diff --git a/DESCRIPTION b/DESCRIPTION index 95fe20b..2ec128d 100644 --- a/DESCRIPTION +++ b/DESCRIPTION @@ -1,7 +1,7 @@ Package: dsSurvival Title: dsSurvival: Privacy preserving survival models for federated individual patient meta-analysis in DataSHIELD Description: DataSHIELD server side base functions for building survival models. -Version: 2.1.0 +Version: 2.0.0 Author: Soumya Banerjee, Demetris Avraam, Xavier Escriba Montagut, Juan Gonzalez, Paul Burton and Tom R P Bishop Maintainer: Soumya Banerjee, Demetris Avraam, Xavier Escriba Montagut, Juan Gonzalez, Paul Burton and Tom R P Bishop License: GPL-3 diff --git a/LICENSE.md b/LICENSE.md new file mode 100644 index 0000000..f288702 --- /dev/null +++ b/LICENSE.md @@ -0,0 +1,674 @@ + GNU GENERAL PUBLIC LICENSE + Version 3, 29 June 2007 + + Copyright (C) 2007 Free Software Foundation, Inc. + Everyone is permitted to copy and distribute verbatim copies + of this license document, but changing it is not allowed. + + Preamble + + The GNU General Public License is a free, copyleft license for +software and other kinds of works. + + The licenses for most software and other practical works are designed +to take away your freedom to share and change the works. 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If your program is a subroutine library, you +may consider it more useful to permit linking proprietary applications with +the library. If this is what you want to do, use the GNU Lesser General +Public License instead of this License. But first, please read +. diff --git a/NAMESPACE b/NAMESPACE index 2055591..2cbd958 100644 --- a/NAMESPACE +++ b/NAMESPACE @@ -9,4 +9,3 @@ export(listDisclosureSettingsDS) export(plotsurvfitDS) export(summarySurvDS) export(survfitDS) -export(vcovDS.coxph) diff --git a/R/vcovDS.coxph.R b/R/vcovDS.coxph.R deleted file mode 100644 index 2ee639b..0000000 --- a/R/vcovDS.coxph.R +++ /dev/null @@ -1,36 +0,0 @@ -#' -#' @title Returns variance-covariance matrix of Cox Proportional Hazard model. -#' @description returns a variance-covariance matrix of Cox Proportional Hazard model from the server side environment. -#' @details Serverside aggregate function {vcovDS.coxph} called by clientside function -#' {ds.vcov.coxph}. -#' returns a list which contains a variance-covariance matrix for a Cox model. -#' This request is not disclosive, because the disclosure checks should be performed in the main function for building -#' the Cox model (e.g. checking for over saturation). -#' For further details see help for the native {vcov} function. -#' @param object name of server-side coxph object. -#' @return a variance-covariance matrix. -#' @author Soumya Banerjee and Tom Bishop (2022). -#' @export -vcovDS.coxph<-function(object=NULL) -{ - - if (is.null(object)) - { - stop("Please provide the name of a survival::coxph object", call.=FALSE) - } - - surv_obj<-eval(parse(text=object), envir = parent.frame()) - - if (class(surv_obj)!="coxph") - { - stop("Object is not of class survival::coxph, please check the name", call.=FALSE) - } - - vcov_res <- stats::vcov(surv_obj) - - return(vcov_res) - - -} -#AGGREGATE FUNCTION -# vcovDS.coxph diff --git a/build_man_test.R b/build_man_test.R new file mode 100644 index 0000000..9be6989 --- /dev/null +++ b/build_man_test.R @@ -0,0 +1,45 @@ +########################################### +# Script to build manuals and test code +# +# Usage: +# R --no-save < build_man_test.R +# +########################################### + +################### +# load libraries +################### +library(devtools) +library(testthat) +library(dsBase) +library(dsBaseClient) +require('DSI') +require('DSOpal') +library(dsSurvival) +library(dsSurvivalClient) + +################## +# build manuals +################## +devtools::build_manual() + +######################## +# update documentation +######################## +devtools::check_man() + +################## +# build vignettes +################## +devtools::build_vignettes() + +################## +# Testing +################## +devtools::test() + +################## +# clean up +################## +gc() + diff --git a/inst/DATASHIELD b/inst/DATASHIELD index 4c05bff..0385e36 100644 --- a/inst/DATASHIELD +++ b/inst/DATASHIELD @@ -3,9 +3,18 @@ AggregateMethods: coxphSummaryDS, cox.zphSLMADS, summarySurvDS, - plotsurvfitDS, - vcovDS.coxph + plotsurvfitDS AssignMethods: coxphSLMAassignDS, SurvDS, survfitDS +Options: + datashield.privacyLevel=5, + default.nfilter.glm=0.33, + default.nfilter.kNN=3, + default.nfilter.string=80, + default.nfilter.subset=3, + default.nfilter.stringShort=20, + default.nfilter.tab=3, + default.nfilter.noise=0.25, + default.nfilter.levels=0.33 diff --git a/man/vcovDS.coxph.Rd b/man/vcovDS.coxph.Rd deleted file mode 100644 index 72d6a3a..0000000 --- a/man/vcovDS.coxph.Rd +++ /dev/null @@ -1,28 +0,0 @@ -% Generated by roxygen2: do not edit by hand -% Please edit documentation in R/vcovDS.coxph.R -\name{vcovDS.coxph} -\alias{vcovDS.coxph} -\title{Returns variance-covariance matrix of Cox Proportional Hazard model.} -\usage{ -vcovDS.coxph(object = NULL) -} -\arguments{ -\item{object}{name of server-side coxph object.} -} -\value{ -a variance-covariance matrix. -} -\description{ -returns a variance-covariance matrix of Cox Proportional Hazard model from the server side environment. -} -\details{ -Serverside aggregate function {vcovDS.coxph} called by clientside function -{ds.vcov.coxph}. -returns a list which contains a variance-covariance matrix for a Cox model. -This request is not disclosive, because the disclosure checks should be performed in the main function for building -the Cox model (e.g. checking for over saturation). -For further details see help for the native {vcov} function. -} -\author{ -Soumya Banerjee and Tom Bishop (2022). -} diff --git a/screenshot_survival_models.png b/screenshot_survival_models.png new file mode 100644 index 0000000..1173542 Binary files /dev/null and b/screenshot_survival_models.png differ diff --git a/vignettes/development_plan.pdf b/vignettes/development_plan.pdf new file mode 100644 index 0000000..6583e24 Binary files /dev/null and b/vignettes/development_plan.pdf differ diff --git a/vignettes/development_plan.rmd b/vignettes/development_plan.rmd new file mode 100644 index 0000000..8f7d571 --- /dev/null +++ b/vignettes/development_plan.rmd @@ -0,0 +1,524 @@ +--- +title: "Meta-analysis of survival models in the DataSHIELD platform" +author: "Soumya Banerjee, Tom Bishop and DataSHIELD technical team " +date: "15 June 2021" +output: + pdf_document: + toc: yes + number_sections: yes + fig_caption: yes + html_document: + toc: yes + df_print: paged +urlcolor: blue +--- + +```{r setup, include=FALSE} +knitr::opts_chunk$set(echo=TRUE) +``` + +# Summary + +This is a document that outlines a vignette for implementing survival models +and meta-analyzing hazard ratios in the DataSHIELD platform. + +# Survival analysis in DataSHIELD + +We outline code for implementing survival models and meta-analysis +of hazard ratios in DataSHIELD. + +All code is available here: + + * https://github.com/neelsoumya/dsSurvival + + * https://github.com/neelsoumya/dsSurvivalClient + + * https://github.com/neelsoumya/dsBase + + * https://github.com/neelsoumya/dsBaseClient + + +# Installation + +Install R Studio and the development environment as described below: + + * https://data2knowledge.atlassian.net/wiki/spaces/DSDEV/pages/12943461/Getting+started + + +Then install the virtual machines as described below: + + * https://data2knowledge.atlassian.net/wiki/spaces/DSDEV/pages/931069953/Installation+Training+Hub-+DataSHIELD+v6 + + +Install the necessary packages by running the following commands in R Studio: + + +``` + +install.packages('devtools') + +library(devtools) + +devtools::install_github('neelsoumya/dsBaseClient') + +devtools::install_github('neelsoumya/dsBase') + +devtools::install_github('neelsoumya/dsSurvivalClient') + +``` + +Install dsBase (neelsoumya/dsBase main branch) and dsSurvival (neelsoumya/dsSurvival main branch) on the Opal virtual machine. + + + +# Computational workflow + +The computational steps are outlined below. +The first step is connecting to the server and loading the survival data. +We assume that the reader is familiar with these details. + +``` + +library(knitr) +library(rmarkdown) +library(tinytex) +library(survival) +library(metafor) +library(ggplot2) +library(survminer) +library(dsSurvivalClient) +require('DSI') +require('DSOpal') +require('dsBaseClient') + +builder <- DSI::newDSLoginBuilder() + +builder$append(server = "study1", + url = "http://192.168.56.100:8080/", + user = "administrator", password = "datashield_test&", + table = "SURVIVAL.EXPAND_NO_MISSING1", driver = "OpalDriver") +builder$append(server = "study2", + url = "http://192.168.56.100:8080/", + user = "administrator", password = "datashield_test&", + table = "SURVIVAL.EXPAND_NO_MISSING2", driver = "OpalDriver") +builder$append(server = "study3", + url = "http://192.168.56.100:8080/", + user = "administrator", password = "datashield_test&", + table = "SURVIVAL.EXPAND_NO_MISSING3", driver = "OpalDriver") + +logindata <- builder$build() + +connections <- DSI::datashield.login(logins = logindata, assign = TRUE, symbol = "D") + + + +``` + + +```{r, include = FALSE} + +#################### +# Load library +#################### +library(knitr) +library(rmarkdown) +library(tinytex) +library(survival) +library(metafor) +library(ggplot2) +library(survminer) +#library(dsSurvival) +library(dsSurvivalClient) +require('DSI') +require('DSOpal') +require('dsBaseClient') + +####################### +# Get data +####################### +builder <- DSI::newDSLoginBuilder() + +builder$append(server = "study1", + url = "http://192.168.56.100:8080/", + user = "administrator", password = "datashield_test&", + table = "SURVIVAL.EXPAND_NO_MISSING1", driver = "OpalDriver") +builder$append(server = "study2", + url = "http://192.168.56.100:8080/", + user = "administrator", password = "datashield_test&", + table = "SURVIVAL.EXPAND_NO_MISSING2", driver = "OpalDriver") +builder$append(server = "study3", + url = "http://192.168.56.100:8080/", + user = "administrator", password = "datashield_test&", + table = "SURVIVAL.EXPAND_NO_MISSING3", driver = "OpalDriver") + +logindata <- builder$build() + +############## +# login +############## + +# Log onto the remote Opal training servers +connections <- DSI::datashield.login(logins = logindata, assign = TRUE, symbol = "D") + +``` + +# Creating server-side variables for survival analysis + +We now outline some steps for analysing survival data. + +* make sure that the outcome variable is numeric + +``` +ds.asNumeric(x.name = "D$cens", + newobj = "EVENT", + datasources = connections) + +ds.asNumeric(x.name = "D$survtime", + newobj = "SURVTIME", + datasources = connections) +``` + +* convert time id variable to a factor + +``` + +ds.asFactor(input.var.name = "D$time.id", + newobj = "TID", + datasources = connections) + +``` + +* create in the server-side the log(survtime) variable + +``` + +ds.log(x = "D$survtime", + newobj = "log.surv", + datasources = connections) + +``` + +* create start time variable + +``` + +ds.asNumeric(x.name = "D$starttime", + newobj = "STARTTIME", + datasources = connections) + +ds.asNumeric(x.name = "D$endtime", + newobj = "ENDTIME", + datasources = connections) + +``` + + + +```{r, include=FALSE} + +# make sure that the outcome is numeric +ds.asNumeric(x.name = "D$cens", + newobj = "EVENT", + datasources = connections) + +ds.asNumeric(x.name = "D$survtime", + newobj = "SURVTIME", + datasources = connections) + +# convert time id variable to a factor +ds.asFactor(input.var.name = "D$time.id", + newobj = "TID", + datasources = connections) + +# create in the server-side the log(survtime) variable +ds.log(x = "D$survtime", + newobj = "log.surv", + datasources = connections) + +# create start time variable +ds.asNumeric(x.name = "D$starttime", + newobj = "STARTTIME", + datasources = connections) + +# create end time variable +ds.asNumeric(x.name = "D$endtime", + newobj = "ENDTIME", + datasources = connections) + + +# check which variables exist +dsBaseClient::ds.ls() + +# call new function modify NAMESPACE and DESCRIPTION +# call coxph server side +# client side function is here: +# https://github.com/neelsoumya/dsBaseClient/blob/absolute_newbie_client/R/ds.coxph.SLMA.R +# server side function is here: +# https://github.com/neelsoumya/dsBase/blob/absolute_newbie/R/coxphSLMADS.R +``` + + +# Create survival object and call ds.coxph.SLMA() + + +* use constructed Surv object in *ds.coxph.SLMA()* + +``` +dsSurvivalClient::ds.Surv(time='STARTTIME', time2='ENDTIME', + event = 'EVENT', objectname='surv_object', + type='counting') + +coxph_model_full <- dsSurvivalClient::ds.coxph.SLMA(formula = 'surv_object~D$age+D$female') + +``` + +* use direct inline call to *survival::Surv()* + +``` + +dsSurvivalClient::ds.coxph.SLMA(formula = 'survival::Surv(time=SURVTIME,event=EVENT)~D$age+D$female', + dataName = 'D', + datasources = connections) + +``` + +* call with *survival::strata()* + +``` + +coxph_model_strata <- dsSurvivalClient::ds.coxph.SLMA(formula = 'surv_object~D$age + + survival::strata(D$female)') + +summary(coxph_model_strata) + +``` + + +```{r, include=FALSE} + +# 1. use constructed surv object in coxph +dsSurvivalClient::ds.Surv(time='STARTTIME', time2='ENDTIME', event = 'EVENT', objectname='surv_object', type='counting') +coxph_model_full <- dsSurvivalClient::ds.coxph.SLMA(formula = 'surv_object~D$age+D$female') + +# 2. use direct inline call +dsSurvivalClient::ds.coxph.SLMA(formula = 'survival::Surv(time=SURVTIME,event=EVENT)~D$age+D$female', dataName = 'D', datasources = connections) + +# 3. Call with strata() +coxph_model_strata <- dsSurvivalClient::ds.coxph.SLMA(formula = 'surv_object~D$age+survival::strata(D$female)') +summary(coxph_model_strata) + +``` + +# Summary of survival objects + +We can also summarize a server-side object of type *survival::Surv()* +using a call to *ds.coxphSummary()*. This will provide a non-disclosive +summary of the server-side object. An example call is shown below: + + +``` + +dsSurvivalClient::ds.coxphSummary(x = 'coxph_serverside') + +``` + + + +```{r, include=FALSE} + +################################# +# summary of coxphSLMA +################################# +# TODO: +# dsBaseClient::ds.summary(x = 'surv_object') +# dsBaseClient::ds.class(x = 'surv_object') +# dsBaseClient::ds.mean(x='surv_object') + + +################################# +# TODO: Plot survival curves +################################# +# fit <- survival::survfit(formula = 'surv_object~D$age+D$female', data = 'D') +# need ds.survfit() and survfitDS() +# fit_model <- ds.survfit(coxph_model[1]) +# plot(fit_model) + +# TODO: +# plot(survfit_km, fun="cloglog") + +# TODO: +# ggplot like functionality see other functions + +# In dsBaseClient:: +# ds.survfit() +# datashield.aggregate("survfitDS", ....) +# return (the fit model) + +# In dsBase:: +# survfitDS(coxph_model) +# fit_model <- survival::survfit(coxph_model, newdata = 'D') +# return (fit_model) + +# TODO: dsSurvivalClient::ds.survfit(formula='surv_object~1', objectname='survfit_object') +# verify that object has been created +dsBaseClient::ds.ls() + +# ERROR summary of survfit not allowed +# dsBaseClient::ds.summary(x='survfit_object') +# dsBaseClient::ds.mean(x='survfit_object') + +``` + + +# Diagnostics for Cox proportional hazards models + +We have also created functions to test for the assumptions of +Cox proportional hazards models. + +``` +dsSurvivalClient::ds.coxphSLMAassign(formula = 'surv_object~D$age+D$female', + objectname = 'coxph_serverside') + +dsSurvivalClient::ds.cox.zphSLMA(fit = 'coxph_serverside') + +dsSurvivalClient::ds.coxphSummary(x = 'coxph_serverside') + +``` + +A diagnostic summary is shown below. + +```{r, echo=FALSE} + +dsSurvivalClient::ds.coxphSLMAassign(formula = 'surv_object~D$age+D$female', objectname = 'coxph_serverside') + +dsSurvivalClient::ds.cox.zphSLMA(fit = 'coxph_serverside') + +dsSurvivalClient::ds.coxphSummary(x = 'coxph_serverside') + +``` + + + +# Meta-analyze hazard ratios + +We now outline how the hazard ratios from the survival models are meta-analyzed. +We use the *metafor* package for meta-analysis. We show the summary of an +example meta-analysis and a forest plot below. The forest plot shows a basic +example of meta-analyzed hazard ratios from a survival model (analyzed in +dsSurvivalClient). + +The log-hazard ratios and their standard errors from each study can be +found after running *ds.coxphSLMA()* + +The hazard ratios can then be meta-analyzed: + +``` + +input_logHR = c(coxph_model_full$study1$coefficients[1,2], + coxph_model_full$study2$coefficients[1,2], + coxph_model_full$study3$coefficients[1,2]) + +input_se = c(coxph_model_full$study1$coefficients[1,3], + coxph_model_full$study2$coefficients[1,3], + coxph_model_full$study3$coefficients[1,3]) + +metafor::rma(log_hazard_ratio, sei = se_hazard_ratio, method = 'REML') + +``` + +A summary of this meta-analyzed model is shown below. + + +```{r, echo=FALSE} + +# TODO: for each study +for (i_temp_counter in c(1:length(coxph_model_full))) +{ + +} + +# list of hazard ratios for first parameter (age) over 3 studies +input_logHR = c(coxph_model_full$study1$coefficients[1,2], coxph_model_full$study2$coefficients[1,2], coxph_model_full$study3$coefficients[1,2]) +input_se = c(coxph_model_full$study1$coefficients[1,3], coxph_model_full$study2$coefficients[1,3], coxph_model_full$study3$coefficients[1,3]) + +meta_model <- metafor::rma(input_logHR, sei = input_se, method = 'REML') +summary(meta_model) + +####################################################### +# forest plots of final meta-analyzed hazard ratios +####################################################### +``` + +We now show a forest plot with the meta-analyzed hazard ratios. The hazard ratios come +from the dsSurvivalClient function *ds.coxphSLMA()*. The hazard ratios are meta-analyzed +using the *metafor* package. + +```{r fig.cap="Example forest plot of meta-analyzed hazard ratios.", echo=FALSE} + +metafor::forest.rma(x = meta_model) + +``` + +# Plotting of privacy-preserving survival curves + +We also plot privacy preserving survival curves. Please note that is work in progress and is only available on a separate development branch. There will be a full release in v1.1.0. + +``` +dsSurvivalClient::ds.survfit(formula='surv_object~1', objectname='survfit_object') + +dsSurvivalClient::ds.plotsurvfit(formula = 'survfit_object') + +``` + + +```{r, echo = FALSE} + + +dsSurvivalClient::ds.survfit(formula='surv_object~1', objectname='survfit_object') + + +``` + +```{r fig.cap="Privacy preserving survival curves.", echo = FALSE} + +dsSurvivalClient::ds.plotsurvfit(formula = 'survfit_object') + +# dsSurvivalClient::ds.plotsurvfit(formula = 'survfit_object', method_anonymization = 1, knn = 20) + +``` + +\newpage + +```{r, include=FALSE} + +############################################# +# disconnect +############################################# +DSI::datashield.logout(conns = connections) + +``` + + +# Acknowledgements + +We acknowledge the help and support of the DataSHIELD technical team. +We are especially grateful to Yannick Marcon, Paul Burton, Demetris Avraam, Stuart Wheater, Patricia Ryser-Welch, Xavier Escriba, Juan Gonzalez and Wolfgang Vichtbauer for fruitful discussions and feedback. + + +# References + + * https://github.com/datashield + + * http://www.metafor-project.org + + * https://github.com/neelsoumya/dsBase + + * https://github.com/neelsoumya/dsBaseClient + + * https://github.com/neelsoumya/dsSurvival + + * https://github.com/neelsoumya/dsSurvivalClient + + * https://github.com/neelsoumya/datashield_testing_basic + +