monte Carlo. Journal of Machine Learning -Research, 15(47), 1593-1623) to obtain posterior samples given a -user-specified model and data. - -Although Stan is an extremely flexible and powerful software for -statistical modelling, it is neither user-friendly nor easy to learn. To -remove this hurdle, we propose **jmpost** as a layer on top of Stan to -facilitate the encoding of PH models, either stand-alone, or integrated -in joint models. - -## 2. Survival model framework - -Let $T^*_i$ denote a continuous non-negative random variable -representing survival time for individual $i$ (with $i=1, ..., n$). - -In reality, the event time $T^*_i$ may not be observed due to -right-censoring; for instance, the event may occur after the end of the -clinical study, denoted $\tau_f$. We define the outcome as the pair: -$T_i$ being the observed event or censoring time (with $T_i>0$) and -$d_i \in \{0,1\}$, an indicator taking value 0 in case of right -censoring (i.e. $T^*_i>\tau_f$), or value 1 if the event is observed -(i.e. $T^*_i=T_i$). - -Three key quantities form the likelihood function for survival models: -the hazard rate, the cumulative hazard, and the survival probability. - -The survival function $S(t, \psi_i)$ gives the probability that the -event happens to individual $i$ after time t, where $\psi_i$ represent -the individual parameters. -$$ -S(t, \psi_i) = P(T_i>t; \psi_i) -$$ - -The hazard function $h(t, \psi_i)$ is the instantaneous rate of occurrence of the event for individual $i$ at time $t$, given that the event has not already occurred. Mathematically, it is defined as: -$$ -h(t, \psi_i) = \displaystyle \lim_{dt \to 0} \displaystyle \frac{P(t \le T_i < t+dt \mid T_i > t)}{dt} -$$ -where $dt$ is a small time interval. - -This is equivalent to: -$$ -h(t, \psi_i)= - \frac{d}{dt} \log S(t, \psi_i) -$$ -Knowing the hazard function gives access to the survival function. - -The cumulative hazard is defined as: -$$ -H(a, b, \psi_i)=\int_{a}^{b} h(t, \psi_i) \; dt -$$ - -which implies that: -$$ -S(t, \psi_i) = \exp(-H(0, t, \psi_i)) -$$ - -The log-likelihood function in presence of right-censoring measures the risk of experiencing the event at any time point $t$, conditionally on that individual $i$ has in fact survival until that time point; if s/he has not survived, then the probability of experiencing the event again is 0: -$$ -log \mathcal{L}=\sum_{i = 1}^{n} \left[ d_i \log h(t, \psi_i) + \log S(t, \psi_i) \right] -$$ - -When formulating a parametric survival model, we need to specify the form of the probability distribution assumed to describe the underlying uncertainty in the observed times. - -In general terms, we can specify the vector of relevant parameters as $\theta = (μ(x), \alpha(x))$. In this notation, consistent with **flexsurv**, we consider: - -- a vector of potential covariates $x$ (e.g., treatment group, age, or sex), - -- a *location* parameter $\mu(x)$, which indicates the *mean* or the *scale* of the probability distribution, - -- and a (set of) ancillary parameters $\alpha(x)$, which describe the *shape* or *variance* of the distribution. - -While it is possible for both $\mu$ and $\alpha$ to explicitly depend on the covariates $x$, usually the formulation is simplified to assume that these only affect directly the location parameter. - -To parameterize the effect of covariates on the location parameter, a generalized linear formulation is employed: -$$ -g(\mu_i)=\beta_0+\sum_{k = 1}^{K} \beta_k x_ik -$$ -The function $g(.)$ is typically the logarithm, but alternative transformations such as square-root or Box-Cox could also be considered. - -We model the hazard of event for individual $i$ at time $t$ using the regression model: -$$ -h(t, \psi_i)=h_0(t) \exp(\beta_0+\sum_{k = 1}^{K} \beta_k x_{ik}) -$$ -where $h_0(t)$ is the baseline hazard (i.e. the hazard for an individual with the covariates set equals to zero) at time $t$, and the terms in $exp(.)$ denotes the linear predictors evaluated for individual $i$ at time $t$. - -The following distributional assumptions for the baseline hazard are currently implemented in the **jmpost** package: - -1- Exponential - -2- Weibull - -3- Log-logistic - -The following table shows the location and ancillary parameter with their default priors. - -```{r setup, eval=TRUE, echo=FALSE, message=FALSE, warning=FALSE} - -library(tidyverse) -library(knitr) -library(kableExtra) -library(flexsurv) -library(jmpost) -library(posterior) -library(tidybayes) -library(bayesplot) - -``` - -```{r distributiontable, echo=FALSE} -ztab <- data.frame( - Dist = c("\\( \\ T_i \\sim \\exp(\\mu_i) \\)", - "\\( \\ T_i \\sim Weibull(\\mu_i, \\alpha) \\)", - "\\( \\ T_i \\sim logLogistic(\\mu_i, \\alpha) \\)"), - Loca = c("\\( \\ Rate: \\mu_i=\\exp(\\beta_0+\\sum_{k = 1}^{K} \\beta_k x_{ik}) \\)", - "\\( \\ Scale: \\mu_i= (idem) \\)", - "\\( \\ Rate: \\mu_i= (idem) \\)"), - Shap = c("\\( NA \\)", - "\\( \\ Shape: \\alpha \\sim \\gamma(0.1, 0.1) \\)", - "\\( \\ Shape: \\alpha \\sim \\gamma(0.1, 0.1) \\)") -) - -# Create table -knitr::kable(ztab, - escape = F, - caption = 'Table 1. Location and shape parameters for the distributions implemented in jmpost', - col.names = c("Distribution", "Location (or Scale)", "Shape")) -``` - -The models implemented in **jmpost** all have a PH parameterization. - - -## 3. Fitting a simple survival model in jmpost - -### 3.1. Call - -In the following, we run a simple example to present the features of **jmpost**. - -The 'bc' dataset from [**flexsurv**](https://chjackson.github.io/flexsurv/) is used. It contains data for 686 patients with primary node positive breast cancer. The right-censored time-to-event variable `recyrs` represents the time (in years) of death or cancer recurrence when `censrec` is 1, or right censoring when `censrec` is 0. The covariate `group` is a factor representing a prognostic score, with 3 levels: "Good" (the reference), "Medium" and "Poor". - -Showing the first 6 and the last 6 rows, the dataset looks like this: - -```{r, eval=TRUE, echo=TRUE} -rbind(head(bc), tail(bc)) -``` - -The call to fit an exponential PH model in **jmpost** would be as follow: - -```{r, eval=TRUE, echo=TRUE} -jm<-JointModel(survival= - SurvivalExponential(lambda=prior_lognormal(log(0.06), 1))) - -bc1<-bc %>% - mutate(ID=as.character(1:n()), study=1) -jdat<-DataJoint( - subject = DataSubject(data=bc1, subject="ID", arm="group", study="study"), - survival = DataSurvival(data=bc1, formula=Surv(recyrs, censrec)~group) -) - -mp<-sampleStanModel(jm, data=jdat, iter_warmup=4000, - iter_sampling=1000, chains=4, refresh=0) -vars<-c("sm_exp_lambda", "beta_os_cov") -mp@results$summary(vars) - -``` - -Details about the parameters and functions are available in the [Model Fitting](https://genentech.github.io/jmpost/main/articles/model_fitting.html). - -### 3.2 Descriptive outputs - -The most efficient way of extracting relevant outputs from the MCMC samples is to use the **posterior** package. -In the below snippet, after having reformatted the model results with `posterior::as_draws_df(mp@results)`, all samples across chains are available in `my_fitall_df`. - -The **posterior** package can then be used to extract the relevant quantities. - -```{r, eval=TRUE, echo=TRUE} -#' ------------------------------------------------------------\ -my_fitall_df <- posterior::as_draws_df(mp@results) -my_pars<-c("sm_exp_lambda", "beta_os_cov[1]", "beta_os_cov[2]") -my_fitpop_df<-posterior::subset_draws(my_fitall_df, variable=my_pars) - -#' ------------------------------------------------------------\ -posterior::summarise_draws(my_fitpop_df) - -``` - -Traceplots (a.k.a. caterpillar plots), Rhat, effective sample size (ESS) and autocorrelation in the samples have to be examined for convergence to be considered as acceptable. - -To this extent a [recommendation](https://cran.r-project.org/web/packages/bayesplot/vignettes/visual-mcmc-diagnostics.html#effective-sample-size) of the Stan development team is to study these measures of convergence using the **bayesplot** package. - -Other interesting quantities, such as posterior quantiles or highest density interval (HDI) for any given parameter can also be extracted using the **tidybayes** package. - -In the following code, we extract various measures of uncertainty associated with the mean or the median of the exponential rate (`sm_exp_lambda`). - -```{r, eval=TRUE, echo=TRUE} -#' For each parameter, it is possible to extract various quantities: -#' mean_hdci(), median_hdci(), etc ... from [median|mean|mode]_[qi|hdi] -#' see: ggdist:: ?mean_qi -my_fitpop_df %>% - tidybayes::spread_rvars(sm_exp_lambda) %>% - tidybayes::mean_hdci() -my_fitpop_df %>% - tidybayes::spread_rvars(sm_exp_lambda) %>% - tidybayes::mean_qi() - -#' Median (and associated uncertainty expressed as lower and upper bounds for -#' pmf containing 50%, 89%, 90% of the distribution density -#' = e.g. 89% credibility interval for the median) -#' for sm_exp_lambda across all chains -my_fitpop_df %>% - tidybayes::spread_rvars(sm_exp_lambda) %>% - tidybayes::median_qi(.width = c(.50, .89, .95)) - -``` - -Finally, the posterior distributions for any given model parameter (across chains or overall) can be easily displayed graphically using the **bayesplot** package. - -```{r, eval=TRUE, echo=TRUE} -bayesplot::mcmc_areas(my_fitpop_df, pars = my_pars, prob = 0.8)+ - theme_minimal() -bayesplot::mcmc_dens_overlay(my_fitpop_df, pars=my_pars)+ - theme_minimal() -``` - - -### 3.3 Goodness-of-fit evaluation - - - -### 3.4 Observed vs. fitted survival - -In this section, we illustrate how to overlay the fitted survival curves for each patient respectively and the Kaplan-Meier curve for the studied sample. - -We start by extracting the individual location parameter estimate. - - - - diff --git a/vignettes/survivalonly-1-statsspecs.Rmd b/vignettes/survivalonly-1-statsspecs.Rmd new file mode 100644 index 000000000..7344dd3b4 --- /dev/null +++ b/vignettes/survivalonly-1-statsspecs.Rmd @@ -0,0 +1,378 @@ +--- +title: "01. Survival models" +subtitle: "Part 1. Statistical specifications" +package: jmpost +output: rmarkdown::html_vignette +vignette: > + %\VignetteIndexEntry{Model Fitting} + %\VignetteEncoding{UTF-8} + %\VignetteEngine{knitr::rmarkdown} +editor_options: + chunk_output_type: console + markdown: + wrap: 72 +--- + +```{r, include=FALSE} +knitr::opts_chunk$set(echo = TRUE, collapse = TRUE) +``` + +## Scope of this document + +This document describes how to analyze survival data using parametric +survival models implemented in the `jmpost` R package. It is organized +in 4 sections: + +- Introduction + +- Modeling framework + +- Implementation + +## 1. Introduction + +Survival analysis, also referred to as time-to-event or failure time +analysis, investigates the duration until one or more events of interest +occur and the factors influencing these durations. Comprehensive +introductions to survival analysis are provided by Kalbfleisch and +Prentice (2002), Collett (2003), and Hosmer et al. (2008). + +Three predominant approaches to modeling survival data are commonly +employed: + +1. Hazard Rate Models: These models describe the instantaneous rate of + the event (the hazard) as a function of time, treated as a + continuous variable. This category includes the widely used class of + proportional hazards (PH) regression models. + +2. Event Time Models: These models directly analyze the event time + itself, also treating time as a continuous variable. The accelerated + failure time (AFT) models fall under this category. + +3. Discrete Time Models: These models analyze the occurrence of events + when time is considered as a discrete variable, with the additive + hazard regression (AHR) model being a specific example. + +In the current version of the `jmpost` package, we focus on the first +approach, specifically on PH models within a Bayesian framework. + +Proportional hazards (PH) models are pivotal in survival analysis and +rely on the key assumption that the hazard ratio (HR) comparing any two +levels of a covariate remains constant over time. The Cox PH model is +the most popular among these models for two primary reasons: (a) it does +not require assumptions about the probability distribution of survival +times, and (b) it generally fits data well across various parametric +models. + +In contrast, fully parametric PH models require a distributional +assumption (Kalbfleisch and Prentice 2002; Lawless 2002). When the +appropriate distribution is selected, parametric models can provide more +efficient estimates, reflected in smaller standard errors compared to +the Cox model (Collett 2003). Moreover, using the Cox PH model in joint +modeling of time-to-event and longitudinal data (Wulfsohn and Tsiatis +1997) often leads to underestimation of standard errors of parameter +estimates (Hsieh et al. 2006; Rizopoulos 2012). Consequently, most joint +modeling methods are based on parametric response distributions (Hwang +and Pennell 2014). + +Furthermore, the application of Cox proportional hazards (PH) models in +joint modeling of time-to-event and longitudinal data often results in +the underestimation of the standard errors of parameter estimates +(Wulfsohn and Tsiatis 1997; Hsieh et al. 2006; Rizopoulos 2012). As a +result, many methods for joint modeling are predicated on parametric +response distributions (Hwang and Pennell 2014). + +Bayesian inference offers several advantages: + +- The ability to make probability statements about parameters. + +- Natural handling of hierarchical structures. + +- Robust statistical properties, particularly with small sample sizes. + +- The capacity to easily quantify uncertainty in predicted quantities. + +These properties are highly advantageous for joint models and are +equally beneficial when applied to survival models independently. + +`jmpost` is developed in Stan, a high-level language (itself implemented +in C++) designed for Bayesian modeling and inference. Stan primarily +utilizes a variant of the No-U-Turn sampler (NUTS) (Hoffman & Gelman, +2014) to generate posterior samples based on a user-specified model and +data. + +While Stan is an exceptionally flexible and powerful tool for +statistical modeling, it can be challenging to learn and is not +inherently user-friendly. To address this barrier, we introduce `jmpost` +as an additional layer atop Stan, simplifying the encoding of +proportional hazards (PH) models. This includes both stand-alone PH +models and those integrated within joint models. + +## 2. Modeling framework + +### 2.1. Distribution of time-to-event data + +Let $T$ denote a continuous non-negative random variable representing +survival time. This variable can be specified by its density function +$f(t)$ and cumulative distribution function $F(t)$. The hazard function, +defined as + +$$ +h(t) = \lim_{\Delta \to 0} \frac{P(t < T \leq t + \Delta \mid T > t)}{\Delta} +$$ + +plays a central role in modeling the time to event. The hazard function +represents the risk of an event occurring immediately after time $t$, +given that no event has occurred up to time $t$. From this definition, +we can derive that $h(t) = \frac{f(t)}{S(t)}$, where $S(t) = 1 - F(t)$ +is the survival function, representing the probability of no event +occurring until time $t$. + +From the hazard function, we can define the cumulative hazard function +as + +$$ +H(t) = \int_0^t h(\tau) \, d\tau +$$ + +which is related to the survival function by $S(t) = \exp(-H(t))$. The +relationships between $h(t)$, $H(t)$, $f(t)$, and $S(t)$ constitute the +fundamental formulas that represent key concepts in survival modeling. + +In practice, the exact event time may not be observed due to right +censoring, such as when the event occurs after the conclusion of a +clinical trial. Formally, let $T_i^*$ be the true event time and $C_i$ +be the censoring time (e.g., the end of the study). We observe +$T_i = \min(T_i^*, C_i)$. To distinguish censored observations, we use +an event indicator $d_i$, which is 0 for right censoring ($T_i^* > C_i$) +and 1 if the event is observed ($T_i = T_i^*$). Thus, the observed +outcome is defined by the pair $\{T_i, d_i\}$, where $T_i > 0$. + +### 2.2. Parametric model + +Parametric time-to-event models are constructed by specifying the +outcome distribution. For instance, suppose $T$ follows an exponential +distribution: + +$$ T \sim \text{exp}(\lambda) \quad \text{with} \; \lambda > 0, $$ + +with + +$$ f(t) = \lambda \cdot \exp(-\lambda t) \quad \text{and} \quad F(t) = 1 - \exp(-\lambda t). $$ + +This leads to + +$$ S(t) = 1 - F(t) = \exp(-\lambda t). $$ + +Using $h(t) = \frac{f(t)}{S(t)}$, we get $h(t) = \lambda$. The hazard +function for the exponential distribution is constant. + +However, the exponential distribution is often too restrictive. In +principle, any positive continuous distribution (or transformation to +obtain such) can be used for the outcome. One of the most commonly used +distributions is the Weibull distribution, a two-parameter model +flexible enough to characterize both monotonic increasing and decreasing +hazard rates over time. Different parameterizations exist for this +distribution. Within `jmpost`, the survival and hazard functions are +implemented using the following parameterization: + +$$ S(t) = \exp(-(\lambda t)^\gamma) $$ + +$$ h(t) = \lambda \gamma \cdot t^{\gamma-1} $$ + +where $\gamma > 0$ is the shape parameter and $\lambda > 0$ is the scale +parameter. The density function can be derived from +$f(t) = h(t) \cdot S(t)$. + +Additionally, a log-logistic distribution can also be considered. Its +hazard and survival functions are: + +$$ S(t) = \frac{1}{1 + (t/b)^a} $$ + +$$ h(t) = \frac{(a/b) \cdot (t/b)^{a-1}}{1 + (t/b)^a} $$ + +where $a$ is the shape parameter and $b$ is the scale parameter. + +To summarize, the parameters involved in each type of parametric +survival model are recapitulated in [Table 1](#table1). + + Table 1. Parameters associated with each survival +model + +| Model | Parameter | Variable name | Interpretation | Default prior | +|---------------|---------------|---------------|---------------|---------------| +| Exponential | $\lambda$ | `sm_exp_lambda` | Time invariant hazard rate | xxx | +| Weibull | $\gamma$ | `sm_weibull_ph_gamma` | Shape | xxx | +| | $\lambda$ | `sm_weibull_ph_lambda` | Scale | xxx | +| Log-logistic | $a$ | `sm_loglogis_a` | Shape | xxx | +| | $b$ | `sm_loglogis_b` | Scale | xxx | + +### 2.3. Covariate model + +In many cases, additional characteristics of the individuals, such as +age, sex, tumor stage, etc., are known. These characteristics are +referred to as covariates. Let $X_i$ denote the $p \times 1$ vector of +values from the covariate matrix $X$ for individual $i$, and let $\beta$ +be a $p \times 1$ vector of regression coefficients. It is plausible to +assume that $X$ influences the shape, scale, or both parameters of the +model. However, a common approach is to assume that $X$ affects only the +scale parameter. The typical formulation for this relationship is: + +$$ +\log(\mu_i) = X_i^T \beta +$$ + +To ensure identifiability, we assume that the design vector $X_i$ does +not include a constant term; that is, no intercept is included in the +above equation. + +Various regression models can be fitted, such as proportional hazard +(PH) models, accelerated failure time (AFT) models, proportional odds +(PO) models, etc. Currently, `jmpost` implements only PH regression +models. PH models are defined as: + +$$ +h_i(t) = h_0(t) \cdot \exp(X_i^T \beta) +$$ + +where $h_0(t)$ is the baseline hazard function. + +The hazard ratio (HR) quantifies the relative increase in the hazard +associated with a unit increase in the relevant covariate, $X_i$, while +holding all other covariates in the model constant. + +### 2.4. Log-likelihood + +We can specify the relevant parameter(s) as $\theta$. In the case of the +exponential distribution, $\theta = \lambda$. For other distributions, +$\theta = (\mu, \alpha)$, where $\mu$ represents the location or scale +parameter, and $\alpha$ describes the shape or variance of the +distribution. The objective of the statistical analysis is the +estimation of $\theta$, which can then be used to obtain estimates for +all relevant quantities (e.g., the survival function). + +Based on the observed outcomes $\{T_i, d_i\}$ for $i = 1, \ldots, n$, +the likelihood function can be written as: + +$$ +L(\theta) = \prod_{i=1}^{n} f(T_i)^{d_i} \cdot S(T_i)^{1 - d_i} \cdot g(d_i) +$$ + +where $g(d_i)$ is the density function of $d_i$. We assume that $C_i$ +and consequently $d_i$ are independent of $T_i$. This type of censoring +is known as non-informative censoring. Hence, we will ignore the +$g(d_i)$ part afterwards. + +The maximum likelihood estimator maximizes the above log-likelihood +function. Given that $f(t) = h(t) \cdot S(t)$, the log-likelihood can +therefore be expressed as: + +$$ +\log L(\theta) = \sum_{i=1}^{n} \left[ d_i \cdot \log h(T_i) + \log S(T_i) \right] +$$ + +Since $H(t) = -\log S(t)$, the log-likelihood can also be expressed as: + +$$ +\log L(\theta) = \sum_{i=1}^{n} \left[ d_i \cdot \log h(T_i) - H(T_i) \right] +$$ + +### 2.5. Bayesian inference + +In a full Bayesian setting, the parameters are modeled directly using a +prior probability distribution, which is updated by the observed data +into a posterior distribution. The posterior distribution is the focus +of the inferential process. Therefore, when using a Bayesian framework, +the model must be completed by specifying suitable prior distributions +for the $\theta$ parameters. + +Within `jmpost`, all parameters have default priors assigned to them, +but users can explicitly specify the priors if they wish. The default +choice of prior distribution for the regression coefficients is +$N(\mu_\beta = 0, \sigma_\beta = 2)$, defined on the log scale. This +amounts to specifying a "minimally informative" prior on the regression +coefficients that determine the location parameter---in other words, we +are not including strong prior information in this aspect of our model. +The observed data (and the censoring structure) will primarily drive the +update to the posterior distribution. + +There are several choices of prior distributions for the model +parameters related to the baseline hazard (see [Table 1](#table1)). In +theory, any distribution defined in the $(0, +\infty)$ domain would be +viable as a prior distribution; however, the most common choices +include: + +- A half-normal, half-t, half-Cauchy, or exponential prior + distribution for the Weibull shape parameter. +- A half-normal, half-t, half-Cauchy, or exponential prior + distribution for the log-logistic scale parameter. + +### 2.6. Estimation + +The `jmpost` package is built on top of the `cmdstanr` R package (Stan +Development Team, 2019), the most advanced R interface for Stan. Stan, a +C++ library, provides a powerful platform for statistical modeling +(Carpenter et al., 2017) and uses the No-U-Turn Sampler (NUTS), a +specific implementation of Hamiltonian Monte Carlo (HMC) (Hoffman and +Gelman, 2014). Models in `jmpost` are written in the Stan programming +language, translated into C++ code, and compiled at runtime. + +Estimation in `jmpost` relies on full Bayesian inference. HMC, a form of +Markov chain Monte Carlo (MCMC), uses gradient information of the log +posterior to efficiently sample from the posterior space. + +Leveraging `cmdstanr`, `jmpost` allows users to control various aspects +of the estimation process, including the number of MCMC chains, the +number of warm-up and sampling iterations, and the number of computing +cores used. + +## 3. Implementation + +The design of `jmpost` is modular, with distinct sets of functions +tailored to specific objectives. These functions can be broadly +categorized into three main groups: **Data Preparation**, **Model +Fitting and Assessment**, and **Sensitivity Analysis and Predictions**, +as illustrated schematically in Figure 1. + +![Figure 1.](path/to/figure1.png) + +## 4. References + +### References + +- Baio, G. (2020). survHE: Survival analysis for health economic + evaluation and cost-effectiveness modeling. *Journal of Statistical + Software*, doi: + [10.18637/jss.v095.i14](https://doi.org/10.18637/jss.v095.i14). +- Carpenter, B., Gelman, A., Hoffman, M. D., et al. (2017). Stan: A + probabilistic programming language. *Journal of Statistical + Software*, doi: + [10.18637/jss.v076.i01](https://doi.org/10.18637/jss.v076.i01). +- Collett, D. (2003). *Modelling Survival Data in Medical Research*. + Chapman and Hall/CRC, Florida. +- Hoffman, M. D., & Gelman, A. (2014). The No-U-turn sampler: + Adaptively setting path lengths in Hamiltonian Monte Carlo. *Journal + of Machine Learning Research*, 15, 1593-1623. +- Hosmer, D. W., Lemeshow, S., & May, S. (2008). *Applied Survival + Analysis: Regression Modeling of Time-to-Event Data*. John Wiley & + Sons, New Jersey. +- Hsieh, F., Tseng, Y.-K., & Wang, J.-L. (2006). Joint modeling of + survival and longitudinal data: Likelihood approach revisited. + *Biometrics*, 62, 1037-1043. +- Hwang, W., & Pennell, M. L. (2014). Semiparametric Bayesian joint + modeling of a binary and continuous outcome with applications in + toxicological risk assessment. *Statistics in Medicine*, 33, + 1162-1175. +- Jackson, C. (2016). flexsurv: A platform for parametric survival + modeling in R. *Journal of Statistical Software*, doi: + [10.18637/jss.v070.i08](https://doi.org/10.18637/jss.v070.i08). +- Kalbfleisch, J. D., & Prentice, R. L. (2002). *The Statistical + Analysis of Failure Time Data*. John Wiley & Sons, New Jersey. +- Lawless, J. F. (2002). *Statistical Models and Methods for Lifetime + Data*. John Wiley & Sons, New Jersey. +- Rizopoulos, D. (2012). *Joint Models for Longitudinal and + Time-to-Event Data With Applications in R*. Chapman and Hall/CRC, + Florida. +- Wulfsohn, M. S., & Tsiatis, A. A. (1997). A joint model for survival + and longitudinal data measured with error. *Biometrics*, 53, + 330-339. From 1478f8f45c8617c5d3f46d9ef03754a560517670 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Tue, 25 Jun 2024 13:51:01 +0200 Subject: [PATCH 10/15] Ezra Collective - May the funk be with you --- .../examples}/PRIMEstudy/00- Load.R | 0 .../examples}/PRIMEstudy/01- ImportPRIME.R | 0 .../examples}/PRIMEstudy/02- DescPRIME.R | 0 .../examples}/PRIMEstudy/03- jmPRIME.R | 0 .../examples}/PRIMEstudy/data/PRIMEads.rds | Bin .../examples}/PRIMEstudy/data/adls_pds2019.sas7bdat | Bin .../examples}/PRIMEstudy/data/adsl_pds2019.sas7bdat | Bin .../PRIMEstudy/data/biomark_pds2019.sas7bdat | Bin .../examples/PRIMEstudy/trash}/expon-ph-benchmark.R | 0 .../examples/PRIMEstudy/trash}/expon-ph-outputs.R | 0 .../examples/PRIMEstudy/trash}/trash.R | 0 11 files changed, 0 insertions(+), 0 deletions(-) rename {vignettes => design/examples}/PRIMEstudy/00- Load.R (100%) rename {vignettes => design/examples}/PRIMEstudy/01- ImportPRIME.R (100%) rename {vignettes => design/examples}/PRIMEstudy/02- DescPRIME.R (100%) 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a/vignettes/trash.R b/design/examples/PRIMEstudy/trash/trash.R similarity index 100% rename from vignettes/trash.R rename to design/examples/PRIMEstudy/trash/trash.R From b32aafba011b60f964e3251ec282f3e6bc8158e2 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Wed, 26 Jun 2024 11:38:15 +0200 Subject: [PATCH 11/15] Gil Scott Heron - The get out of the ghetto blues --- design/examples/PRIMEstudy/00- Load.R | 17 ++--- design/examples/PRIMEstudy/01- ImportPRIME.R | 8 +-- design/examples/PRIMEstudy/02- DescPRIME.R | 30 ++++----- design/examples/PRIMEstudy/03- jmPRIME.R | 69 ++++++++++++-------- 4 files changed, 69 insertions(+), 55 deletions(-) diff --git a/design/examples/PRIMEstudy/00- Load.R b/design/examples/PRIMEstudy/00- Load.R index 34f81e099..a20142f4e 100644 --- a/design/examples/PRIMEstudy/00- Load.R +++ b/design/examples/PRIMEstudy/00- Load.R @@ -1,24 +1,25 @@ #' #################################################### -#' +#' #' 2stgTGIOS #' Loading the required R libraries -#' +#' #' Q1-2022 -#' Francois Mercier -#' +#' Francois Mercier +#' #' #################################################### -if (!require("remotes")) { - install.packages("remotes") -} +#' if (!require("remotes")) { +#' install.packages("remotes") +#' } #' remotes::install_github("genentech/jmpost") -#' install.packages("jmpost") +#' install.packages("ghibli") #' General purpose #' ================= library(tidyverse) library(tidyselect) +library(ghibli) #' Data import/export #' ================= diff --git a/design/examples/PRIMEstudy/01- ImportPRIME.R b/design/examples/PRIMEstudy/01- ImportPRIME.R index 5e306819e..44455c0c1 100644 --- a/design/examples/PRIMEstudy/01- ImportPRIME.R +++ b/design/examples/PRIMEstudy/01- ImportPRIME.R @@ -18,10 +18,10 @@ #' UID values #' --------------------------------- -kras<-haven::read_sas("./vignettes/PRIMEstudy/data/biomark_pds2019.sas7bdat") +kras<-haven::read_sas("./design/examples/PRIMEstudy/data/biomark_pds2019.sas7bdat") kras0<-kras |> select("SUBJID", "BMMTR1") -adsl<-haven::read_sas("./vignettes/PRIMEstudy/data/adsl_pds2019.sas7bdat") +adsl<-haven::read_sas("./design/examples/PRIMEstudy/data/adsl_pds2019.sas7bdat") adsl0<-adsl |> select("SUBJID", "ATRT", "DTHDY", "DTH") |> mutate(STUDY="1", DTHYR=DTHDY/365.25) |> @@ -31,7 +31,7 @@ UIDlist<-unique(adsl0$SUBJID) #' length(UIDlist) #' 514 -adtr<-haven::read_sas("./vignettes/PRIMEstudy/data/adls_pds2019.sas7bdat") +adtr<-haven::read_sas("./design/examples/PRIMEstudy/data/adls_pds2019.sas7bdat") keepinadtr0<-c("SUBJID", "VISITDY", "VISIT", "LSSLD") adtr0<-adtr |> @@ -46,7 +46,7 @@ adtr0<-adtr |> #' length(unique(adtr0$SUBJID)) #' 263 -saveRDS(adtr0, file="./vignettes/PRIMEstudy/data/PRIMEads.rds") +saveRDS(adtr0, file="./design/examples/PRIMEstudy/data/PRIMEads.rds") diff --git a/design/examples/PRIMEstudy/02- DescPRIME.R b/design/examples/PRIMEstudy/02- DescPRIME.R index c3cba9d9f..390b75412 100644 --- a/design/examples/PRIMEstudy/02- DescPRIME.R +++ b/design/examples/PRIMEstudy/02- DescPRIME.R @@ -11,7 +11,7 @@ #' sessionInfo() -ads<-readRDS("./vignettes/PRIMEstudy/data/PRIMEads.rds") +ads<-readRDS("./design/examples/PRIMEstudy/data/PRIMEads.rds") #' =============================================== #' Visualize SLD @@ -19,16 +19,18 @@ ads<-readRDS("./vignettes/PRIMEstudy/data/PRIMEads.rds") #' Display SLD spaghetti ybreaks<-c(3, 30, 100, 300) +mycols<-c(rev(ghibli::ghibli_palettes$YesterdayMedium)[c(2,4)]) g0<-ads |> - filter(!is.na(ATRT)) |> - ggplot(aes(x=VISITYR, y=LSSLD))+ - geom_line(aes(group=SUBJID), colour="wheat4", alpha=0.2)+ - geom_point(colour="grey33", alpha=0.3, size=0.9)+ - facet_wrap(~ATRT)+ - scale_x_continuous("Year", breaks=0.5*(0:5))+ - scale_y_continuous("SLD (mm)", breaks=ybreaks)+ - theme_minimal()+ - theme(panel.grid.minor=element_blank()) + filter(!is.na(ATRT)) |> + ggplot(aes(x=VISITYR, y=LSSLD))+ + geom_point(colour="grey33", alpha=0.3, size=0.9)+ + geom_line(aes(group=SUBJID, colour=as.factor(ATRT)), alpha=0.6)+ + facet_wrap(~ATRT)+ + scale_x_continuous("Year", breaks=0.5*(0:5))+ + scale_y_continuous("SLD (mm)", breaks=ybreaks)+ + scale_colour_manual(values=mycols)+ + theme_minimal()+ + theme(panel.grid.minor=element_blank()) g0 #' =============================================== @@ -43,11 +45,9 @@ summary(cox) os.kmest<-survfit(Surv(DTHYR, DTH)~ATRT, data=adsl0) #' Display OS KM g1<-survminer::ggsurvplot(os.kmest, - data=adsl0, - risk.table=T, - break.x.by=.5, legend.title="", - xlab="Year", ylab="Overall survival", - risk.table.fontsize=4, legend=c(0.8, 0.8)) + data=adsl0, risk.table=T, break.x.by=.5, legend.title="", + xlab="Year", ylab="Overall survival", palette = mycols, + risk.table.fontsize=4, legend=c(0.8, 0.8)) g1 diff --git a/design/examples/PRIMEstudy/03- jmPRIME.R b/design/examples/PRIMEstudy/03- jmPRIME.R index a14c9c184..8e2cad20e 100644 --- a/design/examples/PRIMEstudy/03- jmPRIME.R +++ b/design/examples/PRIMEstudy/03- jmPRIME.R @@ -11,7 +11,7 @@ #' sessionInfo() -ads<-readRDS("./vignettes/PRIMEstudy/data/PRIMEads.rds") +ads<-readRDS("./design/examples/PRIMEstudy/data/PRIMEads.rds") #' =============================================== #' Model SLD @@ -24,14 +24,24 @@ tgi.dat<-DataJoint( longi = DataLongitudinal(data=ads, threshold=5, formula= LSSLD~VISITYR) ) -tgi.in<-JointModel(longitudinal=LongitudinalSteinFojo()) - -tgi.samples<-sampleStanModel(tgi.in, data=tgi.dat, iter_warmup=2000, - iter_sampling=1000, chains=2, refresh=500) +tgi.in<-JointModel(longitudinal=LongitudinalSteinFojo( + mu_bsld = prior_lognormal(log(70), .1), + mu_ks = prior_lognormal(log(1.8), .1), + mu_kg = prior_lognormal(log(0.15), .1), + omega_bsld = prior_lognormal(log(0.1), .1), + omega_ks = prior_lognormal(log(0.1), .5), + omega_kg = prior_lognormal(log(0.1), .5), + sigma = prior_lognormal(log(0.18), .5), +)) + +tgi.samples<-sampleStanModel(tgi.in, data=tgi.dat, + iter_sampling = 1000, + iter_warmup = 2000, + chains = 3, parallel_chains = 3) tgi.out<-as.CmdStanMCMC(tgi.samples) print(tgi.out) -#' saveRDS(tgi.out, file="../PRIME/PRIMEtgiout.rds") +#' saveRDS(tgi.out, file="./design/examples/PRIMEstudy/PRIMEtgiout.rds") #' Problems here: #' iPred vs. Obs @@ -52,8 +62,10 @@ surv.dat<-DataJoint( surv.in<-JointModel(survival=SurvivalWeibullPH()) -surv.samples<-sampleStanModel(surv.in, data=surv.dat, iter_warmup=2000, - iter_sampling=1000, chains=2, refresh=500) +surv.samples<-sampleStanModel(surv.in, data=surv.dat, + iter_sampling = 1000, + iter_warmup = 2000, + chains = 3, parallel_chains = 3) surv.out<-as.CmdStanMCMC(surv.samples) print(surv.out) @@ -61,7 +73,14 @@ print(surv.out) expected.surv<-SurvivalQuantities(surv.samples, type="surv", grid=GridGrouped(times=seq(from=0, to=5, by=0.1), groups=split(adsuni$SUBJID, adsuni$ATRT))) -autoplot(expected.surv, add_km=T, add_wrap=F)+theme_minimal() + +mycols<-c(rev(ghibli::ghibli_palettes$YesterdayMedium)[c(2,4)]) +g3<-autoplot(expected.surv, add_km=T, add_wrap=F)+ + scale_fill_manual(values=mycols)+ + scale_colour_manual(values=mycols)+ + theme_minimal()+ + theme(panel.grid.minor=element_blank()) +g3 #' =============================================== @@ -75,35 +94,29 @@ jm.dat<-DataJoint( ) jm.in<-JointModel( - longitudinal=LongitudinalGSF( - mu_bsld = prior_lognormal(log(60), 0.5), - mu_ks = prior_lognormal(log(0.55), 0.5), - mu_kg = prior_lognormal(log(0.15), 0.5), - a_phi = prior_beta(5, 20), - - omega_bsld = prior_lognormal(log(0.1), 0.5), - omega_ks = prior_lognormal(log(0.1), 0.5), - omega_kg = prior_lognormal(log(0.1), 0.5), - b_phi = prior_lognormal(log(0.1), 0.5), - - sigma = prior_lognormal(log(0.18), 0.5) + longitudinal=LongitudinalSteinFojo( + mu_bsld = prior_lognormal(log(70), .1), + mu_ks = prior_lognormal(log(1.8), .1), + mu_kg = prior_lognormal(log(0.15), .1), + omega_bsld = prior_lognormal(log(0.1), .1), + omega_ks = prior_lognormal(log(0.1), .5), + omega_kg = prior_lognormal(log(0.1), .5), + sigma = prior_lognormal(log(0.18), .5), ), survival = SurvivalWeibullPH(), - link = Link(linkIdentity(prior_normal(0.002, 0.2))) + link = Link(linkTTG(prior_normal(0.01, 3))) ) jm.samples<-sampleStanModel(jm.in, data = jm.dat, - iter_sampling = 500, - iter_warmup = 1000, - chains = 1, - parallel_chains = 1 -) + iter_sampling = 1000, + iter_warmup = 2000, + chains = 3, parallel_chains = 3) jm.out<-as.CmdStanMCMC(jm.samples) #' print(jm.out) -#' saveRDS(jm.out, file="../PRIME/PRIMEjm.out.rds") +#' saveRDS(jm.out, file="./design/examples/PRIMEjm.out.rds") expected.surv<-SurvivalQuantities(jm.samples, type="surv", From 58e1e304618d06ff0f589a7d048a08f37d2214e4 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Wed, 26 Jun 2024 15:38:40 +0200 Subject: [PATCH 12/15] Buena Vista Social Club - Candela --- design/examples/{PRIMEstudy => mCRCpub}/00- Load.R | 0 .../{PRIMEstudy => mCRCpub}/01- ImportPRIME.R | 8 ++++---- .../{PRIMEstudy => mCRCpub}/02- DescPRIME.R | 2 +- .../examples/{PRIMEstudy => mCRCpub}/03- jmPRIME.R | 4 ++-- .../{PRIMEstudy => mCRCpub}/data/PRIMEads.rds | Bin .../data/adls_pds2019.sas7bdat | Bin .../data/adsl_pds2019.sas7bdat | Bin .../data/biomark_pds2019.sas7bdat | Bin .../trash/expon-ph-benchmark.R | 0 .../trash/expon-ph-outputs.R | 0 .../examples/{PRIMEstudy => mCRCpub}/trash/trash.R | 0 11 files changed, 7 insertions(+), 7 deletions(-) rename design/examples/{PRIMEstudy => mCRCpub}/00- Load.R (100%) rename design/examples/{PRIMEstudy => mCRCpub}/01- ImportPRIME.R (78%) rename design/examples/{PRIMEstudy => mCRCpub}/02- DescPRIME.R (95%) rename design/examples/{PRIMEstudy => mCRCpub}/03- jmPRIME.R (96%) rename design/examples/{PRIMEstudy => mCRCpub}/data/PRIMEads.rds (100%) rename design/examples/{PRIMEstudy => mCRCpub}/data/adls_pds2019.sas7bdat (100%) rename design/examples/{PRIMEstudy => mCRCpub}/data/adsl_pds2019.sas7bdat (100%) rename design/examples/{PRIMEstudy => mCRCpub}/data/biomark_pds2019.sas7bdat (100%) rename design/examples/{PRIMEstudy => mCRCpub}/trash/expon-ph-benchmark.R (100%) rename design/examples/{PRIMEstudy => mCRCpub}/trash/expon-ph-outputs.R (100%) rename design/examples/{PRIMEstudy => mCRCpub}/trash/trash.R (100%) diff --git a/design/examples/PRIMEstudy/00- Load.R b/design/examples/mCRCpub/00- Load.R similarity index 100% rename from design/examples/PRIMEstudy/00- Load.R rename to design/examples/mCRCpub/00- Load.R diff --git a/design/examples/PRIMEstudy/01- ImportPRIME.R b/design/examples/mCRCpub/01- ImportPRIME.R similarity index 78% rename from design/examples/PRIMEstudy/01- ImportPRIME.R rename to design/examples/mCRCpub/01- ImportPRIME.R index 44455c0c1..fd2e179d9 100644 --- a/design/examples/PRIMEstudy/01- ImportPRIME.R +++ b/design/examples/mCRCpub/01- ImportPRIME.R @@ -18,10 +18,10 @@ #' UID values #' --------------------------------- -kras<-haven::read_sas("./design/examples/PRIMEstudy/data/biomark_pds2019.sas7bdat") +kras<-haven::read_sas("./design/examples/mCRCpub/data/biomark_pds2019.sas7bdat") kras0<-kras |> select("SUBJID", "BMMTR1") -adsl<-haven::read_sas("./design/examples/PRIMEstudy/data/adsl_pds2019.sas7bdat") +adsl<-haven::read_sas("./design/examples/mCRCpub/data/adsl_pds2019.sas7bdat") adsl0<-adsl |> select("SUBJID", "ATRT", "DTHDY", "DTH") |> mutate(STUDY="1", DTHYR=DTHDY/365.25) |> @@ -31,7 +31,7 @@ UIDlist<-unique(adsl0$SUBJID) #' length(UIDlist) #' 514 -adtr<-haven::read_sas("./design/examples/PRIMEstudy/data/adls_pds2019.sas7bdat") +adtr<-haven::read_sas("./design/examples/mCRCpub/data/adls_pds2019.sas7bdat") keepinadtr0<-c("SUBJID", "VISITDY", "VISIT", "LSSLD") adtr0<-adtr |> @@ -46,7 +46,7 @@ adtr0<-adtr |> #' length(unique(adtr0$SUBJID)) #' 263 -saveRDS(adtr0, file="./design/examples/PRIMEstudy/data/PRIMEads.rds") +saveRDS(adtr0, file="./design/examples/mCRCpub/data/PRIMEads.rds") diff --git a/design/examples/PRIMEstudy/02- DescPRIME.R b/design/examples/mCRCpub/02- DescPRIME.R similarity index 95% rename from design/examples/PRIMEstudy/02- DescPRIME.R rename to design/examples/mCRCpub/02- DescPRIME.R index 390b75412..885777b03 100644 --- a/design/examples/PRIMEstudy/02- DescPRIME.R +++ b/design/examples/mCRCpub/02- DescPRIME.R @@ -11,7 +11,7 @@ #' sessionInfo() -ads<-readRDS("./design/examples/PRIMEstudy/data/PRIMEads.rds") +ads<-readRDS("./design/examples/mCRCpub/data/PRIMEads.rds") #' =============================================== #' Visualize SLD diff --git a/design/examples/PRIMEstudy/03- jmPRIME.R b/design/examples/mCRCpub/03- jmPRIME.R similarity index 96% rename from design/examples/PRIMEstudy/03- jmPRIME.R rename to design/examples/mCRCpub/03- jmPRIME.R index 8e2cad20e..242daf3c2 100644 --- a/design/examples/PRIMEstudy/03- jmPRIME.R +++ b/design/examples/mCRCpub/03- jmPRIME.R @@ -11,7 +11,7 @@ #' sessionInfo() -ads<-readRDS("./design/examples/PRIMEstudy/data/PRIMEads.rds") +ads<-readRDS("./design/examples/mCRCpub/data/PRIMEads.rds") #' =============================================== #' Model SLD @@ -41,7 +41,7 @@ tgi.samples<-sampleStanModel(tgi.in, data=tgi.dat, tgi.out<-as.CmdStanMCMC(tgi.samples) print(tgi.out) -#' saveRDS(tgi.out, file="./design/examples/PRIMEstudy/PRIMEtgiout.rds") +#' saveRDS(tgi.out, file="./design/examples/mCRCpub/PRIMEtgiout.rds") #' Problems here: #' iPred vs. Obs diff --git a/design/examples/PRIMEstudy/data/PRIMEads.rds b/design/examples/mCRCpub/data/PRIMEads.rds similarity index 100% rename from design/examples/PRIMEstudy/data/PRIMEads.rds rename to design/examples/mCRCpub/data/PRIMEads.rds diff --git a/design/examples/PRIMEstudy/data/adls_pds2019.sas7bdat b/design/examples/mCRCpub/data/adls_pds2019.sas7bdat similarity index 100% rename from design/examples/PRIMEstudy/data/adls_pds2019.sas7bdat rename to design/examples/mCRCpub/data/adls_pds2019.sas7bdat diff --git a/design/examples/PRIMEstudy/data/adsl_pds2019.sas7bdat b/design/examples/mCRCpub/data/adsl_pds2019.sas7bdat similarity index 100% rename from design/examples/PRIMEstudy/data/adsl_pds2019.sas7bdat rename to design/examples/mCRCpub/data/adsl_pds2019.sas7bdat diff --git a/design/examples/PRIMEstudy/data/biomark_pds2019.sas7bdat b/design/examples/mCRCpub/data/biomark_pds2019.sas7bdat similarity index 100% rename from design/examples/PRIMEstudy/data/biomark_pds2019.sas7bdat rename to design/examples/mCRCpub/data/biomark_pds2019.sas7bdat diff --git a/design/examples/PRIMEstudy/trash/expon-ph-benchmark.R b/design/examples/mCRCpub/trash/expon-ph-benchmark.R similarity index 100% rename from design/examples/PRIMEstudy/trash/expon-ph-benchmark.R rename to design/examples/mCRCpub/trash/expon-ph-benchmark.R diff --git a/design/examples/PRIMEstudy/trash/expon-ph-outputs.R b/design/examples/mCRCpub/trash/expon-ph-outputs.R similarity index 100% rename from design/examples/PRIMEstudy/trash/expon-ph-outputs.R rename to design/examples/mCRCpub/trash/expon-ph-outputs.R diff --git a/design/examples/PRIMEstudy/trash/trash.R b/design/examples/mCRCpub/trash/trash.R similarity index 100% rename from design/examples/PRIMEstudy/trash/trash.R rename to design/examples/mCRCpub/trash/trash.R From c24b4bd3f44dc0e938cdf273c315f3000e7a9a49 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Wed, 26 Jun 2024 16:47:39 +0200 Subject: [PATCH 13/15] Angelique Kidjo - Voodoo child --- design/examples/mCRCpub/03- jmPRIME.R | 4 ---- 1 file changed, 4 deletions(-) diff --git a/design/examples/mCRCpub/03- jmPRIME.R b/design/examples/mCRCpub/03- jmPRIME.R index 242daf3c2..73afdc95f 100644 --- a/design/examples/mCRCpub/03- jmPRIME.R +++ b/design/examples/mCRCpub/03- jmPRIME.R @@ -41,11 +41,7 @@ tgi.samples<-sampleStanModel(tgi.in, data=tgi.dat, tgi.out<-as.CmdStanMCMC(tgi.samples) print(tgi.out) -#' saveRDS(tgi.out, file="./design/examples/mCRCpub/PRIMEtgiout.rds") - #' Problems here: -#' iPred vs. Obs -#' see https://github.com/Genentech/jmpost/blob/fe04d4aa049f5244f7e6e76f97901ef3c7536146/design/examples/quantity_plots.R#L139 longquant_obs<-LongitudinalQuantities(tgi.samples, grid = GridObserved()) From 2d44820045138506af02b02baf82ae913cbf7617 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Thu, 27 Jun 2024 14:14:55 +0200 Subject: [PATCH 14/15] Vampire Weekend - The surfer --- design/examples/mCRCpub/01- ImportHORIZON.R | 76 ++++++++++++ design/examples/mCRCpub/02- DescHORIZON.R | 63 ++++++++++ design/examples/mCRCpub/03- jmHORIZON.R | 109 ++++++++++++++++++ design/examples/mCRCpub/03- jmPRIME.R | 4 +- .../mCRCpub/data/HORIZONIII/HorizOSads.rds | Bin 0 -> 4994 bytes .../mCRCpub/data/HORIZONIII/HorizTGIads.rds | Bin 0 -> 17689 bytes .../mCRCpub/data/HORIZONIII/rdprcist.sas7bdat | Bin 0 -> 3490816 bytes .../mCRCpub/data/HORIZONIII/rdpsubj.sas7bdat | Bin 0 -> 902144 bytes .../mCRCpub/data/{ => PRIME}/PRIMEads.rds | Bin .../data/{ => PRIME}/adls_pds2019.sas7bdat | Bin .../data/{ => PRIME}/adsl_pds2019.sas7bdat | Bin .../data/{ => PRIME}/biomark_pds2019.sas7bdat | Bin 12 files changed, 251 insertions(+), 1 deletion(-) create mode 100644 design/examples/mCRCpub/01- ImportHORIZON.R create mode 100644 design/examples/mCRCpub/02- DescHORIZON.R create mode 100644 design/examples/mCRCpub/03- jmHORIZON.R create mode 100644 design/examples/mCRCpub/data/HORIZONIII/HorizOSads.rds create mode 100644 design/examples/mCRCpub/data/HORIZONIII/HorizTGIads.rds create mode 100644 design/examples/mCRCpub/data/HORIZONIII/rdprcist.sas7bdat create mode 100644 design/examples/mCRCpub/data/HORIZONIII/rdpsubj.sas7bdat rename design/examples/mCRCpub/data/{ => PRIME}/PRIMEads.rds (100%) rename design/examples/mCRCpub/data/{ => PRIME}/adls_pds2019.sas7bdat (100%) rename design/examples/mCRCpub/data/{ => PRIME}/adsl_pds2019.sas7bdat (100%) rename design/examples/mCRCpub/data/{ => PRIME}/biomark_pds2019.sas7bdat (100%) diff --git a/design/examples/mCRCpub/01- ImportHORIZON.R b/design/examples/mCRCpub/01- ImportHORIZON.R new file mode 100644 index 000000000..c6c97145b --- /dev/null +++ b/design/examples/mCRCpub/01- ImportHORIZON.R @@ -0,0 +1,76 @@ +#' #################################################### +#' +#' Data preparation +#' HORIZONIII study (from PDS) +#' +#' Q3-2024 +#' Francois Mercier +#' +#' #################################################### + + +#' sessionInfo() + +#' =============================================== +#' Import and Select +#' =============================================================== + +#' UID values +#' --------------------------------- +subj<-haven::read_sas("data/HORIZONIII/rdpsubj.sas7bdat") +rcist<-haven::read_sas("data/HORIZONIII/rdprcist.sas7bdat") + +#' Only keep patients in PerProtocol set (PP_SET==1) +#' and exposed to BEV for at least 3 weeks (i.e. at least 1st TA visit) +subj0<-subj |> + filter(PP_SET==1, !is.na(BEV_SDY), !is.na(BEV_EDY), BEV_EDY>3*7) |> + mutate(SUBJID=as.character(RANDCODE)) |> + select(SUBJID, LDH1_5) + +#' OS values +#' --------------------------------- +event.df0<-rcist |> + mutate(SUBJID=as.character(RANDCODE)) |> + filter(SUBJID %in% subj0$SUBJID) |> + group_by(SUBJID) %>% slice(1) %>% ungroup() |> + mutate(EVENTYR=OSTIM/365.25, EVENTFL=ifelse(DEATFLAG==1, 0, 1), + ATRT="FOLFOX alone", STUDY="2") |> + select(SUBJID, ATRT, STUDY, EVENTYR, EVENTFL) +#' length(event.df0$SUBJID) +#' 645 + +#' SLD values +#' --------------------------------- +#' - remove rows where SLD is NA +#' - remove rows where patients have PBLCNT=NA i.e. remove patient with at least one post-baseline TA +biom.df0<-rcist |> + mutate(SUBJID=as.character(RANDCODE)) |> + filter(SUBJID %in% subj0$SUBJID) |> + drop_na(STLDI) |> + filter(!is.na(PBLCNT)) |> + mutate(VALUE=ifelse(STLDI==0, 2.5, STLDI*10), STUDY="2", + VISITYR=ORDYTRT/365.25, ATRT="FOLFOX alone") |> + select(SUBJID, STUDY, ATRT, VALUE, VISITYR) +#' length(unique(biom.df0$SUBJID)) +#' 640 + + +retainID<-intersect(unique(biom.df0$SUBJID), event.df0$SUBJID) +#' 640 + +#' =============================================== +#' Build analysis dataset +#' =============================================================== + +subj.df<-subj0 |> filter(SUBJID %in% retainID) + +biom.df<-biom.df0 |> filter(SUBJID %in% retainID) +#' length(unique(biom.df$SUBJID)) + +event.df<-event.df0 |> filter(SUBJID %in% retainID) + +#' saveRDS(event.df, file="data/HORIZONIII/HorizOSads.rds") +#' saveRDS(biom.df, file="data/HORIZONIII/HorizTGIads.rds") + + + diff --git a/design/examples/mCRCpub/02- DescHORIZON.R b/design/examples/mCRCpub/02- DescHORIZON.R new file mode 100644 index 000000000..aec8d9c9a --- /dev/null +++ b/design/examples/mCRCpub/02- DescHORIZON.R @@ -0,0 +1,63 @@ +#' #################################################### +#' +#' Descriptive plots +#' HORIZONIII study (from PDS) +#' +#' Q3-2024 +#' Francois Mercier +#' +#' #################################################### + + +#' sessionInfo() + +#' =============================================== +#' Visualize SLD +#' =============================================== + + +#' Display SLD spaghetti in LDH low/high groups +tk0<-left_join(biom.df, subj.df, by="SUBJID") + +ybreaks<-c(3, 30, 100, 300) +g0<-ggplot(tk0, aes(x=VISITYR, y=VALUE))+ + geom_line(aes(group=SUBJID), colour="grey", alpha=0.2)+ + geom_point(colour="orange4", alpha=0.6, size=0.9)+ + facet_wrap(~as.factor(LDH1_5))+ + scale_x_continuous("Year", breaks=0.5*(0:5))+ + scale_y_continuous("SLD (mm)", breaks=ybreaks)+ + theme_minimal()+ + theme(panel.grid.minor=element_blank()) +g0 + +set.seed(130) +retainIDsub<-sample(retainID, size=60) + +g0sub<-tk0 |> filter(SUBJID %in% retainIDsub) |> + ggplot(aes(x=VISITYR, y=VALUE))+ + geom_line(aes(group=SUBJID), colour="grey", alpha=0.2)+ + geom_point(colour="orange4", alpha=0.6, size=0.9)+ + facet_wrap(~as.factor(SUBJID))+ + scale_x_continuous("Year", breaks=0.5*(0:5))+ + scale_y_continuous("SLD (mm)", breaks=ybreaks)+ + theme_minimal()+ + theme(panel.grid.minor=element_blank()) +g0sub + + +#' =============================================== +#' Visualize OS +#' =============================================== + +#' Display OS KM in all +cox<-coxph(Surv(EVENTYR, EVENTFL)~1, data=event.df) +os.kmest<-survfit(Surv(EVENTYR, EVENTFL)~1, data=event.df) + +g1<-survminer::ggsurvplot(os.kmest, data=event.df, + risk.table=T, break.x.by=0.5, legend.title="", + xlab="Time (year)", ylab="Overall survival", + risk.table.fontsize=4, legend=c(0.8, 0.8)) +g1 + + + diff --git a/design/examples/mCRCpub/03- jmHORIZON.R b/design/examples/mCRCpub/03- jmHORIZON.R new file mode 100644 index 000000000..29de7de43 --- /dev/null +++ b/design/examples/mCRCpub/03- jmHORIZON.R @@ -0,0 +1,109 @@ +#' #################################################### +#' +#' Joint models +#' HORIZONIII study (from PDS) +#' +#' Q3-2024 +#' Francois Mercier +#' +#' #################################################### + + +#' sessionInfo() + +os1<-readRDS("data/HORIZONIII/HorizOSads.rds") +tk1<-readRDS("data/HORIZONIII/HorizTGIads.rds") + +#' =============================================== +#' Model SLD +#' =============================================== + +ads<-biom.df |> filter(SUBJID %in% retainIDsub) +adsuni1<-ads[!duplicated(ads$SUBJID), ] + +tgi.dat<-DataJoint( + subject = DataSubject(data=adsuni1, subject="SUBJID", arm="ATRT", study="STUDY"), + longi = DataLongitudinal(data=ads, threshold=5, formula= VALUE~VISITYR) + ) + +tgi.in<-JointModel(longitudinal=LongitudinalSteinFojo( + mu_bsld=prior_lognormal(log(70), .2), + mu_ks=prior_lognormal(log(0.01), .3), + mu_kg=prior_lognormal(log(0.01), .3), + omega_bsld=prior_lognormal(log(0.5), 0.3), + omega_ks=prior_lognormal(log(0.7), 0.3), + omega_kg=prior_lognormal(log(0.7), 0.3), + sigma=prior_lognormal(log(0.2), 0.1))) + +tgi.samples<-sampleStanModel(tgi.in, data=tgi.dat, iter_warmup=2000, + iter_sampling=1000, chains=3, parallel=3, refresh=500) +tgi.out<-as.CmdStanMCMC(tgi.samples) +print(tgi.out, max_rows=500, digits=5) + +selected_subjects<-sample(adsuni1$SUBJID, 10) +longquant_obs<-LongitudinalQuantities(tgi.samples, grid=GridObserved(subjects=selected_subjects)) +autoplot(longquant_obs) +summary(longquant_obs) + +#' mu_BSLD: hist(rlnorm(1000, log(70), .2)) +#' mu_ks: hist(rlnorm(1000, log(0.01), .3)) +#' om_BSLD: hist(rlnorm(1000, log(0.5), 0.3)) +#' om_ks: hist(rlnorm(1000, log(0.7), 0.3)) +#' om_sigma: hist(rlnorm(1000, log(0.2), 0.1)) + +#' =============================================== +#' Model OS +#' =============================================== + +surv.dat<-DataJoint( + subject = DataSubject(data=os1, subject="SUBJID", arm="ATRT", study="STUDY"), + survival = DataSurvival(data=os1, formula=Surv(EVENTYR, EVENTFL)~1) +) + +surv.in<-JointModel(survival=SurvivalWeibullPH()) + +surv.samples<-sampleStanModel(surv.in, data=surv.dat, iter_warmup=2000, + iter_sampling=1000, chains=3, parallel=3, refresh=500) +surv.out<-as.CmdStanMCMC(surv.samples) +print(surv.out, max_rows=500, digits=5) + +expected.surv<-SurvivalQuantities(surv.samples, type="surv", + grid=GridGrouped(times=seq(from=0, to=3, by=0.1), + groups=split(os1$SUBJID, os1$ATRT))) +autoplot(expected.surv, add_km=T, add_wrap=F)+theme_minimal() + + +#' =============================================== +#' Model JM +#' =============================================== + +jm.dat<-DataJoint( + subject = DataSubject(data=os1, subject="SUBJID", arm="ATRT", study="STUDY"), + longitudinal = DataLongitudinal(data=tk1, threshold=2, formula= VALUE~VISITYR), + survival = DataSurvival(data=os1, formula=Surv(EVENTYR, EVENTFL)~1) +) + +jm.in<-JointModel( + longitudinal=LongitudinalSteinFojo( + mu_bsld=prior_lognormal(log(70), .2), + mu_ks=prior_lognormal(log(0.01), .3), + mu_kg=prior_lognormal(log(0.01), .3), + omega_bsld=prior_lognormal(log(0.5), 0.3), + omega_ks=prior_lognormal(log(0.7), 0.3), + omega_kg=prior_lognormal(log(0.7), 0.3), + sigma=prior_lognormal(log(0.2), 0.1)), + survival=SurvivalWeibullPH(), + link=Link(linkTTG(prior_normal(0.01, 3))) +) + +jm.samples<-sampleStanModel(jm.in, data=jm.dat, + iter_sampling=1000, iter_warmup=2000, chains=3, parallel_chains=3) + +jm.out<-as.CmdStanMCMC(jm.samples) +#' print(jm.out, max_rows=500, digits=5) + +expected.surv<-SurvivalQuantities(jm.samples, type="surv", + grid=GridGrouped(times=seq(from=0, to=3, by=0.1), + groups=split(os1$SUBJID, os1$ATRT))) +autoplot(expected.surv, add_km=T, add_wrap=F)+theme_minimal() + diff --git a/design/examples/mCRCpub/03- jmPRIME.R b/design/examples/mCRCpub/03- jmPRIME.R index 73afdc95f..5b6b9ee16 100644 --- a/design/examples/mCRCpub/03- jmPRIME.R +++ b/design/examples/mCRCpub/03- jmPRIME.R @@ -42,7 +42,9 @@ tgi.out<-as.CmdStanMCMC(tgi.samples) print(tgi.out) #' Problems here: -longquant_obs<-LongitudinalQuantities(tgi.samples, grid = GridObserved()) +selected_subjects<-head(adsuni$SUBJID, 10) +longquant_obs<-LongitudinalQuantities(tgi.samples, grid=GridObserved(subjects=selected_subjects)) +autoplot(longquant_obs) #' =============================================== diff --git a/design/examples/mCRCpub/data/HORIZONIII/HorizOSads.rds b/design/examples/mCRCpub/data/HORIZONIII/HorizOSads.rds new file mode 100644 index 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zTljS1pT#`O^2-QkA5)O;{}-|)Jj?h0=i_HCJ+{B^ZhsU1X4{RQ)n=Kn$kt?=@hso} zuMQZTLgJSp2}cG&zW+bx+4jdUw?_T-&wO9Va_Ebm52!VMX3K<-mVQ#Fq)#fb_HJ#; R*gvDWhBDv(|HbV8|1YJ5^g#ds literal 0 HcmV?d00001 diff --git a/design/examples/mCRCpub/data/PRIMEads.rds b/design/examples/mCRCpub/data/PRIME/PRIMEads.rds similarity index 100% rename from design/examples/mCRCpub/data/PRIMEads.rds rename to design/examples/mCRCpub/data/PRIME/PRIMEads.rds diff --git a/design/examples/mCRCpub/data/adls_pds2019.sas7bdat b/design/examples/mCRCpub/data/PRIME/adls_pds2019.sas7bdat similarity index 100% rename from design/examples/mCRCpub/data/adls_pds2019.sas7bdat rename to design/examples/mCRCpub/data/PRIME/adls_pds2019.sas7bdat diff --git a/design/examples/mCRCpub/data/adsl_pds2019.sas7bdat b/design/examples/mCRCpub/data/PRIME/adsl_pds2019.sas7bdat similarity index 100% rename from design/examples/mCRCpub/data/adsl_pds2019.sas7bdat rename to design/examples/mCRCpub/data/PRIME/adsl_pds2019.sas7bdat diff --git a/design/examples/mCRCpub/data/biomark_pds2019.sas7bdat b/design/examples/mCRCpub/data/PRIME/biomark_pds2019.sas7bdat similarity index 100% rename from design/examples/mCRCpub/data/biomark_pds2019.sas7bdat rename to design/examples/mCRCpub/data/PRIME/biomark_pds2019.sas7bdat From 7c44899038de3e2fa803ac5096ff45a1aa027157 Mon Sep 17 00:00:00 2001 From: mercifr1 Date: Thu, 27 Jun 2024 16:01:48 +0200 Subject: [PATCH 15/15] Sandy Nelson - Let there be drums --- design/examples/mCRCpub/01- ImportHORIZON.R | 95 ++++++++++------- design/examples/mCRCpub/01- ImportPRIME.R | 96 +++++++++++++----- design/examples/mCRCpub/02- DescHORIZON.R | 30 +++--- design/examples/mCRCpub/02- DescPRIME.R | 23 +++-- design/examples/mCRCpub/03- jmHORIZON.R | 80 ++++++++++----- design/examples/mCRCpub/03- jmPRIME.R | 61 ++++++----- .../mCRCpub/data/HORIZONIII/HorizOSads.rds | Bin 4994 -> 4994 bytes .../mCRCpub/data/HORIZONIII/HorizTGIads.rds | Bin 17689 -> 17687 bytes .../mCRCpub/data/PRIME/PRIMEOSads.rds | Bin 0 -> 2994 bytes .../mCRCpub/data/PRIME/PRIMETGIads.rds | Bin 0 -> 9064 bytes .../examples/mCRCpub/data/PRIME/PRIMEads.rds | Bin 16958 -> 0 bytes 11 files changed, 243 insertions(+), 142 deletions(-) create mode 100644 design/examples/mCRCpub/data/PRIME/PRIMEOSads.rds create mode 100644 design/examples/mCRCpub/data/PRIME/PRIMETGIads.rds delete mode 100644 design/examples/mCRCpub/data/PRIME/PRIMEads.rds diff --git a/design/examples/mCRCpub/01- ImportHORIZON.R b/design/examples/mCRCpub/01- ImportHORIZON.R index c6c97145b..0fe7af7f4 100644 --- a/design/examples/mCRCpub/01- ImportHORIZON.R +++ b/design/examples/mCRCpub/01- ImportHORIZON.R @@ -1,76 +1,101 @@ #' #################################################### -#' +#' #' Data preparation #' HORIZONIII study (from PDS) -#' +#' #' Q3-2024 -#' Francois Mercier -#' +#' Francois Mercier +#' #' #################################################### #' sessionInfo() +#' ---------------------------------- +#' Structure analysis data set: +#' ---------------------------------- +#' For time to event sub-model (event.df): +#' *************************** +#' SUBJID (chr) +#' STUDY (chr) +#' ATRT (chr) +#' +#' EVENTYR (num) - Time to event (in years) +#' EVENTFL (0/1) - Flag =1 if the ind died, 0 if censored +#' +#' For longi (TGI) sub-model (biom.df): +#' *************************** +#' SUBJID (chr) +#' STUDY (chr) +#' ATRT (chr) +#' +#' BIOMVAL (num) - Biomarker (here, SLD in mm) value +#' BIOMYR (num) - Biomarker measurement time (in years) +#' ---------------------------------- + + #' =============================================== #' Import and Select #' =============================================================== -#' UID values -#' --------------------------------- -subj<-haven::read_sas("data/HORIZONIII/rdpsubj.sas7bdat") -rcist<-haven::read_sas("data/HORIZONIII/rdprcist.sas7bdat") +#' Event data frame +#' ----------------- +subj<-haven::read_sas("./design/examples/mCRCpub/data/HORIZONIII/rdpsubj.sas7bdat") +rcist<-haven::read_sas("./design/examples/mCRCpub/data/HORIZONIII/rdprcist.sas7bdat") #' Only keep patients in PerProtocol set (PP_SET==1) #' and exposed to BEV for at least 3 weeks (i.e. at least 1st TA visit) -subj0<-subj |> +subj0<-subj |> filter(PP_SET==1, !is.na(BEV_SDY), !is.na(BEV_EDY), BEV_EDY>3*7) |> mutate(SUBJID=as.character(RANDCODE)) |> select(SUBJID, LDH1_5) +#' length(unique(subj0$SUBJID)) +#' 645 -#' OS values -#' --------------------------------- -event.df0<-rcist |> +event.df0<-rcist |> mutate(SUBJID=as.character(RANDCODE)) |> filter(SUBJID %in% subj0$SUBJID) |> group_by(SUBJID) %>% slice(1) %>% ungroup() |> mutate(EVENTYR=OSTIM/365.25, EVENTFL=ifelse(DEATFLAG==1, 0, 1), ATRT="FOLFOX alone", STUDY="2") |> - select(SUBJID, ATRT, STUDY, EVENTYR, EVENTFL) -#' length(event.df0$SUBJID) + select(SUBJID, STUDY, ATRT, EVENTYR, EVENTFL) + +UID.event0<-unique(event.df0$SUBJID) +#' length(UID.event0) #' 645 -#' SLD values -#' --------------------------------- +#' Biomarker (SLD) data frame +#' ----------------- #' - remove rows where SLD is NA #' - remove rows where patients have PBLCNT=NA i.e. remove patient with at least one post-baseline TA -biom.df0<-rcist |> - mutate(SUBJID=as.character(RANDCODE)) |> - filter(SUBJID %in% subj0$SUBJID) |> - drop_na(STLDI) |> - filter(!is.na(PBLCNT)) |> - mutate(VALUE=ifelse(STLDI==0, 2.5, STLDI*10), STUDY="2", - VISITYR=ORDYTRT/365.25, ATRT="FOLFOX alone") |> - select(SUBJID, STUDY, ATRT, VALUE, VISITYR) -#' length(unique(biom.df0$SUBJID)) -#' 640 +biom.df0<-rcist |> + filter(!is.na(PBLCNT), !is.na(STLDI)) |> + mutate(SUBJID=as.character(RANDCODE), STUDY="2", ATRT="FOLFOX alone", + BIOMVAL=ifelse(STLDI==0, 2.5, STLDI*10), + BIOMYR=ORDYTRT/365.25) |> + select(SUBJID, STUDY, ATRT, BIOMVAL, BIOMYR) + +UID.biom0<-unique(biom.df0$SUBJID) +#' length(UID.biom0) +#' 660 +#' Retain matching patients +#' ----------------- -retainID<-intersect(unique(biom.df0$SUBJID), event.df0$SUBJID) +retainID<-intersect(UID.event0, UID.biom0) #' 640 -#' =============================================== -#' Build analysis dataset -#' =============================================================== +event.df<-event.df0 |> filter(SUBJID %in% retainID) +#' length(unique(event.df$SUBJID)) +#' 640 +#' saveRDS(event.df, file="./design/examples/mCRCpub/data/HORIZONIII/HorizOSads.rds") -subj.df<-subj0 |> filter(SUBJID %in% retainID) biom.df<-biom.df0 |> filter(SUBJID %in% retainID) #' length(unique(biom.df$SUBJID)) +#' 640 +#' saveRDS(biom.df, file="./design/examples/mCRCpub/data/HORIZONIII/HorizTGIads.rds") -event.df<-event.df0 |> filter(SUBJID %in% retainID) - -#' saveRDS(event.df, file="data/HORIZONIII/HorizOSads.rds") -#' saveRDS(biom.df, file="data/HORIZONIII/HorizTGIads.rds") diff --git a/design/examples/mCRCpub/01- ImportPRIME.R b/design/examples/mCRCpub/01- ImportPRIME.R index fd2e179d9..74bcb3529 100644 --- a/design/examples/mCRCpub/01- ImportPRIME.R +++ b/design/examples/mCRCpub/01- ImportPRIME.R @@ -11,42 +11,86 @@ #' sessionInfo() +#' ---------------------------------- +#' Structure analysis data set: +#' ---------------------------------- +#' For time to event sub-model (event.df): +#' *************************** +#' SUBJID (chr) +#' STUDY (chr) +#' ATRT (chr) +#' +#' EVENTYR (num) - Time to event (in years) +#' EVENTFL (0/1) - Flag =1 if the ind died, 0 if censored +#' +#' For longi (TGI) sub-model (biom.df): +#' *************************** +#' SUBJID (chr) +#' STUDY (chr) +#' ATRT (chr) +#' +#' BIOMVAL (num) - Biomarker (here, SLD in mm) value +#' BIOMYR (num) - Biomarker measurement time (in years) +#' ---------------------------------- + + #' =============================================== #' Import and Select #' =============================================================== -#' UID values -#' --------------------------------- - -kras<-haven::read_sas("./design/examples/mCRCpub/data/biomark_pds2019.sas7bdat") +#' Event data frame +#' ----------------- +kras<-haven::read_sas("./design/examples/mCRCpub/data/PRIME/biomark_pds2019.sas7bdat") kras0<-kras |> select("SUBJID", "BMMTR1") -adsl<-haven::read_sas("./design/examples/mCRCpub/data/adsl_pds2019.sas7bdat") -adsl0<-adsl |> - select("SUBJID", "ATRT", "DTHDY", "DTH") |> - mutate(STUDY="1", DTHYR=DTHDY/365.25) |> - left_join(kras0, by="SUBJID") |> - filter(BMMTR1=="Wild-type") -UIDlist<-unique(adsl0$SUBJID) -#' length(UIDlist) +adsl<-haven::read_sas("./design/examples/mCRCpub/data/PRIME/adsl_pds2019.sas7bdat") +event.df0<-adsl |> + left_join(kras0, by="SUBJID") |> + filter(BMMTR1=="Wild-type") |> + mutate(STUDY="1", EVENTYR=DTHDY/365.25, EVENTFL=DTH) |> + select("SUBJID", "STUDY", "ATRT", "EVENTYR", "EVENTFL") + +UID.event0<-unique(event.df0$SUBJID) +#' length(UID.event0) #' 514 -adtr<-haven::read_sas("./design/examples/mCRCpub/data/adls_pds2019.sas7bdat") -keepinadtr0<-c("SUBJID", "VISITDY", "VISIT", "LSSLD") - -adtr0<-adtr |> - filter(LSCAT=="Target lesion") |> - select(one_of(keepinadtr0)) |> - mutate(VISITYR=VISITDY/365.25) |> - group_by(SUBJID, VISITDY) |> - slice(1) |> - ungroup() |> - left_join(adsl0, by="SUBJID") |> - filter(!is.na(LSSLD), SUBJID %in% UIDlist) -#' length(unique(adtr0$SUBJID)) + +#' Biomarker (SLD) data frame +#' ----------------- +adtr<-haven::read_sas("./design/examples/mCRCpub/data/PRIME/adls_pds2019.sas7bdat") +biom.df0<-adtr |> + filter(LSCAT=="Target lesion", !is.na(LSSLD)) |> + mutate(STUDY="1", BIOMYR=VISITDY/365.25, BIOMVAL=LSSLD) |> + group_by(SUBJID, VISITDY) |> slice(1) |> ungroup() |> + select("SUBJID", "BIOMYR", "BIOMVAL") + +UID.biom0<-unique(biom.df0$SUBJID) +#' length(UID.biom0) +#' 488 + + +#' Retain matching patients +#' ----------------- +retainID<-intersect(UID.event0, UID.biom0) +#' 263 + +event.df<-event.df0 |> filter(SUBJID %in% retainID) +#' length(unique(event.df$SUBJID)) #' 263 +#' saveRDS(event.df, file="./design/examples/mCRCpub/data/PRIME/PRIMEOSads.rds") + +desn0<-event.df0 |> + filter(SUBJID %in% retainID) |> + select(SUBJID, STUDY, ATRT) + +biom.df<-biom.df0 |> + filter(SUBJID %in% retainID) |> + left_join(desn0, by="SUBJID") +#' length(unique(biom.df$SUBJID)) +#' 263 +#' saveRDS(biom.df, file="./design/examples/mCRCpub/data/PRIME/PRIMETGIads.rds") + -saveRDS(adtr0, file="./design/examples/mCRCpub/data/PRIMEads.rds") diff --git a/design/examples/mCRCpub/02- DescHORIZON.R b/design/examples/mCRCpub/02- DescHORIZON.R index aec8d9c9a..b47624210 100644 --- a/design/examples/mCRCpub/02- DescHORIZON.R +++ b/design/examples/mCRCpub/02- DescHORIZON.R @@ -1,11 +1,11 @@ #' #################################################### -#' +#' #' Descriptive plots #' HORIZONIII study (from PDS) -#' +#' #' Q3-2024 -#' Francois Mercier -#' +#' Francois Mercier +#' #' #################################################### @@ -15,15 +15,13 @@ #' Visualize SLD #' =============================================== - -#' Display SLD spaghetti in LDH low/high groups -tk0<-left_join(biom.df, subj.df, by="SUBJID") +#' biom.df<-readRDS("./design/examples/mCRCpub/data/HORIZONIII/HorizTGIads.rds") +#' summary(biom.df) ybreaks<-c(3, 30, 100, 300) -g0<-ggplot(tk0, aes(x=VISITYR, y=VALUE))+ +g0<-ggplot(biom.df, aes(x=BIOMYR, y=BIOMVAL))+ geom_line(aes(group=SUBJID), colour="grey", alpha=0.2)+ geom_point(colour="orange4", alpha=0.6, size=0.9)+ - facet_wrap(~as.factor(LDH1_5))+ scale_x_continuous("Year", breaks=0.5*(0:5))+ scale_y_continuous("SLD (mm)", breaks=ybreaks)+ theme_minimal()+ @@ -33,8 +31,8 @@ g0 set.seed(130) retainIDsub<-sample(retainID, size=60) -g0sub<-tk0 |> filter(SUBJID %in% retainIDsub) |> - ggplot(aes(x=VISITYR, y=VALUE))+ +g0sub<-biom.df |> filter(SUBJID %in% retainIDsub) |> + ggplot(aes(x=BIOMYR, y=BIOMVAL))+ geom_line(aes(group=SUBJID), colour="grey", alpha=0.2)+ geom_point(colour="orange4", alpha=0.6, size=0.9)+ facet_wrap(~as.factor(SUBJID))+ @@ -49,14 +47,18 @@ g0sub #' Visualize OS #' =============================================== -#' Display OS KM in all +#' event.df<-readRDS("./design/examples/mCRCpub/data/HORIZONIII/HorizOSads.rds") +#' summary(event.df) + cox<-coxph(Surv(EVENTYR, EVENTFL)~1, data=event.df) -os.kmest<-survfit(Surv(EVENTYR, EVENTFL)~1, data=event.df) +summary(cox) +os.kmest<-survfit(Surv(EVENTYR, EVENTFL)~1, data=event.df) +mycols<-c(rev(ghibli::ghibli_palettes$YesterdayMedium)[c(2,4)]) g1<-survminer::ggsurvplot(os.kmest, data=event.df, risk.table=T, break.x.by=0.5, legend.title="", xlab="Time (year)", ylab="Overall survival", - risk.table.fontsize=4, legend=c(0.8, 0.8)) + risk.table.fontsize=4, legend=c(0.8, 0.8), palette = mycols) g1 diff --git a/design/examples/mCRCpub/02- DescPRIME.R b/design/examples/mCRCpub/02- DescPRIME.R index 885777b03..5a371524a 100644 --- a/design/examples/mCRCpub/02- DescPRIME.R +++ b/design/examples/mCRCpub/02- DescPRIME.R @@ -11,24 +11,23 @@ #' sessionInfo() -ads<-readRDS("./design/examples/mCRCpub/data/PRIMEads.rds") - #' =============================================== #' Visualize SLD #' =============================================== +#' biom.df<-readRDS("./design/examples/mCRCpub/data/PRIME/PRIMETGIads.rds") +#' summary(biom.df) + #' Display SLD spaghetti ybreaks<-c(3, 30, 100, 300) mycols<-c(rev(ghibli::ghibli_palettes$YesterdayMedium)[c(2,4)]) -g0<-ads |> - filter(!is.na(ATRT)) |> - ggplot(aes(x=VISITYR, y=LSSLD))+ +g0<-ggplot(data=biom.df, aes(x=BIOMYR, y=BIOMVAL))+ geom_point(colour="grey33", alpha=0.3, size=0.9)+ geom_line(aes(group=SUBJID, colour=as.factor(ATRT)), alpha=0.6)+ facet_wrap(~ATRT)+ scale_x_continuous("Year", breaks=0.5*(0:5))+ scale_y_continuous("SLD (mm)", breaks=ybreaks)+ - scale_colour_manual(values=mycols)+ + scale_colour_manual(values=mycols, guide="none")+ theme_minimal()+ theme(panel.grid.minor=element_blank()) g0 @@ -37,15 +36,17 @@ g0 #' Visualize OS #' =============================================== -osdf<-ads |> - group_by(SUBJID) |> slice(1) |> ungroup() -cox<-coxph(Surv(DTHYR, DTH)~ATRT, data=osdf) +#' event.df<-readRDS("./design/examples/mCRCpub/data/PRIME/PRIMEOSads.rds") +#' summary(event.df) + +cox<-coxph(Surv(EVENTYR, EVENTFL)~ATRT, data=event.df) summary(cox) -os.kmest<-survfit(Surv(DTHYR, DTH)~ATRT, data=adsl0) +os.kmest<-survfit(Surv(EVENTYR, EVENTFL)~ATRT, data=event.df) + #' Display OS KM g1<-survminer::ggsurvplot(os.kmest, - data=adsl0, risk.table=T, break.x.by=.5, legend.title="", + data=event.df, risk.table=T, break.x.by=.5, legend.title="", xlab="Year", ylab="Overall survival", palette = mycols, risk.table.fontsize=4, legend=c(0.8, 0.8)) g1 diff --git a/design/examples/mCRCpub/03- jmHORIZON.R b/design/examples/mCRCpub/03- jmHORIZON.R index 29de7de43..28e789576 100644 --- a/design/examples/mCRCpub/03- jmHORIZON.R +++ b/design/examples/mCRCpub/03- jmHORIZON.R @@ -1,29 +1,40 @@ #' #################################################### -#' +#' #' Joint models #' HORIZONIII study (from PDS) -#' +#' #' Q3-2024 -#' Francois Mercier -#' +#' Francois Mercier +#' #' #################################################### #' sessionInfo() -os1<-readRDS("data/HORIZONIII/HorizOSads.rds") -tk1<-readRDS("data/HORIZONIII/HorizTGIads.rds") + +#' biom.df<-readRDS("./design/examples/mCRCpub/data/PRIME/HorizTGIads.rds") +#' summary(biom.df) + +#' event.df<-readRDS("./design/examples/mCRCpub/data/PRIME/HorizOSads.rds") +#' summary(event.df) + #' =============================================== #' Model SLD #' =============================================== -ads<-biom.df |> filter(SUBJID %in% retainIDsub) -adsuni1<-ads[!duplicated(ads$SUBJID), ] +###### +#' !!!!!!!!!!! +###### +event.subset.for.test<-event.df |> filter(SUBJID %in% retainIDsub) +biom.subset.for.test<-biom.df |> filter(SUBJID %in% retainIDsub) +###### +#' !!!!!!!!!!! +###### tgi.dat<-DataJoint( - subject = DataSubject(data=adsuni1, subject="SUBJID", arm="ATRT", study="STUDY"), - longi = DataLongitudinal(data=ads, threshold=5, formula= VALUE~VISITYR) + subject = DataSubject(data=event.subset.for.test, subject="SUBJID", arm="ATRT", study="STUDY"), + longi = DataLongitudinal(data=biom.subset.for.test, threshold=3, formula= BIOMVAL~BIOMYR) ) tgi.in<-JointModel(longitudinal=LongitudinalSteinFojo( @@ -40,9 +51,13 @@ tgi.samples<-sampleStanModel(tgi.in, data=tgi.dat, iter_warmup=2000, tgi.out<-as.CmdStanMCMC(tgi.samples) print(tgi.out, max_rows=500, digits=5) -selected_subjects<-sample(adsuni1$SUBJID, 10) +#' Display profiles OBS vs IPRED for 10 random individuals +selected_subjects<-sample(event.subset.for.test$SUBJID, 10) longquant_obs<-LongitudinalQuantities(tgi.samples, grid=GridObserved(subjects=selected_subjects)) -autoplot(longquant_obs) +g2<-autoplot(longquant_obs)+ + theme_minimal()+ + theme(panel.grid.minor=element_blank()) +g2 summary(longquant_obs) #' mu_BSLD: hist(rlnorm(1000, log(70), .2)) @@ -51,13 +66,14 @@ summary(longquant_obs) #' om_ks: hist(rlnorm(1000, log(0.7), 0.3)) #' om_sigma: hist(rlnorm(1000, log(0.2), 0.1)) + #' =============================================== #' Model OS #' =============================================== surv.dat<-DataJoint( - subject = DataSubject(data=os1, subject="SUBJID", arm="ATRT", study="STUDY"), - survival = DataSurvival(data=os1, formula=Surv(EVENTYR, EVENTFL)~1) + subject = DataSubject(data=event.df, subject="SUBJID", arm="ATRT", study="STUDY"), + survival = DataSurvival(data=event.df, formula=Surv(EVENTYR, EVENTFL)~1) ) surv.in<-JointModel(survival=SurvivalWeibullPH()) @@ -67,10 +83,18 @@ surv.samples<-sampleStanModel(surv.in, data=surv.dat, iter_warmup=2000, surv.out<-as.CmdStanMCMC(surv.samples) print(surv.out, max_rows=500, digits=5) +#' Display PRED vs OBS surv curves expected.surv<-SurvivalQuantities(surv.samples, type="surv", - grid=GridGrouped(times=seq(from=0, to=3, by=0.1), - groups=split(os1$SUBJID, os1$ATRT))) -autoplot(expected.surv, add_km=T, add_wrap=F)+theme_minimal() + grid=GridGrouped(times=seq(from=0, to=3, by=0.1), + groups=split(event.df$SUBJID, event.df$ATRT))) + +mycols<-c(rev(ghibli::ghibli_palettes$YesterdayMedium)[c(2,4)]) +g3<-autoplot(expected.surv, add_km=T, add_wrap=F)+ + scale_fill_manual(values=mycols)+ + scale_colour_manual(values=mycols)+ + theme_minimal()+ + theme(panel.grid.minor=element_blank()) +g3 #' =============================================== @@ -78,9 +102,9 @@ autoplot(expected.surv, add_km=T, add_wrap=F)+theme_minimal() #' =============================================== jm.dat<-DataJoint( - subject = DataSubject(data=os1, subject="SUBJID", arm="ATRT", study="STUDY"), - longitudinal = DataLongitudinal(data=tk1, threshold=2, formula= VALUE~VISITYR), - survival = DataSurvival(data=os1, formula=Surv(EVENTYR, EVENTFL)~1) + subject = DataSubject(data=event.df, subject="SUBJID", arm="ATRT", study="STUDY"), + longitudinal = DataLongitudinal(data=biom.df, threshold=2, formula= BIOMVAL~BIOMYR), + survival = DataSurvival(data=event.df, formula=Surv(EVENTYR, EVENTFL)~1) ) jm.in<-JointModel( @@ -100,10 +124,16 @@ jm.samples<-sampleStanModel(jm.in, data=jm.dat, iter_sampling=1000, iter_warmup=2000, chains=3, parallel_chains=3) jm.out<-as.CmdStanMCMC(jm.samples) -#' print(jm.out, max_rows=500, digits=5) +print(jm.out, max_rows=500, digits=5) +#' Display PRED vs OBS surv curves expected.surv<-SurvivalQuantities(jm.samples, type="surv", - grid=GridGrouped(times=seq(from=0, to=3, by=0.1), - groups=split(os1$SUBJID, os1$ATRT))) -autoplot(expected.surv, add_km=T, add_wrap=F)+theme_minimal() - + grid=GridGrouped(times=seq(from=0, to=3, by=0.1), + groups=split(event.df$SUBJID, event.df$ATRT))) + +g4<-autoplot(expected.surv, add_km=T, add_wrap=F)+ + scale_fill_manual(values=mycols)+ + scale_colour_manual(values=mycols)+ + theme_minimal()+ + theme(panel.grid.minor=element_blank()) +g4 diff --git a/design/examples/mCRCpub/03- jmPRIME.R b/design/examples/mCRCpub/03- jmPRIME.R index 5b6b9ee16..60e512a64 100644 --- a/design/examples/mCRCpub/03- jmPRIME.R +++ b/design/examples/mCRCpub/03- jmPRIME.R @@ -11,17 +11,21 @@ #' sessionInfo() -ads<-readRDS("./design/examples/mCRCpub/data/PRIMEads.rds") + +#' biom.df<-readRDS("./design/examples/mCRCpub/data/PRIME/PRIMETGIads.rds") +#' summary(biom.df) + +#' event.df<-readRDS("./design/examples/mCRCpub/data/PRIME/PRIMEOSads.rds") +#' summary(event.df) + #' =============================================== #' Model SLD #' =============================================== -adsuni<-ads[!duplicated(ads$SUBJID), ] - tgi.dat<-DataJoint( - subject = DataSubject(data=adsuni, subject="SUBJID", arm="ATRT", study="STUDY"), - longi = DataLongitudinal(data=ads, threshold=5, formula= LSSLD~VISITYR) + subject = DataSubject(data=event.df, subject="SUBJID", arm="ATRT", study="STUDY"), + longi = DataLongitudinal(data=biom.df, threshold=3, formula= BIOMVAL~BIOMYR) ) tgi.in<-JointModel(longitudinal=LongitudinalSteinFojo( @@ -39,10 +43,10 @@ tgi.samples<-sampleStanModel(tgi.in, data=tgi.dat, iter_warmup = 2000, chains = 3, parallel_chains = 3) tgi.out<-as.CmdStanMCMC(tgi.samples) -print(tgi.out) +print(tgi.out, max_rows=500, digits=5) -#' Problems here: -selected_subjects<-head(adsuni$SUBJID, 10) +#' Display profiles OBS vs IPRED for 10 random individuals +selected_subjects<-head(event.df$SUBJID, 10) longquant_obs<-LongitudinalQuantities(tgi.samples, grid=GridObserved(subjects=selected_subjects)) autoplot(longquant_obs) @@ -51,11 +55,9 @@ autoplot(longquant_obs) #' Model OS #' =============================================== -adsuni<-ads[!duplicated(ads$SUBJID), ] - surv.dat<-DataJoint( - subject = DataSubject(data=adsuni, subject="SUBJID", arm="ATRT", study="STUDY"), - survival = DataSurvival(data=adsuni, formula=Surv(DTHYR, DTH)~ATRT) + subject = DataSubject(data=event.df, subject="SUBJID", arm="ATRT", study="STUDY"), + survival = DataSurvival(data=event.df, formula=Surv(EVENTYR, EVENTFL)~ATRT) ) surv.in<-JointModel(survival=SurvivalWeibullPH()) @@ -65,12 +67,12 @@ surv.samples<-sampleStanModel(surv.in, data=surv.dat, iter_warmup = 2000, chains = 3, parallel_chains = 3) surv.out<-as.CmdStanMCMC(surv.samples) -print(surv.out) - +print(surv.out, max_rows=500, digits=5) +#' Display PRED vs OBS surv curves expected.surv<-SurvivalQuantities(surv.samples, type="surv", - grid=GridGrouped(times=seq(from=0, to=5, by=0.1), - groups=split(adsuni$SUBJID, adsuni$ATRT))) + grid=GridGrouped(times=seq(from=0, to=4, by=0.1), + groups=split(event.df$SUBJID, event.df$ATRT))) mycols<-c(rev(ghibli::ghibli_palettes$YesterdayMedium)[c(2,4)]) g3<-autoplot(expected.surv, add_km=T, add_wrap=F)+ @@ -86,9 +88,9 @@ g3 #' =============================================== jm.dat<-DataJoint( - subject = DataSubject(data=adsuni, subject="SUBJID", arm="ATRT", study="STUDY"), - longitudinal = DataLongitudinal(data=ads, threshold=5, formula= LSSLD~VISITYR), - survival = DataSurvival(data=adsuni, formula=Surv(DTHYR, DTH)~ATRT) + subject = DataSubject(data=event.df, subject="SUBJID", arm="ATRT", study="STUDY"), + longitudinal = DataLongitudinal(data=biom.df, threshold=3, formula= BIOMVAL~BIOMYR), + survival = DataSurvival(data=event.df, formula=Surv(EVENTYR, EVENTFL)~ATRT) ) jm.in<-JointModel( @@ -112,18 +114,15 @@ jm.samples<-sampleStanModel(jm.in, chains = 3, parallel_chains = 3) jm.out<-as.CmdStanMCMC(jm.samples) -#' print(jm.out) - -#' saveRDS(jm.out, file="./design/examples/PRIMEjm.out.rds") - +print(jm.out, max_rows=500, digits=5) +#' Display PRED vs OBS surv curves expected.surv<-SurvivalQuantities(jm.samples, type="surv", - grid=GridGrouped(times=seq(from=0, to=5, by=0.1), - groups=split(adsuni$SUBJID, adsuni$ATRT))) -#' Compiling Stan program... -#' Warning: Chain 1 finished unexpectedly! -#' -#' Error: Generating quantities for all MCMC chains failed. 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