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README.md

simjm

CRAN_Status_Badge License

simjm is an R package that allows the user to simulate data from a shared parameter joint model for longitudinal and time-to-event data.

The shared parameter joint model from which the simulated data is generated is based on the model formulation described for the stan_jm modelling function in the rstanarm R package. See this vignette for some of the details. The shared parameter joint model can be univariate (one longitudinal marker) or multivariate (more than one longitudinal marker).

For the longitudinal submodel a generalised linear mixed model is assumed with any of the family choices allowed by stats::glm. If a multivariate joint model is specified, then the longitudinal submodel consists of a multivariate generalized linear model (GLM) with group-specific terms (at the individual-level) that are assumed to be correlated across the different GLM submodels. It is possible to specify a different outcome type (for example a different family and/or link function) for each of the GLM submodels, by providing a list of family objects in the family argument to the simjm call. Auxiliary parameters for each of the families can be specified via the betaLong_aux arugment to the simjm call. For each longitudinal marker submodel, the population-level longitudinal trajectory is determined via the fixed_trajectory argument. This can be specified as either "none" (intercept only), "linear" (intercept and linear slope), "quadratic" (intercept, linear slope, and quadratic term), or "cubic" (the default, intercept, linear slope, quadratic term, and cubic term). In addition, the subject-specific deviations from this trajectory (i.e. subject-specific parameters, also known as subject-level random effects) are determined via the random_trajectory argument (specified in a similar manner to the fixed_trajectory argument).

Simulated event times are generated via a call to the simsurv package, which uses the approach described in Crowther and Lambert (2013) whereby the cumulative hazard is evaluated using numerical quadrature and survival times are generated using an iterative algorithm which nests the quadrature-based evaluation of the cumulative hazard inside Brent's (1973) univariate root finder. A variety of association structures can be specified for the joint model, however, the user is currently only allowed to choose one type of association structure for a given simulated dataset (i.e. only one association structure can be specified, but there are a variety of choices). Currently the only baseline hazard available for the event submodel is a Weibull distribution, but the "true" shape parameter can be specified by the user via the betaEvent_aux argument to the simjm call.

Note: This package was developed as an extension of the simjm function in the survtd package written by Margarita Moreno-Betancur, and described here. The survtd package handles time-varying covariates in time-to-event models via a two-stage multiple imputation joint modelling approach. In comparison, the simjm package described here focuses on a variety of association structures for linking the longitudinal and event submodels, and a variety of family distributions for the longitudinal outcomes.

Note: Please note that the version available on GitHub is the most up-to-date development version of the package. A stable version of the package will be available from CRAN once it is released.

Getting Started

Prerequisites

The simjm package includes the simsurv package as a dependency. The simsurv package can be downloaded from here.

Installation

You can install simjm directly from GitHub using the devtools package. To do this you should first check you have devtools installed by executing the following commands from within your R session:

if (!require(devtools)) {
  install.packages("devtools")
}

Then execute the following commands to install simjm:

library(devtools)
install_github("sambrilleman/simjm")

Example

Here we show some basic calls to simjm to simulate various types of datasets.

Note that by default simjm will simulate data for three longitudinal biomarkers. However, if we only want one or two longitudinal biomarkers then we simply need to adjust the "true" parameters accordingly so that we still get realistic survival times. Some examples of appropriate "true" parameter values are given below.

# For one longitudinal marker:
simdat1 <- simjm(M = 1, betaEvent_assoc = 0.03)

# For two longitudinal markers:
simdat2 <- simjm(M = 2, betaEvent_assoc = 0.015)

# For three longitudinal markers, we can just use the defaults:
simdat3 <- simjm()

# Simulate three longitudinal markers, using "etaslope"
# association structure
simdat4 <- simjm(assoc = "etaslope", betaEvent_assoc = 0.3)

And here is an example of the resulting data frames:

simdat2$Event %>% dplyr::filter(id %in% 1:2)
#>   id Z1         Z2 eventtime status
#> 1  1  0 -1.6072995  20.00000      0
#> 2  2  0 -0.7013221  12.51011      1
simdat2$Long1 %>% dplyr::filter(id %in% 1:2)
#>    id Z1         Z2 eventtime status        tij    Yij_1
#> 1   1  0 -1.6072995  20.00000      0  0.0000000 7.407485
#> 2   1  0 -1.6072995  20.00000      0  7.8174792 8.248891
#> 3   1  0 -1.6072995  20.00000      0  9.0557943 7.174677
#> 4   1  0 -1.6072995  20.00000      0  9.3296569 7.241487
#> 5   1  0 -1.6072995  20.00000      0  9.4837721 8.056077
#> 6   1  0 -1.6072995  20.00000      0 14.5213306 7.084750
#> 7   1  0 -1.6072995  20.00000      0 17.8353023 5.609793
#> 8   1  0 -1.6072995  20.00000      0 18.2803002 6.196316
#> 9   1  0 -1.6072995  20.00000      0 19.3026583 5.134052
#> 10  1  0 -1.6072995  20.00000      0 19.7686089 5.413853
#> 11  2  0 -0.7013221  12.51011      1  0.0000000 7.930274
#> 12  2  0 -0.7013221  12.51011      1  0.9755494 7.564502
#> 13  2  0 -0.7013221  12.51011      1  2.7564974 8.828539
#> 14  2  0 -0.7013221  12.51011      1  2.9984159 7.187226
#> 15  2  0 -0.7013221  12.51011      1  5.2723265 7.329603
#> 16  2  0 -0.7013221  12.51011      1  7.1082889 7.550815
#> 17  2  0 -0.7013221  12.51011      1 10.9639076 7.311300
simdat2$Long2 %>% dplyr::filter(id %in% 1:2)
#>    id Z1         Z2 eventtime status         tij     Yij_2
#> 1   1  0 -1.6072995  20.00000      0  0.00000000  8.946639
#> 2   1  0 -1.6072995  20.00000      0  0.06402065  8.782643
#> 3   1  0 -1.6072995  20.00000      0  0.06828614 10.131194
#> 4   1  0 -1.6072995  20.00000      0  1.00358446  8.953131
#> 5   1  0 -1.6072995  20.00000      0  2.85765766  9.108531
#> 6   1  0 -1.6072995  20.00000      0  7.85927276  7.711013
#> 7   1  0 -1.6072995  20.00000      0 11.98695763  7.932241
#> 8   1  0 -1.6072995  20.00000      0 14.67148988  8.327863
#> 9   1  0 -1.6072995  20.00000      0 19.34600598  6.102380
#> 10  1  0 -1.6072995  20.00000      0 19.60524346  5.205007
#> 11  2  0 -0.7013221  12.51011      1  0.00000000 10.182755
#> 12  2  0 -0.7013221  12.51011      1  2.88195474  9.638174
#> 13  2  0 -0.7013221  12.51011      1  4.60165111  9.835940
#> 14  2  0 -0.7013221  12.51011      1 12.02851147  8.827208

Bug Reports

If you find any bugs, please file an issue or report them via email to Sam Brilleman.

References

  1. Crowther MJ, and Lambert PC. Simulating biologically plausible complex survival data. Statistics in Medicine 2013; 32, 4118--4134. doi:10.1002/sim.5823

  2. Bender R, Augustin T, and Blettner M. Generating survival times to simulate Cox proportional hazards models. Statistics in Medicine 2005; 24(11), 1713--1723.

  3. Brent R. (1973) Algorithms for Minimization without Derivatives. Englewood Cliffs, NJ: Prentice-Hall.

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