Package 'msm'

Title: Multi-State Markov and Hidden Markov Models in Continuous Time
Description: Functions for fitting continuous-time Markov and hidden Markov multi-state models to longitudinal data. Designed for processes observed at arbitrary times in continuous time (panel data) but some other observation schemes are supported. Both Markov transition rates and the hidden Markov output process can be modelled in terms of covariates, which may be constant or piecewise-constant in time.
Authors: Christopher Jackson [aut, cre]
Maintainer: Christopher Jackson <[email protected]>
License: GPL (>= 2)
Version: 1.8.2
Built: 2024-12-08 07:20:53 UTC
Source: CRAN

Help Index


Multi-State Markov and Hidden Markov Models in Continuous Time

Description

msm: Functions for fitting continuous-time Markov and hidden Markov multi-state models to longitudinal data. Designed for processes observed at arbitrary times in continuous time (intermittently observed or panel data) but some other observation schemes are supported. Both Markov transition rates and the hidden Markov output process can be modelled in terms of covariates, which may be constant or piecewise-constant in time.

Author(s)

Maintainer: Christopher Jackson [email protected]

See Also

Useful links:


Aortic aneurysm progression data

Description

This dataset contains longitudinal measurements of grades of aortic aneurysms, measured by ultrasound examination of the diameter of the aorta.

Format

A data frame containing 4337 rows, with each row corresponding to an ultrasound scan from one of 838 men over 65 years of age.

ptnum (numeric) Patient identification number
age (numeric) Recipient age at examination (years)
diam (numeric) Aortic diameter
state (numeric) State of aneurysm.

The states represent successive degrees of aneurysm severity, as indicated by the aortic diameter.

State 1 Aneurysm-free < 30 cm
State 2 Mild aneurysm 30-44 cm
State 3 Moderate aneurysm 45-54 cm
State 4 Severe aneurysm > 55 cm

683 of these men were aneurysm-free at age 65 and were re-screened every two years. The remaining men were aneurysmal at entry and had successive screens with frequency depending on the state of the aneurysm. Severe aneurysms are repaired by surgery.

Source

The Chichester, U.K. randomised controlled trial of screening for abdominal aortic aneurysms by ultrasonography.

References

Jackson, C.H., Sharples, L.D., Thompson, S.G. and Duffy, S.W. and Couto, E. Multi-state Markov models for disease progression with classification error. The Statistician, 52(2): 193–209 (2003)

Couto, E. and Duffy, S. W. and Ashton, H. A. and Walker, N. M. and Myles, J. P. and Scott, R. A. P. and Thompson, S. G. (2002) Probabilities of progression of aortic aneurysms: estimates and implications for screening policy Journal of Medical Screening 9(1):40–42


Bootstrap resampling for multi-state models

Description

Draw a number of bootstrap resamples, refit a msm model to the resamples, and calculate statistics on the refitted models.

Usage

boot.msm(
  x,
  stat = pmatrix.msm,
  B = 1000,
  file = NULL,
  cores = NULL,
  remove.errors = TRUE
)

Arguments

x

A fitted msm model, as output by msm.

stat

A function to call on each refitted msm model. By default this is pmatrix.msm, returning the transition probability matrix in one time unit. If NULL then no function is computed.

B

Number of bootstrap resamples.

file

Name of a file in which to save partial results after each replicate. This is saved using save and can be restored using load, producing an object called boot.list containing the partial results. Not supported when using parallel processing.

cores

Number of processor cores to use for parallel processing. Requires the doParallel package to be installed. If not specified, parallel processing is not used. If cores is set to the string "default", the default methods of makeCluster (on Windows) or registerDoParallel (on Unix-like) are used.

remove.errors

If TRUE then bootstrap refits which resulted in an error are removed from the returned list, and a message is returned which states the proportion of failed fits and the first error message. If FALSE, then the error message for failed refits is placed in the corresponding component of the returned list.

Details

The bootstrap datasets are computed by resampling independent pairs of observations at successive times (for non-hidden models without censoring), or independent individual series (for hidden models or models with censoring). Therefore this approach doesn't work if, for example, the data for a HMM consist of a series of observations from just one individual, and is inaccurate for small numbers of independent transitions or individuals.

Confidence intervals or standard errors for the corresponding statistic can be calculated by summarising the returned list of B replicated outputs. This is currently implemented for most the output functions qmatrix.msm, ematrix.msm, qratio.msm, pmatrix.msm, pmatrix.piecewise.msm, totlos.msm and prevalence.msm. For other outputs, users will have to write their own code to summarise the output of boot.msm.

Most of msm's output functions present confidence intervals based on asymptotic standard errors calculated from the Hessian. These are expected to be underestimates of the true standard errors (Cramer-Rao lower bound). Some of these functions use a further approximation, the delta method (see deltamethod) to obtain standard errors of transformed parameters. Bootstrapping should give a more accurate estimate of the uncertainty.

An alternative method which is less accurate though faster than bootstrapping, but more accurate than the delta method, is to draw a sample from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix), and summarise the transformed estimates. See pmatrix.msm.

All objects used in the original call to msm which produced x, such as the qmatrix, should be in the working environment, or else boot.msm will produce an “object not found” error. This enables boot.msm to refit the original model to the replicate datasets. However there is currently a limitation. In the original call to msm, the "formula" argument should be specified directly, as, for example,

msm(state ~ time, data = ...)

and not, for example,

form = data$state ~ data$time

msm(formula=form, data = ...)

otherwise boot.msm will be unable to draw the replicate datasets.

boot.msm will also fail with an incomprehensible error if the original call to msm used a used-defined object whose name is the same as a built-in R object, or an object in any other loaded package. For example, if you have called a Q matrix q, when q() is the built-in function for quitting R.

If stat is NULL, then B different msm model objects will be stored in memory. This is unadvisable, as msm objects tend to be large, since they contain the original data used for the msm fit, so this will be wasteful of memory.

To specify more than one statistic, write a function consisting of a list of different function calls, for example,

stat = function(x) list (pmatrix.msm(x, t=1), pmatrix.msm(x, t=2))

Value

A list with B components, containing the result of calling function stat on each of the refitted models. If stat is NULL, then each component just contains the refitted model. If one of the B model fits was unsuccessful and resulted in an error, then the corresponding list component will contain the error message.

Author(s)

C.H.Jackson <[email protected]>

References

Efron, B. and Tibshirani, R.J. (1993) An Introduction to the Bootstrap, Chapman and Hall.

See Also

qmatrix.msm, qratio.msm, sojourn.msm, ematrix.msm, pmatrix.msm, pmatrix.piecewise.msm, totlos.msm, prevalence.msm.

Examples

## Not run: 
  ## Psoriatic arthritis example
  data(psor)
  psor.q <- rbind(c(0,0.1,0,0),c(0,0,0.1,0),c(0,0,0,0.1),c(0,0,0,0))
  psor.msm <- msm(state ~ months, subject=ptnum, data=psor, qmatrix =
    psor.q, covariates = ~ollwsdrt+hieffusn,
    constraint = list(hieffusn=c(1,1,1),ollwsdrt=c(1,1,2)),
    control = list(REPORT=1,trace=2), method="BFGS")
  ## Bootstrap the baseline transition intensity matrix.  This will take a long time.
  q.list <- boot.msm(psor.msm, function(x)x$Qmatrices$baseline)
  ## Manipulate the resulting list of matrices to calculate bootstrap standard errors.
  apply(array(unlist(q.list), dim=c(4,4,5)), c(1,2), sd)
  ## Similarly calculate a bootstrap 95% confidence interval
  apply(array(unlist(q.list), dim=c(4,4,5)), c(1,2),
        function(x)quantile(x, c(0.025, 0.975)))
  ## Bootstrap standard errors are larger than the asymptotic standard
  ## errors calculated from the Hessian
  psor.msm$QmatricesSE$baseline

## End(Not run)

Bronchiolitis obliterans syndrome after lung transplants

Description

A dataset containing histories of bronchiolitis obliterans syndrome (BOS) from lung transplant recipients. BOS is a chronic decline in lung function, often observed after lung transplantation. The condition is classified into four stages of severity: none, mild, moderate and severe.

Format

A data frame containing 638 rows, grouped by patient, including histories of 204 patients. The first observation for each patient is defined to be stage 1, no BOS, at six months after transplant. Subsequent observations denote the entry times into stages 2, 3, 4, representing mild, moderate and severe BOS respectively, and stage 5, representing death.

ptnum (numeric) Patient identification number
time (numeric) Months after transplant
state (numeric) BOS state entered at this time

Details

The entry time of each patient into each stage of BOS was estimated by clinicians, based on their history of lung function measurements and acute rejection and infection episodes. BOS is only assumed to occur beyond six months after transplant. In the first six months the function of each patient's new lung stabilises. Subsequently BOS is diagnosed by comparing the lung function against the "baseline" value.

The objects bos3 and bos4 contain the same data, but with mild/moderate/severe combined, and moderate/severe combined, to give 3 and 4-state representations respectively.

Source

Papworth Hospital, U.K.

References

Heng. D. et al. (1998). Bronchiolitis Obliterans Syndrome: Incidence, Natural History, Prognosis, and Risk Factors. Journal of Heart and Lung Transplantation 17(12)1255–1263.


Heart transplant monitoring data

Description

A series of approximately yearly angiographic examinations of heart transplant recipients. The state at each time is a grade of cardiac allograft vasculopathy (CAV), a deterioration of the arterial walls.

Format

A data frame containing 2846 rows. There are 622 patients, the rows are grouped by patient number and ordered by years after transplant, with each row representing an examination and containing additional covariates.

PTNUM (numeric) Patient identification number
age (numeric) Recipient age at examination (years)
years (numeric) Examination time (years after transplant)
dage (numeric) Age of heart donor (years)
sex (numeric) sex (0=male, 1=female)
pdiag (factor) Primary diagnosis (reason for transplant)
IHD=ischaemic heart disease, IDC=idiopathic dilated cardiomyopathy.
cumrej (numeric) Cumulative number of acute rejection episodes
state (numeric) State at the examination.
State 1 represents no CAV, state 2 is mild/moderate CAV
and state 3 is severe CAV. State 4 indicates death.
firstobs (numeric) 0 = record represents an angiogram or date of death.
1 = record represents transplant (patient's first observation)
statemax (numeric) Maximum observed state so far for this patient (added in version 1.5.1)

Source

Papworth Hospital, U.K.

References

Sharples, L.D. and Jackson, C.H. and Parameshwar, J. and Wallwork, J. and Large, S.R. (2003). Diagnostic accuracy of coronary angiopathy and risk factors for post-heart-transplant cardiac allograft vasculopathy. Transplantation 76(4):679-82


Developer documentation: censoring model object

Description

A list giving information about censored states, their labels in the data and what true states they represent.

Value

ncens

The number of distinct values used for censored observations in the state data supplied to msm.

censor

A vector of length ncens, giving the labels used for censored states in the data.

states

A vector obtained by unlist()ing a list with ncens elements, each giving the set of true states that an observation with this label could be.

index

Index into states for the first state corresponding to each censor, plus an extra length(states)+1.

See Also

msm.object.


Extract model coefficients

Description

Extract the estimated log transition intensities and the corresponding linear effects of each covariate.

Usage

## S3 method for class 'msm'
coef(object, ...)

Arguments

object

A fitted multi-state model object, as returned by msm.

...

(unused) further arguments passed to or from other methods.

Value

If there is no misclassification, coef.msm returns a list of matrices. The first component, labelled logbaseline, is a matrix containing the estimated transition intensities on the log scale with any covariates fixed at their means in the data. Each remaining component is a matrix giving the linear effects of the labelled covariate on the matrix of log intensities.

For misclassification models, coef.msm returns a list of lists. The first component, Qmatrices, is a list of matrices as described in the previous paragraph. The additional component Ematrices is a list of similar format containing the logit-misclassification probabilities and any estimated covariate effects.

Author(s)

C. H. Jackson [email protected]

See Also

msm


Calculate crude initial values for transition intensities

Description

Calculates crude initial values for transition intensities by assuming that the data represent the exact transition times of the Markov process.

Usage

crudeinits.msm(
  formula,
  subject,
  qmatrix,
  data = NULL,
  censor = NULL,
  censor.states = NULL
)

Arguments

formula

A formula giving the vectors containing the observed states and the corresponding observation times. For example,

state ~ time

Observed states should be in the set 1, ...{}, n, where n is the number of states. Note hidden Markov models are not supported by this function.

subject

Vector of subject identification numbers for the data specified by formula. If missing, then all observations are assumed to be on the same subject. These must be sorted so that all observations on the same subject are adjacent.

qmatrix

Matrix of indicators for the allowed transitions. An initial value will be estimated for each value of qmatrix that is greater than zero. Transitions are taken as disallowed for each entry of qmatrix that is 0.

data

An optional data frame in which the variables represented by subject and state can be found.

censor

A state, or vector of states, which indicates censoring. See msm.

censor.states

Specifies the underlying states which censored observations can represent. See msm.

Details

Suppose we want a crude estimate of the transition intensity qrsq_{rs} from state rr to state ss. If we observe nrsn_{rs} transitions from state rr to state ss, and a total of nrn_r transitions from state rr, then qrs/q_{rs} /qrrq_{rr} can be estimated by nrs/nrn_{rs} / n_r. Then, given a total of TrT_r years spent in state rr, the mean sojourn time 1/qrr1 / q_{rr} can be estimated as Tr/nrT_r / n_r. Thus, nrs/Trn_{rs} / T_r is a crude estimate of qrsq_{rs}.

If the data do represent the exact transition times of the Markov process, then these are the exact maximum likelihood estimates.

Observed transitions which are incompatible with the given qmatrix are ignored. Censored states are ignored.

Value

The estimated transition intensity matrix. This can be used as the qmatrix argument to msm.

Author(s)

C. H. Jackson [email protected]

See Also

statetable.msm

Examples

data(cav)
twoway4.q <- rbind(c(-0.5, 0.25, 0, 0.25), c(0.166, -0.498, 0.166, 0.166),
c(0, 0.25, -0.5, 0.25), c(0, 0, 0, 0))
statetable.msm(state, PTNUM, data=cav)
crudeinits.msm(state ~ years, PTNUM, data=cav, qmatrix=twoway4.q)

The delta method

Description

Delta method for approximating the standard error of a transformation g(X)g(X) of a random variable X=(x1,x2,)X = (x_1, x_2, \ldots), given estimates of the mean and covariance matrix of XX.

Usage

deltamethod(g, mean, cov, ses = TRUE)

Arguments

g

A formula representing the transformation. The variables must be labelled x1, x2,...{} For example,

~ 1 / (x1 + x2)

If the transformation returns a vector, then a list of formulae representing (g1,g2,g_1, g_2, \ldots) can be provided, for example

list( ~ x1 + x2, ~ x1 / (x1 + x2) )

mean

The estimated mean of XX

cov

The estimated covariance matrix of XX

ses

If TRUE, then the standard errors of g1(X),g2(X),g_1(X), g_2(X),\ldots are returned. Otherwise the covariance matrix of g(X)g(X) is returned.

Details

The delta method expands a differentiable function of a random variable about its mean, usually with a first-order Taylor approximation, and then takes the variance. For example, an approximation to the covariance matrix of g(X)g(X) is given by

Cov(g(X))=g(μ)Cov(X)[g(μ)]TCov(g(X)) = g'(\mu) Cov(X) [g'(\mu)]^T

where μ\mu is an estimate of the mean of XX. This function uses symbolic differentiation via deriv.

A limitation of this function is that variables created by the user are not visible within the formula g. To work around this, it is necessary to build the formula as a string, using functions such as sprintf, then to convert the string to a formula using as.formula. See the example below.

If you can spare the computational time, bootstrapping is a more accurate method of calculating confidence intervals or standard errors for transformations of parameters. See boot.msm. Simulation from the asymptotic distribution of the MLEs (see e.g. Mandel 2013) is also a convenient alternative.

Value

A vector containing the standard errors of g1(X),g2(X),g_1(X), g_2(X), \ldots or a matrix containing the covariance of g(X)g(X).

Author(s)

C. H. Jackson [email protected]

References

Oehlert, G. W. (1992) A note on the delta method. American Statistician 46(1).

Mandel, M. (2013) Simulation based confidence intervals for functions with complicated derivatives. The American Statistician 67(2):76-81.

Examples

## Simple linear regression, E(y) = alpha + beta x 
x <- 1:100
y <- rnorm(100, 4*x, 5)
toy.lm <- lm(y ~ x)
estmean <- coef(toy.lm)
estvar <- summary(toy.lm)$cov.unscaled * summary(toy.lm)$sigma^2

## Estimate of (1 / (alphahat + betahat))
1 / (estmean[1] + estmean[2])
## Approximate standard error
deltamethod (~ 1 / (x1 + x2), estmean, estvar) 

## We have a variable z we would like to use within the formula.
z <- 1
## deltamethod (~ z / (x1 + x2), estmean, estvar) will not work.
## Instead, build up the formula as a string, and convert to a formula.
form <- sprintf("~ %f / (x1 + x2)", z)
form
deltamethod(as.formula(form), estmean, estvar)

Criteria for comparing two multi-state models with nested state spaces

Description

A modification of Akaike's information criterion, and a leave-one-out likelihood cross-validation criterion, for comparing the predictive ability of two Markov multi-state models with nested state spaces. This is evaluated based on the restricted or aggregated data which the models have in common.

Usage

draic.msm(
  msm.full,
  msm.coarse,
  likelihood.only = FALSE,
  information = c("expected", "observed"),
  tl = 0.95
)

drlcv.msm(
  msm.full,
  msm.coarse,
  tl = 0.95,
  cores = NULL,
  verbose = TRUE,
  outfile = NULL
)

Arguments

msm.full

Model on the bigger state space.

msm.coarse

Model on the smaller state space.

The two models must both be non-hidden Markov models without censored states.

The two models must be fitted to the same datasets, except that the state space of the coarse model must be an aggregated version of the state space of the full model. That is, every state in the full dataset must correspond to a unique state in the coarse dataset. For example, for the full state variable c(1,1,2,2,3,4), the corresponding coarse states could be c(1,1,2,2,2,3), but not c(1,2,3,4,4,4).

The structure of allowed transitions in the coarse model must also be a collapsed version of the big model structure, but no check is currently made for this in the code.

To use these functions, all objects which were used in the calls to fit msm.full and msm.coarse must be in the working environment, for example, datasets and definitions of transition matrices.

likelihood.only

Don't calculate Hessians and trace term (DRAIC).

information

Use observed or expected information in the DRAIC trace term. Expected is the default, and much faster, though is only available for models fitted to pure panel data (all obstype=1 in the call to msm, thus not exact transition times or exact death times)

tl

Width of symmetric tracking interval, by default 0.95 for a 95% interval.

cores

Number of processor cores to use in drlcv for cross-validation by parallel processing. Requires the doParallel package to be installed. If not specified, parallel processing is not used. If cores is set to the string "default", the default methods of makeCluster (on Windows) or registerDoParallel (on Unix-like) are used.

verbose

Print intermediate results of each iteration of cross-validation to the console while running. May not work with parallel processing.

outfile

Output file to print intermediate results of cross-validation. Useful to track execution speed when using parallel processing, where output to the console may not work.

Details

Note that standard AIC can be computed for one or more fitted msm models x,y,... using AIC(x,y,...), and this can be used to compare models fitted to the same data. draic.msm and drlcv.msm are designed for models fitted to data with differently-aggregated state spaces.

The difference in restricted AIC (Liquet and Commenges, 2011), as computed by this function, is defined as

DRAIC=l(γnx)l(θnx)+trace(J(θnx)J(θnx)1J(γnx)J(γnx)1)D_{RAIC} = l(\gamma_n |\mathbf{x}'' ) - l(\theta_n |\mathbf{x}'' ) + trace ( J(\theta_n |\mathbf{x}'')J(\theta_n |\mathbf{x})^{-1} - J(\gamma_n |\mathbf{x}'' )J(\gamma_n |\mathbf{x}' )^{-1})

where γ\gamma and θ\theta are the maximum likelihood estimates of the smaller and bigger models, fitted to the smaller and bigger data, respectively.

l(γnx)l(\gamma_n |x'') represents the likelihood of the simpler model evaluated on the restricted data.

l(θnx)l(\theta_n |x'') represents the likelihood of the complex model evaluated on the restricted data. This is a hidden Markov model, with a misclassification matrix and initial state occupancy probabilities as described by Thom et al (2014).

J()J() are the corresponding (expected or observed, as specified by the user) information matrices.

x\mathbf{x} is the expanded data, to which the bigger model was originally fitted, and x\mathbf{x}' is the data to which the smaller model was originally fitted. x\mathbf{x}'' is the restricted data which the two models have in common. x=x\mathbf{x}'' = \mathbf{x}' in this implementation, so the models are nested.

The difference in likelihood cross-validatory criteria (Liquet and Commenges, 2011) is defined as

DRLCV=1/ni=1nlog(hX(xiγi)/gX(xiθi))D_{RLCV} = 1/n \sum_{i=1}^n \log( h_{X''}(x_i'' | \gamma_{-i}) / g_{X''}(x_i''| \theta_{-i}))

where γi\gamma_{-i} and θi\theta_{-i} are the maximum likelihood estimates from the smaller and bigger models fitted to datasets with subject ii left out, g()g() and h()h() are the densities of the corresponding models, and xix_i'' is the restricted data from subject ii.

Tracking intervals are analogous to confidence intervals, but not strictly the same, since the quantity which D_RAIC aims to estimate, the difference in expected Kullback-Leibler discrepancy for predicting a replicate dataset, depends on the sample size. See the references.

Positive values for these criteria indicate the coarse model is preferred, while negative values indicate the full model is preferred.

Value

A list containing DRAICD_{RAIC} (draic.msm) or DRLCVD_{RLCV} (drlcv.msm), its component terms, and tracking intervals.

Author(s)

C. H. Jackson [email protected], H. H. Z. Thom [email protected]

References

Thom, H. and Jackson, C. and Commenges, D. and Sharples, L. (2015) State selection in multistate models with application to quality of life in psoriatic arthritis. Statistics In Medicine 34(16) 2381 - 2480.

Liquet, B. and Commenges D. (2011) Choice of estimators based on different observations: Modified AIC and LCV criteria. Scandinavian Journal of Statistics; 38:268-287.

See Also

logLik.msm


Developer documentation: model for covariates on misclassification probabilities

Description

A list representing the model for covariates on misclassification probabilities.

Value

npars

Number of covariate effect parameters. This is defined as the number of covariates on misclassification (with factors expanded as contrasts) multiplied by the number of allowed misclassifications in the model.

ndpars

Number of distinct covariate effect parameters, as npars, but after any equality constraints have been applied.

ncovs

Number of covariates on misclassification, with factors expanded as contrasts.

constr

List of equality constraints on these covariate effects, as supplied in the miscconstraint argument to msm.

covlabels

Names / labels of these covariates in the model matrix (see model.matrix.msm).

inits

Initial values for these covariate effects, as a vector formed from the misccovinits list supplied to msm.

covmeans

Means of these covariates in the data (excluding data not required to fit the model, such as observations with missing data in other elements or subjects' last observations). This includes means of 0/1 factor contrasts as well as continuous covariates (for historic reasons, which may not be sensible).

See Also

msm.object.


Expected first passage time

Description

Expected time until first reaching a particular state or set of states in a Markov model.

Usage

efpt.msm(
  x = NULL,
  qmatrix = NULL,
  tostate,
  start = "all",
  covariates = "mean",
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL,
  ...
)

Arguments

x

A fitted multi-state model, as returned by msm.

qmatrix

Instead of x, you can simply supply a transition intensity matrix in qmatrix.

tostate

State, or set of states supplied as a vector, for which to estimate the first passage time into. Can be integer, or character matched to the row names of the Q matrix.

start

Starting state (integer). By default (start="all"), this will return a vector of expected passage times from each state in turn.

Alternatively, this can be used to obtain the expected first passage time from a set of states, rather than single states. To achieve this, state is set to a vector of weights, with length equal to the number of states in the model. These weights should be proportional to the probability of starting in each of the states in the desired set, so that weights of zero are supplied for other states. The function will calculate the weighted average of the expected passage times from each of the corresponding states.

covariates

Covariate values defining the intensity matrix for the fitted model x, as supplied to qmatrix.msm.

ci

If "normal", then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

If "none" (the default) then no confidence interval is calculated.

cl

Width of the symmetric confidence interval, relative to 1.

B

Number of bootstrap replicates.

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

...

Arguments to pass to MatrixExp.

Details

The expected first passage times from each of a set of states i\mathbf{i} to to the remaining set of states i\overline{\mathbf{i}} in the state space, for a model with transition intensity matrix QQ, are

Qi,i11-Q_{\mathbf{i},\mathbf{i}}^{-1} \mathbf{1}

where 1\mathbf{1} is a vector of ones, and Qi,iQ_{\mathbf{i},\mathbf{i}} is the square subset of QQ pertaining to states i\mathbf{i}.

It is equal to the sum of mean sojourn times for all states between the "from" and "to" states in a unidirectional model. If there is non-zero chance of reaching an absorbing state before reaching tostate, then it is infinite. It is trivially zero if the "from" state equals tostate.

This function currently only handles time-homogeneous Markov models. For time-inhomogeneous models it will assume that QQ equals the average intensity matrix over all times and observed covariates. Simulation might be used to handle time dependence.

Note this is the expectation of first passage time, and the confidence intervals are CIs for this mean, not predictive intervals for the first passage time. The full distribution of the first passage time to a set of states can be obtained by setting the rows of the intensity matrix QQ corresponding to that set of states to zero to make a model where those states are absorbing. The corresponding transition probability matrix Exp(Qt)Exp(Qt) then gives the probabilities of having hit or passed that state by a time tt (see the example below). This is implemented in ppass.msm.

Value

A vector of expected first passage times, or "hitting times", from each state to the desired state.

Author(s)

C. H. Jackson [email protected]

References

Norris, J. R. (1997) Markov Chains. Cambridge University Press.

See Also

sojourn.msm, totlos.msm, boot.msm.

Examples

twoway4.q <- rbind(c(-0.5, 0.25, 0, 0.25), c(0.166, -0.498, 0.166, 0.166),
             c(0, 0.25, -0.5, 0.25), c(0, 0, 0, 0))
efpt.msm(qmatrix=twoway4.q, tostate=3)
# given in state 1, expected time to reaching state 3 is infinite
# since may die (state 4) before entering state 3

# If we remove the death state from the model, EFPTs become finite
Q <- twoway4.q[1:3,1:3]; diag(Q) <- 0; diag(Q) <- -rowSums(Q)
efpt.msm(qmatrix=Q, tostate=3)

# Suppose we cannot die or regress while in state 2, can only go to state 3
Q <- twoway4.q; Q[2,4] <- Q[2,1] <- 0; diag(Q) <- 0; diag(Q) <- -rowSums(Q)
efpt.msm(qmatrix=Q, tostate=3)
# The expected time from 2 to 3 now equals the mean sojourn time in 2.
-1/Q[2,2]

# Calculate cumulative distribution of the first passage time
# into state 3 for the following three-state model
Q <- twoway4.q[1:3,1:3]; diag(Q) <- 0; diag(Q) <- -rowSums(Q)
# Firstly form a model where the desired hitting state is absorbing
Q[3,] <- 0
MatrixExp(Q, t=10)[,3]
ppass.msm(qmatrix=Q, tot=10)
# Given in state 1 at time 0, P(hit 3 by time 10) = 0.479
MatrixExp(Q, t=50)[,3]  # P(hit 3 by time 50) = 0.98
ppass.msm(qmatrix=Q, tot=50)

Misclassification probability matrix

Description

Extract the estimated misclassification probability matrix, and corresponding confidence intervals, from a fitted multi-state model at a given set of covariate values.

Usage

ematrix.msm(
  x,
  covariates = "mean",
  ci = c("delta", "normal", "bootstrap", "none"),
  cl = 0.95,
  B = 1000,
  cores = NULL
)

Arguments

x

A fitted multi-state model, as returned by msm

covariates

The covariate values for which to estimate the misclassification probability matrix. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula, or a named list,

list (age = 60, sex = 1)

ci

If "delta" (the default) then confidence intervals are calculated by the delta method, or by simple transformation of the Hessian in the very simplest cases.

If "normal", then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the multinomial-logit-transformed misclassification probabilities and covariate effects, then transforming back.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

Details

Misclassification probabilities and covariate effects are estimated on the multinomial-logit scale by msm. A covariance matrix is estimated from the Hessian of the maximised log-likelihood. From these, the delta method can be used to obtain standard errors of the probabilities on the natural scale at arbitrary covariate values. Confidence intervals are estimated by assuming normality on the multinomial-logit scale.

Value

A list with components:

estimate

Estimated misclassification probability matrix. The rows correspond to true states, and columns observed states.

SE

Corresponding approximate standard errors.

L

Lower confidence limits.

U

Upper confidence limits.

Or if ci="none", then ematrix.msm just returns the estimated misclassification probability matrix.

The default print method for objects returned by ematrix.msm presents estimates and confidence limits. To present estimates and standard errors, do something like

ematrix.msm(x)[c("estimates","SE")]

Author(s)

C. H. Jackson [email protected]

See Also

qmatrix.msm


Developer documentation: misclassification model structure object

Description

A list giving information about the misclassifications assumed in a multi-state model fitted with the ematrix argument of msm. Returned in a fitted msm model object. This information is converted internally to a hmodel object (see hmodel.object) for use in likelihood computations.

Value

nstates

Number of states (same as qmodel$nstates).

npars

Number of allowed misclassifications, equal to sum(imatrix).

imatrix

Indicator matrix for allowed misclassifications. This has (r,s)(r,s) entry 1 if misclassification of true state rr as observed state ss is possible. diagonal entries are arbitrarily set to 0.

ematrix

Matrix of initial values for the misclassification probabilities, supplied as the ematrix argument of msm.

inits

Vector of these initial values, reading across rows of qmatrix and excluding the diagonal and disallowed transitions.

constr

Indicators for equality constraints on baseline misclassification probabilities, taken from the econstraint argument to msm, and mapped if necessary to the set (1,2,3,...)

ndpars

Number of distinct misclassification probabilities, after applying equality constraints.

nipars

Number of initial state occupancy probabilities being estimated. This is zero if est.initprobs=FALSE, otherwise equal to the number of states.

initprobs

Initial state occupancy probabilities, as supplied to msm (initial values before estimation, if est.initprobs=TRUE.)

est.initprobs

Are initial state occupancy probabilities estimated (TRUE or FALSE), as supplied in the est.initprobs argument of msm.

See Also

msm.object,qmodel.object, hmodel.object.


FEV1 measurements from lung transplant recipients

Description

A series of measurements of the forced expiratory volume in one second (FEV1) from lung transplant recipients, from six months onwards after their transplant.

Format

A data frame containing 5896 rows. There are 204 patients, the rows are grouped by patient number and ordered by days after transplant. Each row represents an examination and containing an additional covariate.

ptnum (numeric) Patient identification number.
days (numeric) Examination time (days after transplant).
fev (numeric) Percentage of baseline FEV1. A code of 999 indicates the patient's date of death.
acute (numeric) 0/1 indicator for whether the patient suffered an acute infection or rejection
within 14 days of the visit.

Details

A baseline "normal" FEV1 for each individual is calculated using measurements from the first six months after transplant. After six months, as presented in this dataset, FEV1 is expressed as a percentage of the baseline value.

FEV1 is monitored to diagnose bronchiolitis obliterans syndrome (BOS), a long-term lung function decline, thought to be a form of chronic rejection. Acute rejections and infections also affect the lung function in the short term.

Source

Papworth Hospital, U.K.

References

Jackson, C.H. and Sharples, L.D. Hidden Markov models for the onset and progression of bronchiolitis obliterans syndrome in lung transplant recipients Statistics in Medicine, 21(1): 113–128 (2002).


Calculate tables of hazard ratios for covariates on transition intensities

Description

Hazard ratios are computed by exponentiating the estimated covariate effects on the log-transition intensities. This function is called by summary.msm.

Usage

hazard.msm(x, hazard.scale = 1, cl = 0.95)

Arguments

x

Output from msm representing a fitted multi-state model.

hazard.scale

Vector with same elements as number of covariates on transition rates. Corresponds to the increase in each covariate used to calculate its hazard ratio. Defaults to all 1.

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

Value

A list of tables containing hazard ratio estimates, one table for each covariate. Each table has three columns, containing the hazard ratio, and an approximate upper and lower confidence limit respectively (assuming normality on the log scale), for each Markov chain transition intensity.

Author(s)

C. H. Jackson [email protected]

See Also

msm, summary.msm, odds.msm


Hidden Markov model constructors

Description

These functions are used to specify the distribution of the response conditionally on the underlying state in a hidden Markov model. A list of these function calls, with one component for each state, should be used for the hmodel argument to msm. The initial values for the parameters of the distribution should be given as arguments. Note the initial values should be supplied as literal values - supplying them as variables is currently not supported.

Usage

hmmCat(prob, basecat)

hmmIdent(x)

hmmUnif(lower, upper)

hmmNorm(mean, sd)

hmmLNorm(meanlog, sdlog)

hmmExp(rate)

hmmGamma(shape, rate)

hmmWeibull(shape, scale)

hmmPois(rate)

hmmBinom(size, prob)

hmmBetaBinom(size, meanp, sdp)

hmmNBinom(disp, prob)

hmmBeta(shape1, shape2)

hmmTNorm(mean, sd, lower = -Inf, upper = Inf)

hmmMETNorm(mean, sd, lower, upper, sderr, meanerr = 0)

hmmMEUnif(lower, upper, sderr, meanerr = 0)

hmmT(mean, scale, df)

Arguments

prob

(hmmCat) Vector of probabilities of observing category 1, 2, ...{}, length(prob) respectively. Or the probability governing a binomial or negative binomial distribution.

basecat

(hmmCat) Category which is considered to be the "baseline", so that during estimation, the probabilities are parameterised as probabilities relative to this baseline category. By default, the category with the greatest probability is used as the baseline.

x

(hmmIdent) Code in the data which denotes the exactly-observed state.

lower

(hmmUnif,hmmTNorm,hmmMEUnif) Lower limit for an Uniform or truncated Normal distribution.

upper

(hmmUnif,hmmTNorm,hmmMEUnif) Upper limit for an Uniform or truncated Normal distribution.

mean

(hmmNorm,hmmLNorm,hmmTNorm) Mean defining a Normal, or truncated Normal distribution.

sd

(hmmNorm,hmmLNorm,hmmTNorm) Standard deviation defining a Normal, or truncated Normal distribution.

meanlog

(hmmNorm,hmmLNorm,hmmTNorm) Mean on the log scale, for a log Normal distribution.

sdlog

(hmmNorm,hmmLNorm,hmmTNorm) Standard deviation on the log scale, for a log Normal distribution.

rate

(hmmPois,hmmExp,hmmGamma) Rate of a Poisson, Exponential or Gamma distribution (see dpois, dexp, dgamma).

shape

(hmmPois,hmmExp,hmmGamma) Shape parameter of a Gamma or Weibull distribution (see dgamma, dweibull).

scale

(hmmGamma) Scale parameter of a Gamma distribution (see dgamma), or unstandardised Student t distribution.

size

Order of a Binomial distribution (see dbinom).

meanp

Mean outcome probability in a beta-binomial distribution

sdp

Standard deviation describing the overdispersion of the outcome probability in a beta-binomial distribution

disp

Dispersion parameter of a negative binomial distribution, also called size or order. (see dnbinom).

shape1, shape2

First and second parameters of a beta distribution (see dbeta).

sderr

(hmmMETNorm,hmmUnif) Standard deviation of the Normal measurement error distribution.

meanerr

(hmmMETNorm,hmmUnif) Additional shift in the measurement error, fixed to 0 by default. This may be modelled in terms of covariates.

df

Degrees of freedom of the Student t distribution.

Details

hmmCat represents a categorical response distribution on the set 1, 2, ...{}, length(prob). The Markov model with misclassification is an example of this type of model. The categories in this case are (some subset of) the underlying states.

The hmmIdent distribution is used for underlying states which are observed exactly without error. For hidden Markov models with multiple outcomes, (see hmmMV), the outcome in the data which takes the special hmmIdent value must be the first of the multiple outcomes.

hmmUnif, hmmNorm, hmmLNorm, hmmExp, hmmGamma, hmmWeibull, hmmPois, hmmBinom, hmmTNorm, hmmNBinom and hmmBeta represent Uniform, Normal, log-Normal, exponential, Gamma, Weibull, Poisson, Binomial, truncated Normal, negative binomial and beta distributions, respectively, with parameterisations the same as the default parameterisations in the corresponding base R distribution functions.

hmmT is the Student t distribution with general mean μ\mu, scale σ\sigma and degrees of freedom df. The variance is σ2df/(df+2)\sigma^2 df/(df + 2). Note the t distribution in base R dt is a standardised one with mean 0 and scale 1. These allow any positive (integer or non-integer) df. By default, all three parameters, including df, are estimated when fitting a hidden Markov model, but in practice, df might need to be fixed for identifiability - this can be done using the fixedpars argument to msm.

The hmmMETNorm and hmmMEUnif distributions are truncated Normal and Uniform distributions, but with additional Normal measurement error on the response. These are generalisations of the distributions proposed by Satten and Longini (1996) for modelling the progression of CD4 cell counts in monitoring HIV disease. See medists for density, distribution, quantile and random generation functions for these distributions. See also tnorm for density, distribution, quantile and random generation functions for the truncated Normal distribution.

See the PDF manual ‘msm-manual.pdf’ in the ‘doc’ subdirectory for algebraic definitions of all these distributions. New hidden Markov model response distributions can be added to msm by following the instructions in Section 2.17.1.

Parameters which can be modelled in terms of covariates, on the scale of a link function, are as follows.

PARAMETER NAME LINK FUNCTION
mean identity
meanlog identity
rate log
scale log
meanerr identity
meanp logit
prob logit or multinomial logit

Parameters basecat, lower, upper, size, meanerr are fixed at their initial values. All other parameters are estimated while fitting the hidden Markov model, unless the appropriate fixedpars argument is supplied to msm.

For categorical response distributions (hmmCat) the outcome probabilities initialized to zero are fixed at zero, and the probability corresponding to basecat is fixed to one minus the sum of the remaining probabilities. These remaining probabilities are estimated, and can be modelled in terms of covariates via multinomial logistic regression (relative to basecat).

Value

Each function returns an object of class hmmdist, which is a list containing information about the model. The only component which may be useful to end users is r, a function of one argument n which returns a random sample of size n from the given distribution.

Author(s)

C. H. Jackson [email protected]

References

Satten, G.A. and Longini, I.M. Markov chains with measurement error: estimating the 'true' course of a marker of the progression of human immunodeficiency virus disease (with discussion) Applied Statistics 45(3): 275-309 (1996).

Jackson, C.H. and Sharples, L.D. Hidden Markov models for the onset and progresison of bronchiolitis obliterans syndrome in lung transplant recipients Statistics in Medicine, 21(1): 113–128 (2002).

Jackson, C.H., Sharples, L.D., Thompson, S.G. and Duffy, S.W. and Couto, E. Multi-state Markov models for disease progression with classification error. The Statistician, 52(2): 193–209 (2003).

See Also

msm


Multivariate hidden Markov models

Description

Constructor for a a multivariate hidden Markov model (HMM) where each of the n variables observed at the same time has a (potentially different) standard univariate distribution conditionally on the underlying state. The n outcomes are independent conditionally on the hidden state.

Usage

hmmMV(...)

Arguments

...

The number of arguments supplied should equal the maximum number of observations made at one time. Each argument represents the univariate distribution of that outcome conditionally on the hidden state, and should be the result of calling a univariate hidden Markov model constructor (see hmm-dists).

Details

If a particular state in a HMM has such an outcome distribution, then a call to hmmMV is supplied as the corresponding element of the hmodel argument to msm. See Example 2 below.

A multivariate HMM where multiple outcomes at the same time are generated from the same distribution is specified in the same way as the corresponding univariate model, so that hmmMV is not required. The outcome data are simply supplied as a matrix instead of a vector. See Example 1 below.

The outcome data for such models are supplied as a matrix, with number of columns equal to the maximum number of arguments supplied to the hmmMV calls for each state. If some but not all of the variables are missing (NA) at a particular time, then the observed data at that time still contribute to the likelihood. The missing data are assumed to be missing at random. The Viterbi algorithm may be used to predict the missing values given the fitted model and the observed data.

Typically the outcome model for each state will be from the same family or set of families, but with different parameters. Theoretically, different numbers of distributions may be supplied for different states. If a particular state has fewer outcomes than the maximum, then the data for that state are taken from the first columns of the response data matrix. However this is not likely to be a useful model, since the number of observations will probably give information about the underlying state, violating the missing at random assumption.

Models with outcomes that are dependent conditionally on the hidden state (e.g. correlated multivariate normal observations) are not currently supported.

Value

A list of objects, each of class hmmdist as returned by the univariate HMM constructors documented in hmm-dists. The whole list has class hmmMVdist, which inherits from hmmdist.

Author(s)

C. H. Jackson [email protected]

References

Jackson, C. H., Su, L., Gladman, D. D. and Farewell, V. T. (2015) On modelling minimal disease activity. Arthritis Care and Research (early view).

See Also

hmm-dists,msm

Examples

## Simulate data from a Markov model 
nsubj <- 30; nobspt <- 5
sim.df <- data.frame(subject = rep(1:nsubj, each=nobspt),
                     time = seq(0, 20, length=nobspt))
set.seed(1)
two.q <- rbind(c(-0.1, 0.1), c(0, 0))
dat <- simmulti.msm(sim.df[,1:2], qmatrix=two.q, drop.absorb=FALSE)

### EXAMPLE 1
## Generate two observations at each time from the same outcome
## distribution:
## Bin(40, 0.1) for state 1, Bin(40, 0.5) for state 2
dat$obs1[dat$state==1] <- rbinom(sum(dat$state==1), 40, 0.1)
dat$obs2[dat$state==1] <- rbinom(sum(dat$state==1), 40, 0.1)
dat$obs1[dat$state==2] <- rbinom(sum(dat$state==2), 40, 0.5)
dat$obs2[dat$state==2] <- rbinom(sum(dat$state==2), 40, 0.5)
dat$obs <- cbind(obs1 = dat$obs1, obs2 = dat$obs2)

## Fitted model should approximately recover true parameters 
msm(obs ~ time, subject=subject, data=dat, qmatrix=two.q,
    hmodel = list(hmmBinom(size=40, prob=0.2),
                  hmmBinom(size=40, prob=0.2)))

### EXAMPLE 2
## Generate two observations at each time from different
## outcome distributions:
## Bin(40, 0.1) and Bin(40, 0.2) for state 1, 
dat$obs1 <- dat$obs2 <- NA
dat$obs1[dat$state==1] <- rbinom(sum(dat$state==1), 40, 0.1)
dat$obs2[dat$state==1] <- rbinom(sum(dat$state==1), 40, 0.2)

## Bin(40, 0.5) and Bin(40, 0.6) for state 2
dat$obs1[dat$state==2] <- rbinom(sum(dat$state==2), 40, 0.6)
dat$obs2[dat$state==2] <- rbinom(sum(dat$state==2), 40, 0.5)
dat$obs <- cbind(obs1 = dat$obs1, obs2 = dat$obs2)

## Fitted model should approximately recover true parameters 
msm(obs ~ time, subject=subject, data=dat, qmatrix=two.q,   
    hmodel = list(hmmMV(hmmBinom(size=40, prob=0.3),
                        hmmBinom(size=40, prob=0.3)),                 
                 hmmMV(hmmBinom(size=40, prob=0.3),
                       hmmBinom(size=40, prob=0.3))),
    control=list(maxit=10000))

Developer documentation: hidden Markov model structure object

Description

A list giving information about the models for the outcome data conditionally on the states of a hidden Markov model. Used in internal computations, and returned in a fitted msm model object.

Value

hidden

TRUE for hidden Markov models, FALSE otherwise.

nstates

Number of states, the same as qmodel$nstates.

fitted

TRUE if the parameter values in pars are the maximum likelihood estimates, FALSE if they are the initial values.

models

The outcome distribution for each hidden state. A vector of length nstates whose rrth entry is the index of the state rr outcome distributions in the vector of supported distributions. The vector of supported distributions is given in full by msm:::.msm.HMODELS: the first few are 1 for categorical outcome, 2 for identity, 3 for uniform and 4 for normal.

labels

String identifying each distribution in models.

npars

Vector of length nstates giving the number of parameters in each outcome distribution, excluding covariate effects.

nipars

Number of initial state occupancy probabilities being estimated. This is zero if est.initprobs=FALSE, otherwise equal to the number of states.

totpars

Total number of parameters, equal to sum(npars).

pars

A vector of length totpars, made from concatenating a list of length nstates whose rrth component is vector of the parameters for the state rr outcome distribution.

plabs

List with the names of the parameters in pars.

parstate

A vector of length totpars, whose iith element is the state corresponding to the iith parameter.

firstpar

A vector of length nstates giving the index in pars of the first parameter for each state.

locpars

Index in pars of parameters which can have covariates on them.

initprobs

Initial state occupancy probabilities, as supplied to msm (initial values before estimation, if est.initprobs=TRUE.)

est.initprobs

Are initial state occupancy probabilities estimated (TRUE or FALSE), as supplied in the est.initprobs argument of msm.

ncovs

Number of covariate effects per parameter in pars, with, e.g. factor contrasts expanded.

coveffect

Vector of covariate effects, of length sum(ncovs).

covlabels

Labels of these effects.

coveffstate

Vector indicating state corresponding to each element of coveffect.

ncoveffs

Number of covariate effects on HMM outcomes, equal to sum(ncovs).

nicovs

Vector of length nstates-1 giving the number of covariate effects on each initial state occupancy probability (log relative to the baseline probability).

icoveffect

Vector of length sum(nicovs) giving covariate effects on initial state occupancy probabilities.

nicoveffs

Number of covariate effects on initial state occupancy probabilities, equal to sum(nicovs).

constr

Constraints on (baseline) hidden Markov model outcome parameters, as supplied in the hconstraint argument of msm, excluding covariate effects, converted to a vector and mapped to the set 1,2,3,... if necessary.

covconstr

Vector of constraints on covariate effects in hidden Markov outcome models, as supplied in the hconstraint argument of msm, excluding baseline parameters, converted to a vector and mapped to the set 1,2,3,... if necessary.

ranges

Matrix of range restrictions for HMM parameters, including those given to the hranges argument to msm.

foundse

TRUE if standard errors are available for the estimates.

initpmat

Matrix of initial state occupancy probabilities with one row for each subject (estimated if est.initprobs=TRUE).

ci

Confidence intervals for baseline HMM outcome parameters.

covci

Confidence intervals for covariate effects in HMM outcome models.

See Also

msm.object,qmodel.object, emodel.object.


Convert a hmodel object to HMM constructor function calls

Description

Convert a hmodel object to HMM constructor function calls

Usage

hmodel2list(hmodel, hmmdist = TRUE)

Arguments

hmodel

A list of class hmodel, as returned in the hmodel component of the fitted model object from msm.

hmmdist

TRUE or FALSE (see "Value" section).

Value

If hmmdist=TRUE, returns a list of objects of class hmmdist. These are the kind of objects returned by HMM constructor functions such as hmmNorm, hmmPois etc. Therefore the list can be passed as the hmodel argument to msm.

If hmmdist=FALSE, returns a list comprised of the corresponding input arguments for the constructor functions, i.e. parameter values of HMM emission distributions. The list has one element per state. Each of these elements has one element per parameter (for univariate HMMs), or one element per outcome distribution, which in turn has one element per parameter (for multivariate HMMs).

Author(s)

Will Hulme https://github.com/wjchulme and Chris Jackson.


Extract model log-likelihood

Description

Extract the log-likelihood and the number of parameters of a model fitted with msm.

Usage

## S3 method for class 'msm'
logLik(object, by.subject = FALSE, ...)

Arguments

object

A fitted multi-state model object, as returned by msm.

by.subject

Return vector of subject-specific log-likelihoods, which should sum to the total log-likelihood.

...

(unused) further arguments passed to or from other methods.

Value

The log-likelihood of the model represented by 'object' evaluated at the maximum likelihood estimates.

Akaike's information criterion can also be computed using AIC(object).

Author(s)

C. H. Jackson [email protected]

See Also

msm,lrtest.msm.


Likelihood ratio test

Description

Likelihood ratio test between two or more fitted multi-state models

Usage

lrtest.msm(...)

Arguments

...

Two or more fitted multi-state models, as returned by msm, ordered by increasing numbers of parameters.

Value

A matrix with three columns, giving the likelihood ratio statistic, difference in degrees of freedom and the chi-squared p-value for a comparison of the first model supplied with each subsequent model.

Warning

The comparison between models will only be valid if they are fitted to the same dataset. This may be a problem if there are missing values and R's default of 'na.action = na.omit' is used.

The likelihood ratio statistic only has the indicated chi-squared distribution if the models are nested. An alternative for comparing non-nested models is Akaike's information criterion. This can be computed for one or more fitted msm models x,y,... using AIC(x,y,...).

See Also

logLik.msm,msm


Matrix exponential

Description

Calculates the exponential of a square matrix.

Usage

MatrixExp(mat, t = 1, method = NULL, ...)

Arguments

mat

A square matrix

t

An optional scaling factor for mat. If a vector is supplied, then an array of matrices is returned with different scaling factors.

method

Under the default of NULL, this simply wraps the expm function from the expm package. This is recommended. Options to expm can be supplied to MatrixExp, including method.

Otherwise, for backwards compatibility, the following options, which use code in the msm package, are available: "pade" for a Pade approximation method, "series" for the power series approximation, or "analytic" for the analytic formulae for simpler Markov model intensity matrices (see below). These options are only used if mat has repeated eigenvalues, thus the usual eigen-decomposition method cannot be used.

...

Arguments to pass to expm.

Details

See the expm documentation for details of the algorithms it uses.

Generally the exponential EE of a square matrix MM can often be calculated as

E=Uexp(D)U1E = U \exp(D) U^{-1}

where DD is a diagonal matrix with the eigenvalues of MM on the diagonal, exp(D)\exp(D) is a diagonal matrix with the exponentiated eigenvalues of MM on the diagonal, and UU is a matrix whose columns are the eigenvectors of MM.

This method of calculation is used if "pade" or "series" is supplied but MM has distinct eigenvalues. I If MM has repeated eigenvalues, then its eigenvector matrix may be non-invertible. In this case, the matrix exponential is calculated using the Pade approximation defined by Moler and van Loan (2003), or the less robust power series approximation,

exp(M)=I+M+M2/2+M3/3!+M4/4!+...\exp(M) = I + M + M^2/2 + M^3 / 3! + M^4 / 4! + ...

For a continuous-time homogeneous Markov process with transition intensity matrix QQ, the probability of occupying state ss at time u+tu + t conditional on occupying state rr at time uu is given by the (r,s)(r,s) entry of the matrix exp(tQ)\exp(tQ).

If mat is a valid transition intensity matrix for a continuous-time Markov model (i.e. diagonal entries non-positive, off-diagonal entries non-negative, rows sum to zero), then for certain simpler model structures, there are analytic formulae for the individual entries of the exponential of mat. These structures are listed in the PDF manual and the formulae are coded in the msm source file src/analyticp.c. These formulae are only used if method="analytic". This is more efficient, but it is not the default in MatrixExp because the code is not robust to extreme values. However it is the default when calculating likelihoods for models fitted by msm.

The implementation of the Pade approximation used by method="pade" was taken from JAGS by Martyn Plummer (https://mcmc-jags.sourceforge.io).

Value

The exponentiated matrix exp(mat)\exp(mat). Or, if t is a vector of length 2 or more, an array of exponentiated matrices.

References

Cox, D. R. and Miller, H. D. The theory of stochastic processes, Chapman and Hall, London (1965)

Moler, C and van Loan, C (2003). Nineteen dubious ways to compute the exponential of a matrix, twenty-five years later. SIAM Review 45, 3–49.


Measurement error distributions

Description

Truncated Normal and Uniform distributions, where the response is also subject to a Normally distributed measurement error.

Usage

dmenorm(
  x,
  mean = 0,
  sd = 1,
  lower = -Inf,
  upper = Inf,
  sderr = 0,
  meanerr = 0,
  log = FALSE
)

pmenorm(
  q,
  mean = 0,
  sd = 1,
  lower = -Inf,
  upper = Inf,
  sderr = 0,
  meanerr = 0,
  lower.tail = TRUE,
  log.p = FALSE
)

qmenorm(
  p,
  mean = 0,
  sd = 1,
  lower = -Inf,
  upper = Inf,
  sderr = 0,
  meanerr = 0,
  lower.tail = TRUE,
  log.p = FALSE
)

rmenorm(n, mean = 0, sd = 1, lower = -Inf, upper = Inf, sderr = 0, meanerr = 0)

dmeunif(x, lower = 0, upper = 1, sderr = 0, meanerr = 0, log = FALSE)

pmeunif(
  q,
  lower = 0,
  upper = 1,
  sderr = 0,
  meanerr = 0,
  lower.tail = TRUE,
  log.p = FALSE
)

qmeunif(
  p,
  lower = 0,
  upper = 1,
  sderr = 0,
  meanerr = 0,
  lower.tail = TRUE,
  log.p = FALSE
)

rmeunif(n, lower = 0, upper = 1, sderr = 0, meanerr = 0)

Arguments

x, q

vector of quantiles.

mean

vector of means.

sd

vector of standard deviations.

lower

lower truncation point.

upper

upper truncation point.

sderr

Standard deviation of measurement error distribution.

meanerr

Optional shift for the measurement error distribution.

log, log.p

logical; if TRUE, probabilities pp are given as log(p)\log(p), or log density is returned.

lower.tail

logical; if TRUE (default), probabilities are P[X<=x]P[X <= x], otherwise, P[X>x]P[X > x].

p

vector of probabilities.

n

number of observations. If length(n) > 1, the length is taken to be the number required.

Details

The normal distribution with measurement error has density

Φ(u,μ2,σ3)Φ(l,μ2,σ3)Φ(u,μ2,σ3)Φ(l,μ2,σ3)ϕ(x,μ0+μϵ,σ2)\frac{\Phi(u, \mu_2, \sigma_3) - \Phi(l, \mu_2, \sigma_3)}{\Phi(u, \mu_2, \sigma_3) - \Phi(l, \mu_2, \sigma_3)} \phi(x, \mu_0 + \mu_\epsilon, \sigma_2)

where

σ22=σ02+σϵ2,\sigma_2^2 = \sigma_0^2 + \sigma_\epsilon^2,

σ3=σ0σϵ/σ2,\sigma_3 = \sigma_0 \sigma_\epsilon / \sigma_2,

μ2=(xμϵ)σ02+μ0σϵ2,\mu_2 = (x - \mu_\epsilon) \sigma_0^2 + \mu_0 \sigma_\epsilon^2,

μ0\mu_0 is the mean of the original Normal distribution before truncation,
σ0\sigma_0 is the corresponding standard deviation,
uu is the upper truncation point,
ll is the lower truncation point,
σϵ\sigma_\epsilon is the standard deviation of the additional measurement error,
μϵ\mu_\epsilon is the mean of the measurement error (usually 0).
ϕ(x)\phi(x) is the density of the corresponding normal distribution, and
Φ(x)\Phi(x) is the distribution function of the corresponding normal distribution.

The uniform distribution with measurement error has density

(Φ(x,μϵ+l,σϵ)Φ(x,μϵ+u,σϵ))(\Phi(x, \mu_\epsilon+l, \sigma_\epsilon) - \Phi(x, \mu_\epsilon+u, \sigma_\epsilon))

/(ul)/ (u - l)

These are calculated from the original truncated Normal or Uniform density functions f(.μ,σ,l,u)f(. | \mu, \sigma, l, u) as

f(yμ,σ,l,u)ϕ(x,y+μϵ,σϵ)dy\int f(y | \mu, \sigma, l, u) \phi(x, y + \mu_\epsilon, \sigma_\epsilon) dy

If sderr and meanerr are not specified they assume the default values of 0, representing no measurement error variance, and no constant shift in the measurement error, respectively.

Therefore, for example with no other arguments, dmenorm(x), is simply equivalent to dtnorm(x), which in turn is equivalent to dnorm(x).

These distributions were used by Satten and Longini (1996) for CD4 cell counts conditionally on hidden Markov states of HIV infection, and later by Jackson and Sharples (2002) for FEV1 measurements conditionally on states of chronic lung transplant rejection.

These distribution functions are just provided for convenience, and are not optimised for numerical accuracy or speed. To fit a hidden Markov model with these response distributions, use a hmmMETNorm or hmmMEUnif constructor. See the hmm-dists help page for further details.

Value

dmenorm, dmeunif give the density, pmenorm, pmeunif give the distribution function, qmenorm, qmeunif give the quantile function, and rmenorm, rmeunif generate random deviates, for the Normal and Uniform versions respectively.

Author(s)

C. H. Jackson [email protected]

References

Satten, G.A. and Longini, I.M. Markov chains with measurement error: estimating the 'true' course of a marker of the progression of human immunodeficiency virus disease (with discussion) Applied Statistics 45(3): 275-309 (1996)

Jackson, C.H. and Sharples, L.D. Hidden Markov models for the onset and progression of bronchiolitis obliterans syndrome in lung transplant recipients Statistics in Medicine, 21(1): 113–128 (2002).

See Also

dnorm, dunif, dtnorm

Examples

## what does the distribution look like?
x <- seq(50, 90, by=1)
plot(x, dnorm(x, 70, 10), type="l", ylim=c(0,0.06)) ## standard Normal
lines(x, dtnorm(x, 70, 10, 60, 80), type="l")       ## truncated Normal
## truncated Normal with small measurement error
lines(x, dmenorm(x, 70, 10, 60, 80, sderr=3), type="l")

Extract original data from msm objects.

Description

Extract the data from a multi-state model fitted with msm.

Usage

## S3 method for class 'msm'
model.frame(formula, agg = FALSE, ...)

## S3 method for class 'msm'
model.matrix(object, model = "intens", state = 1, ...)

Arguments

formula

A fitted multi-state model object, as returned by msm.

agg

Return the model frame in the efficient aggregated form used to calculate the likelihood internally for non-hidden Markov models. This has one row for each unique combination of from-state, to-state, time lag, covariate value and observation type. The variable named "(nocc)" counts how many observations of that combination there are in the original data.

...

Further arguments (not used).

object

A fitted multi-state model object, as returned by msm.

model

"intens" to return the design matrix for covariates on intensities, "misc" for misclassification probabilities, "hmm" for a general hidden Markov model, and "inits" for initial state probabilities in hidden Markov models.

state

State corresponding to the required covariate design matrix in a hidden Markov model.

Value

model.frame returns a data frame with all the original variables used for the model fit, with any missing data removed (see na.action in msm). The state, time, subject, obstype and obstrue variables are named "(state)", "(time)", "(subject)", "(obstype)" and "(obstrue)" respectively (note the brackets). A variable called "(obs)" is the observation number from the original data before any missing data were dropped. The variable "(pcomb)" is used for computing the likelihood for hidden Markov models, and identifies which distinct time difference, obstype and covariate values (thus which distinct interval transition probability matrix) each observation corresponds to.

The model frame object has some other useful attributes, including "usernames" giving the user's original names for these variables (used for model refitting, e.g. in bootstrapping or cross validation) and "covnames" identifying which ones are covariates.

model.matrix returns a design matrix for a part of the model that includes covariates. The required part is indicated by the "model" argument.

For time-inhomogeneous models fitted with "pci", these datasets will have imputed observations at each time change point, indicated where the variable "(pci.imp)" in the model frame is 1. The model matrix for intensities will have factor contrasts for the timeperiod covariate.

Author(s)

C. H. Jackson [email protected]

See Also

msm, model.frame, model.matrix.


Multi-state Markov and hidden Markov models in continuous time

Description

Fit a continuous-time Markov or hidden Markov multi-state model by maximum likelihood. Observations of the process can be made at arbitrary times, or the exact times of transition between states can be known. Covariates can be fitted to the Markov chain transition intensities or to the hidden Markov observation process.

Usage

msm(
  formula,
  subject = NULL,
  data = list(),
  qmatrix,
  gen.inits = FALSE,
  ematrix = NULL,
  hmodel = NULL,
  obstype = NULL,
  obstrue = NULL,
  covariates = NULL,
  covinits = NULL,
  constraint = NULL,
  misccovariates = NULL,
  misccovinits = NULL,
  miscconstraint = NULL,
  hcovariates = NULL,
  hcovinits = NULL,
  hconstraint = NULL,
  hranges = NULL,
  qconstraint = NULL,
  econstraint = NULL,
  initprobs = NULL,
  est.initprobs = FALSE,
  initcovariates = NULL,
  initcovinits = NULL,
  deathexact = NULL,
  death = NULL,
  exacttimes = FALSE,
  censor = NULL,
  censor.states = NULL,
  pci = NULL,
  phase.states = NULL,
  phase.inits = NULL,
  subject.weights = NULL,
  cl = 0.95,
  fixedpars = NULL,
  center = TRUE,
  opt.method = "optim",
  hessian = NULL,
  use.deriv = TRUE,
  use.expm = TRUE,
  analyticp = TRUE,
  na.action = na.omit,
  ...
)

Arguments

formula

A formula giving the vectors containing the observed states and the corresponding observation times. For example,

state ~ time

Observed states should be numeric variables in the set 1, ...{}, n, where n is the number of states. Factors are allowed only if their levels are called "1", ...{}, "n".

The times can indicate different types of observation scheme, so be careful to choose the correct obstype.

For hidden Markov models, state refers to the outcome variable, which need not be a discrete state. It may also be a matrix, giving multiple observations at each time (see hmmMV).

subject

Vector of subject identification numbers for the data specified by formula. If missing, then all observations are assumed to be on the same subject. These must be sorted so that all observations on the same subject are adjacent.

data

Optional data frame in which to interpret the variables supplied in formula, subject, covariates, misccovariates, hcovariates, obstype and obstrue.

qmatrix

Matrix which indicates the allowed transitions in the continuous-time Markov chain, and optionally also the initial values of those transitions. If an instantaneous transition is not allowed from state rr to state ss, then qmatrix should have (r,s)(r,s) entry 0, otherwise it should be non-zero.

If supplying initial values yourself, then the non-zero entries should be those values. If using gen.inits=TRUE then the non-zero entries can be anything you like (conventionally 1). Any diagonal entry of qmatrix is ignored, as it is constrained to be equal to minus the sum of the rest of the row.

For example,

rbind( c( 0, 0.1, 0.01 ), c( 0.1, 0, 0.2 ), c( 0, 0, 0 ) )

represents a 'health - disease - death' model, with initial transition intensities 0.1 from health to disease, 0.01 from health to death, 0.1 from disease to health, and 0.2 from disease to death.

If the states represent ordered levels of severity of a disease, then this matrix should usually only allow transitions between adjacent states. For example, if someone was observed in state 1 ("mild") at their first observation, followed by state 3 ("severe") at their second observation, they are assumed to have passed through state 2 ("moderate") in between, and the 1,3 entry of qmatrix should be zero.

The initial intensities given here are with any covariates set to their means in the data (or set to zero, if center = FALSE). If any intensities are constrained to be equal using qconstraint, then the initial value is taken from the first of these (reading across rows).

gen.inits

If TRUE, then initial values for the transition intensities are generated automatically using the method in crudeinits.msm. The non-zero entries of the supplied qmatrix are assumed to indicate the allowed transitions of the model. This is not available for hidden Markov models, including models with misclassified states.

ematrix

If misclassification between states is to be modelled, this should be a matrix of initial values for the misclassification probabilities. The rows represent underlying states, and the columns represent observed states. If an observation of state ss is not possible when the subject occupies underlying state rr, then ematrix should have (r,s)(r,s) entry 0. Otherwise ematrix should have (r,s)(r,s) entry corresponding to the probability of observing ss conditionally on occupying true state rr. The diagonal of ematrix is ignored, as rows are constrained to sum to 1. For example,

rbind( c( 0, 0.1, 0 ), c( 0.1, 0, 0.1 ), c( 0, 0.1, 0 ) )

represents a model in which misclassifications are only permitted between adjacent states.

If any probabilities are constrained to be equal using econstraint, then the initial value is taken from the first of these (reading across rows).

For an alternative way of specifying misclassification models, see hmodel.

hmodel

Specification of the hidden Markov model (HMM). This should be a list of return values from HMM constructor functions. Each element of the list corresponds to the outcome model conditionally on the corresponding underlying state. Univariate constructors are described in thehmm-dists help page. These may also be grouped together to specify a multivariate HMM with a set of conditionally independent univariate outcomes at each time, as described in hmmMV.

For example, consider a three-state hidden Markov model. Suppose the observations in underlying state 1 are generated from a Normal distribution with mean 100 and standard deviation 16, while observations in underlying state 2 are Normal with mean 54 and standard deviation 18. Observations in state 3, representing death, are exactly observed, and coded as 999 in the data. This model is specified as

hmodel = list(hmmNorm(mean=100, sd=16), hmmNorm(mean=54, sd=18), hmmIdent(999))

The mean and standard deviation parameters are estimated starting from these initial values. If multiple parameters are constrained to be equal using hconstraint, then the initial value is taken from the value given on the first occasion that parameter appears in hmodel.

See the hmm-dists help page for details of the constructor functions for each univariate distribution.

A misclassification model, that is, a hidden Markov model where the outcomes are misclassified observations of the underlying states, can either be specified using a list of hmmCat or hmmIdent objects, or by using an ematrix.

For example,

ematrix = rbind( c( 0, 0.1, 0, 0 ), c( 0.1, 0, 0.1, 0 ), c( 0, 0.1, 0, 0), c( 0, 0, 0, 0) )

is equivalent to

hmodel = list( hmmCat(prob=c(0.9, 0.1, 0, 0)), hmmCat(prob=c(0.1, 0.8, 0.1, 0)), hmmCat(prob=c(0, 0.1, 0.9, 0)), hmmIdent())

obstype

A vector specifying the observation scheme for each row of the data. This can be included in the data frame data along with the state, time, subject IDs and covariates. Its elements should be either 1, 2 or 3, meaning as follows:

1

An observation of the process at an arbitrary time (a "snapshot" of the process, or "panel-observed" data). The states are unknown between observation times.

2

An exact transition time, with the state at the previous observation retained until the current observation. An observation may represent a transition to a different state or a repeated observation of the same state (e.g. at the end of follow-up). Note that if all transition times are known, more flexible models could be fitted with packages other than msm - see the note under exacttimes.

Note also that if the previous state was censored using censor, for example known only to be state 1 or state 2, then obstype 2 means that either state 1 is retained or state 2 is retained until the current observation - this does not allow for a change of state in the middle of the observation interval.

3

An exact transition time, but the state at the instant before entering this state is unknown. A common example is death times in studies of chronic diseases.

If obstype is not specified, this defaults to all 1. If obstype is a single number, all observations are assumed to be of this type. The obstype value for the first observation from each subject is not used.

This is a generalisation of the deathexact and exacttimes arguments to allow different schemes per observation. obstype overrides both deathexact and exacttimes.

exacttimes=TRUE specifies that all observations are of obstype 2.

deathexact = death.states specifies that all observations of death.states are of type 3. deathexact = TRUE specifies that all observations in the final absorbing state are of type 3.

obstrue

In misclassification models specified with ematrix, obstrue is a vector of logicals (TRUE or FALSE) or numerics (1 or 0) specifying which observations (TRUE, 1) are observations of the underlying state without error, and which (FALSE, 0) are realisations of a hidden Markov model.

In HMMs specified with hmodel, where the hidden state is known at some times, if obstrue is supplied it is assumed to contain the actual true state data. Elements of obstrue at times when the hidden state is unknown are set to NA. This allows the information from HMM outcomes generated conditionally on the known state to be included in the model, thus improving the estimation of the HMM outcome distributions.

HMMs where the true state is known to be within a specific set at specific times can be defined with a combination of censor and obstrue. In these models, a code is defined for the state outcome (see censor), and obstrue is set to 1 for observations where the true state is known to be one of the elements of censor.states at the corresponding time.

covariates

A formula or a list of formulae representing the covariates on the transition intensities via a log-linear model. If a single formula is supplied, like

covariates = ~ age + sex + treatment

then these covariates are assumed to apply to all intensities. If a named list is supplied, then this defines a potentially different model for each named intensity. For example,

covariates = list("1-2" = ~ age, "2-3" = ~ age + treatment)

specifies an age effect on the state 1 - state 2 transition, additive age and treatment effects on the state 2 - state 3 transition, but no covariates on any other transitions that are allowed by the qmatrix.

If covariates are time dependent, they are assumed to be constant in between the times they are observed, and the transition probability between a pair of times (t1,t2)(t1, t2) is assumed to depend on the covariate value at t1t1.

covinits

Initial values for log-linear effects of covariates on the transition intensities. This should be a named list with each element corresponding to a covariate. A single element contains the initial values for that covariate on each transition intensity, reading across the rows in order. For a pair of effects constrained to be equal, the initial value for the first of the two effects is used.

For example, for a model with the above qmatrix and age and sex covariates, the following initialises all covariate effects to zero apart from the age effect on the 2-1 transition, and the sex effect on the 1-3 transition. covinits = list(sex=c(0, 0, 0.1, 0), age=c(0, 0.1, 0, 0))

For factor covariates, name each level by concatenating the name of the covariate with the level name, quoting if necessary. For example, for a covariate agegroup with three levels 0-15, 15-60, 60-, use something like

covinits = list("agegroup15-60"=c(0, 0.1, 0, 0), "agegroup60-"=c(0.1, 0.1, 0, 0))

If not specified or wrongly specified, initial values are assumed to be zero.

constraint

A list of one numeric vector for each named covariate. The vector indicates which covariate effects on intensities are constrained to be equal. Take, for example, a model with five transition intensities and two covariates. Specifying

constraint = list (age = c(1,1,1,2,2), treatment = c(1,2,3,4,5))

constrains the effect of age to be equal for the first three intensities, and equal for the fourth and fifth. The effect of treatment is assumed to be different for each intensity. Any vector of increasing numbers can be used as indicators. The intensity parameters are assumed to be ordered by reading across the rows of the transition matrix, starting at the first row, ignoring the diagonals.

Negative elements of the vector can be used to indicate that particular covariate effects are constrained to be equal to minus some other effects. For example:

constraint = list (age = c(-1,1,1,2,-2), treatment = c(1,2,3,4,5))

constrains the second and third age effects to be equal, the first effect to be minus the second, and the fifth age effect to be minus the fourth. For example, it may be realisitic that the effect of a covariate on the "reverse" transition rate from state 2 to state 1 is minus the effect on the "forward" transition rate, state 1 to state 2. Note that it is not possible to specify exactly which of the covariate effects are constrained to be positive and which negative. The maximum likelihood estimation chooses the combination of signs which has the higher likelihood.

For categorical covariates, defined as factors, specify constraints as follows:

list(..., covnameVALUE1 = c(...), covnameVALUE2 = c(...), ...)

where covname is the name of the factor, and VALUE1, VALUE2, ... are the labels of the factor levels (usually excluding the baseline, if using the default contrasts).

Make sure the contrasts option is set appropriately, for example, the default

options(contrasts=c(contr.treatment, contr.poly))

sets the first (baseline) level of unordered factors to zero, then the baseline level is ignored in this specification.

To assume no covariate effect on a certain transition, use the fixedpars argument to fix it at its initial value (which is zero by default) during the optimisation.

misccovariates

A formula representing the covariates on the misclassification probabilities, analogously to covariates, via multinomial logistic regression. Only used if the model is specified using ematrix, rather than hmodel.

This must be a single formula - lists are not supported, unlike covariates. If a different model on each probability is required, include all covariates in this formula, and use fixedpars to fix some of their effects (for particular probabilities) at their default initial values of zero.

misccovinits

Initial values for the covariates on the misclassification probabilities, defined in the same way as covinits. Only used if the model is specified using ematrix.

miscconstraint

A list of one vector for each named covariate on misclassification probabilities. The vector indicates which covariate effects on misclassification probabilities are constrained to be equal, analogously to constraint. Only used if the model is specified using ematrix.

hcovariates

List of formulae the same length as hmodel, defining any covariates governing the hidden Markov outcome models. The covariates operate on a suitably link-transformed linear scale, for example, log scale for a Poisson outcome model. If there are no covariates for a certain hidden state, then insert a NULL in the corresponding place in the list. For example, hcovariates = list(~acute + age, ~acute, NULL).

hcovinits

Initial values for the hidden Markov model covariate effects. A list of the same length as hcovariates. Each element is a vector with initial values for the effect of each covariate on that state. For example, the above hcovariates can be initialised with hcovariates = list(c(-8, 0), -8, NULL). Initial values must be given for all or no covariates, if none are given these are all set to zero. The initial value given in the hmodel constructor function for the corresponding baseline parameter is interpreted as the value of that parameter with any covariates fixed to their means in the data. If multiple effects are constrained to be equal using hconstraint, then the initial value is taken from the first of the multiple initial values supplied.

hconstraint

A named list. Each element is a vector of constraints on the named hidden Markov model parameter. The vector has length equal to the number of times that class of parameter appears in the whole model.

For example consider the three-state hidden Markov model described above, with normally-distributed outcomes for states 1 and 2. To constrain the outcome variance to be equal for states 1 and 2, and to also constrain the effect of acute on the outcome mean to be equal for states 1 and 2, specify

hconstraint = list(sd = c(1,1), acute=c(1,1))

Note this excludes initial state occupancy probabilities and covariate effects on those probabilities, which cannot be constrained.

hranges

Range constraints for hidden Markov model parameters. Supplied as a named list, with each element corresponding to the named hidden Markov model parameter. This element is itself a list with two elements, vectors named "lower" and "upper". These vectors each have length equal to the number of times that class of parameter appears in the whole model, and give the corresponding mininum amd maximum allowable values for that parameter. Maximum likelihood estimation is performed with these parameters constrained in these ranges (through a log or logit-type transformation). Lower bounds of -Inf and upper bounds of Inf can be given if the parameter is unbounded above or below.

For example, in the three-state model above, to constrain the mean for state 1 to be between 0 and 6, and the mean of state 2 to be between 7 and 12, supply

hranges=list(mean=list(lower=c(0, 7), upper=c(6, 12)))

These default to the natural ranges, e.g. the positive real line for variance parameters, and [0,1] for probabilities. Therefore hranges need not be specified for such parameters unless an even stricter constraint is desired. If only one limit is supplied for a parameter, only the first occurrence of that parameter is constrained.

Initial values should be strictly within any ranges, and not on the range boundary, otherwise optimisation will fail with a "non-finite value" error.

qconstraint

A vector of indicators specifying which baseline transition intensities are equal. For example,

qconstraint = c(1,2,3,3)

constrains the third and fourth intensities to be equal, in a model with four allowed instantaneous transitions. When there are covariates on the intensities and center=TRUE (the default), qconstraint is applied to the intensities with covariates taking the values of the means in the data. When center=FALSE, qconstraint is applied to the intensities with covariates set to zero.

econstraint

A similar vector of indicators specifying which baseline misclassification probabilities are constrained to be equal. Only used if the model is specified using ematrix, rather than hmodel.

initprobs

Only used in hidden Markov models. Underlying state occupancy probabilities at each subject's first observation. Can either be a vector of nstatesnstates elements with common probabilities to all subjects, or a nsubjectsnsubjects by nstatesnstates matrix of subject-specific probabilities. This refers to observations after missing data and subjects with only one observation have been excluded.

If these are estimated (see est.initprobs), then this represents an initial value, and defaults to equal probability for each state. Otherwise this defaults to c(1, rep(0, nstates-1)), that is, in state 1 with a probability of 1. Scaled to sum to 1 if necessary. The state 1 occupancy probability should be non-zero.

est.initprobs

Only used in hidden Markov models. If TRUE, then the underlying state occupancy probabilities at the first observation will be estimated, starting from a vector of initial values supplied in the initprobs argument. Structural zeroes are allowed: if any of these initial values are zero they will be fixed at zero during optimisation, even if est.initprobs=TRUE, and no covariate effects on them are estimated. The exception is state 1, which should have non-zero occupancy probability.

Note that the free parameters during this estimation exclude the state 1 occupancy probability, which is fixed at one minus the sum of the other probabilities.

initcovariates

Formula representing covariates on the initial state occupancy probabilities, via multinomial logistic regression. The linear effects of these covariates, observed at the individual's first observation time, operate on the log ratio of the state rr occupancy probability to the state 1 occupancy probability, for each r=2r = 2 to the number of states. Thus the state 1 occupancy probability should be non-zero. If est.initprobs is TRUE, these effects are estimated starting from their initial values. If est.initprobs is FALSE, these effects are fixed at theit initial values.

initcovinits

Initial values for the covariate effects initcovariates. A named list with each element corresponding to a covariate, as in covinits. Each element is a vector with (1 - number of states) elements, containing the initial values for the linear effect of that covariate on the log odds of that state relative to state 1, from state 2 to the final state. If initcovinits is not specified, all covariate effects are initialised to zero.

deathexact

Vector of indices of absorbing states whose time of entry is known exactly, but the individual is assumed to be in an unknown transient state ("alive") at the previous instant. This is the usual situation for times of death in chronic disease monitoring data. For example, if you specify deathexact = c(4, 5) then states 4 and 5 are assumed to be exactly-observed death states.

See the obstype argument. States of this kind correspond to obstype=3. deathexact = TRUE indicates that the final absorbing state is of this kind, and deathexact = FALSE or deathexact = NULL (the default) indicates that there is no state of this kind.

The deathexact argument is overridden by obstype or exacttimes.

Note that you do not always supply a deathexact argument, even if there are states that correspond to deaths, because they do not necessarily have obstype=3. If the state is known between the time of death and the previous observation, then you should specify obstype=2 for the death times, or exacttimes=TRUE if the state is known at all times, and the deathexact argument is ignored.

death

Old name for the deathexact argument. Overridden by deathexact if both are supplied. Deprecated.

exacttimes

By default, the transitions of the Markov process are assumed to take place at unknown occasions in between the observation times. If exacttimes is set to TRUE, then the observation times are assumed to represent the exact times of transition of the process. The subject is assumed to be in the same state between these times. An observation may represent a transition to a different state or a repeated observation of the same state (e.g. at the end of follow-up). This is equivalent to every row of the data having obstype = 2. See the obstype argument. If both obstype and exacttimes are specified then exacttimes is ignored.

Note that the complete history of the multi-state process is known with this type of data. The models which msm fits have the strong assumption of constant (or piecewise-constant) transition rates. Knowing the exact transition times allows more realistic models to be fitted with other packages. For example parametric models with sojourn distributions more flexible than the exponential can be fitted with the flexsurv package, or semi-parametric models can be implemented with survival in conjunction with mstate.

censor

A state, or vector of states, which indicates censoring. Censoring means that the observed state is known only to be one of a particular set of states. For example, censor=999 indicates that all observations of 999 in the vector of observed states are censored states. By default, this means that the true state could have been any of the transient (non-absorbing) states. To specify corresponding true states explicitly, use a censor.states argument.

Note that in contrast to the usual terminology of survival analysis, here it is the state which is considered to be censored, rather than the event time. If at the end of a study, an individual has not died, but their true state is known, then censor is unnecessary, since the standard multi-state model likelihood is applicable. Also a "censored" state here can be at any time, not just at the end.

For hidden Markov models, censoring may indicate either a set of possible observed states, or a set of (hidden) true states. The later case is specified by setting the relevant elements of obstrue to 1 (and NA otherwise).

Note in particular that general time-inhomogeneous Markov models with piecewise constant transition intensities can be constructed using the censor facility. If the true state is unknown on occasions when a piecewise constant covariate is known to change, then censored states can be inserted in the data on those occasions. The covariate may represent time itself, in which case the pci option to msm can be used to perform this trick automatically, or some other time-dependent variable.

Not supported for multivariate hidden Markov models specified with hmmMV.

censor.states

Specifies the underlying states which censored observations can represent. If censor is a single number (the default) this can be a vector, or a list with one element. If censor is a vector with more than one element, this should be a list, with each element a vector corresponding to the equivalent element of censor. For example

censor = c(99, 999), censor.states = list(c(2,3), c(3,4))

means that observations coded 99 represent either state 2 or state 3, while observations coded 999 are really either state 3 or state 4.

pci

Model for piecewise-constant intensities. Vector of cut points defining the times, since the start of the process, at which intensities change for all subjects. For example

pci = c(5, 10)

specifies that the intensity changes at time points 5 and 10. This will automatically construct a model with a categorical (factor) covariate called timeperiod, with levels "[-Inf,5)", "[5,10)" and "[10,Inf)", where the first level is the baseline. This covariate defines the time period in which the observation was made. Initial values and constraints on covariate effects are specified the same way as for a model with a covariate of this name, for example,

covinits = list("timeperiod[5,10)"=c(0.1,0.1), "timeperiod[10,Inf)"=c(0.1,0.1))

Thus if pci is supplied, you cannot have a previously-existing variable called timeperiod as a covariate in any part of a msm model.

To assume piecewise constant intensities for some transitions but not others with pci, use the fixedpars argument to fix the appropriate covariate effects at their default initial values of zero.

Internally, this works by inserting censored observations in the data at times when the intensity changes but the state is not observed.

If the supplied times are outside the range of the time variable in the data, pci is ignored and a time-homogeneous model is fitted.

After fitting a time-inhomogeneous model, qmatrix.msm can be used to obtain the fitted intensity matrices for each time period, for example,

qmatrix.msm(example.msm, covariates=list(timeperiod="[5,Inf)"))

This facility does not support interactions between time and other covariates. Such models need to be specified "by hand", using a state variable with censored observations inserted. Note that the data component of the msm object returned from a call to msm with pci supplied contains the states with inserted censored observations and time period indicators. These can be used to construct such models.

Note that you do not need to use pci in order to model the effect of a time-dependent covariate in the data. msm will automatically assume that covariates are piecewise-constant and change at the times when they are observed. pci is for when you want all intensities to change at the same pre-specified times for all subjects.

pci is not supported for multivariate hidden Markov models specified with hmmMV. An approximate equivalent can be constructed by creating a variable in the data to represent the time period, and treating that as a covariate using the covariates argument to msm. This will assume that the value of this variable is constant between observations.

phase.states

Indices of states which have a two-phase sojourn distribution. This defines a semi-Markov model, in which the hazard of an onward transition depends on the time spent in the state.

This uses the technique described by Titman and Sharples (2009). A hidden Markov model is automatically constructed on an expanded state space, where the phases correspond to the hidden states. The "tau" proportionality constraint described in this paper is currently not supported.

Covariates, constraints, deathexact and censor are expressed with respect to the expanded state space. If not supplied by hand, initprobs is defined automatically so that subjects are assumed to begin in the first of the two phases.

Hidden Markov models can additionally be given phased states. The user supplies an outcome distribution for each original state using hmodel, which is expanded internally so that it is assumed to be the same within each of the phased states. initprobs is interpreted on the expanded state space. Misclassification models defined using ematrix are not supported, and these must be defined using hmmCat or hmmIdent constructors, as described in the hmodel section of this help page. Or the HMM on the expanded state space can be defined by hand.

Output functions are presented as it were a hidden Markov model on the expanded state space, for example, transition probabilities between states, covariate effects on transition rates, or prevalence counts, are not aggregated over the hidden phases.

Numerical estimation will be unstable when there is weak evidence for a two-phase sojourn distribution, that is, if the model is close to Markov.

See d2phase for the definition of the two-phase distribution and the interpretation of its parameters.

This is an experimental feature, and some functions are not implemented. Please report any experiences of using this feature to the author!

phase.inits

Initial values for phase-type models. A list with one component for each "two-phased" state. Each component is itself a list of two elements. The first of these elements is a scalar defining the transition intensity from phase 1 to phase 2. The second element is a matrix, with one row for each potential destination state from the two-phased state, and two columns. The first column is the transition rate from phase 1 to the destination state, and the second column is the transition rate from phase 2 to the destination state. If there is only one destination state, then this may be supplied as a vector.

In phase type models, the initial values for transition rates out of non-phased states are taken from the qmatrix supplied to msm, and entries of this matrix corresponding to transitions out of phased states are ignored.

subject.weights

Name of a variable in the data (unquoted) giving weights to apply to each subject in the data when calculating the log-likelihood as a weighted sum over subjects. These are taken from the first observation for each subject, and any weights supplied for subsequent observations are not used.

Weights at the observation level are not supported.

cl

Width of symmetric confidence intervals for maximum likelihood estimates, by default 0.95.

fixedpars

Vector of indices of parameters whose values will be fixed at their initial values during the optimisation. These are given in the order: transition intensities (reading across rows of the transition matrix), covariates on intensities (ordered by intensities within covariates), hidden Markov model parameters, including misclassification probabilities or parameters of HMM outcome distributions (ordered by parameters within states), hidden Markov model covariate parameters (ordered by covariates within parameters within states), initial state occupancy probabilities (excluding the first probability, which is fixed at one minus the sum of the others).

If there are equality constraints on certain parameters, then fixedpars indexes the set of unique parameters, excluding those which are constrained to be equal to previous parameters.

To fix all parameters, specify fixedpars = TRUE.

This can be useful for profiling likelihoods, and building complex models stage by stage.

center

If TRUE (the default, unless fixedpars=TRUE) then covariates are centered at their means during the maximum likelihood estimation. This usually improves stability of the numerical optimisation.

opt.method

If "optim", "nlm" or "bobyqa", then the corresponding R function will be used for maximum likelihood estimation. optim is the default. "bobyqa" requires the package minqa to be installed. See the help of these functions for further details. Advanced users can also add their own optimisation methods, see the source for optim.R in msm for some examples.

If "fisher", then a specialised Fisher scoring method is used (Kalbfleisch and Lawless, 1985) which can be faster than the generic methods, though less robust. This is only available for Markov models with panel data (obstype=1), that is, not for models with censored states, hidden Markov models, exact observation or exact death times (obstype=2,3).

hessian

If TRUE then standard errors and confidence intervals are obtained from a numerical estimate of the Hessian (the observed information matrix). This is the default when maximum likelihood estimation is performed. If all parameters are fixed at their initial values and no optimisation is performed, then this defaults to FALSE. If requested, the actual Hessian is returned in x$paramdata$opt$hessian, where x is the fitted model object.

If hessian is set to FALSE, then standard errors and confidence intervals are obtained from the Fisher (expected) information matrix, if this is available. This may be preferable if the numerical estimation of the Hessian is computationally intensive, or if the resulting estimate is non-invertible or not positive definite.

use.deriv

If TRUE then analytic first derivatives are used in the optimisation of the likelihood, where available and an appropriate quasi-Newton optimisation method, such as BFGS, is being used. Analytic derivatives are not available for all models.

use.expm

If TRUE then any matrix exponentiation needed to calculate the likelihood is done using the expm package. Otherwise the original routines used in msm 1.2.4 and earlier are used. Set to FALSE for backward compatibility, and let the package maintainer know if this gives any substantive differences.

analyticp

By default, the likelihood for certain simpler 3, 4 and 5 state models is calculated using an analytic expression for the transition probability (P) matrix. For all other models, matrix exponentiation is used to obtain P. To revert to the original method of using the matrix exponential for all models, specify analyticp=FALSE. See the PDF manual for a list of the models for which analytic P matrices are implemented.

na.action

What to do with missing data: either na.omit to drop it and carry on, or na.fail to stop with an error. Missing data includes all NAs in the states, times, subject or obstrue, all NAs at the first observation for a subject for covariates in initcovariates, all NAs in other covariates (excluding the last observation for a subject), all NAs in obstype (excluding the first observation for a subject), and any subjects with only one observation (thus no observed transitions).

...

Optional arguments to the general-purpose optimisation routine, optim by default. For example method="Nelder-Mead" to change the optimisation algorithm from the "BFGS" method that msm calls by default.

It is often worthwhile to normalize the optimisation using control=list(fnscale = a), where a is the a number of the order of magnitude of the -2 log likelihood.

If 'false' convergence is reported and the standard errors cannot be calculated due to a non-positive-definite Hessian, then consider tightening the tolerance criteria for convergence. If the optimisation takes a long time, intermediate steps can be printed using the trace argument of the control list. See optim for details.

For the Fisher scoring method, a control list can be supplied in the same way, but the only supported options are reltol, trace and damp. The first two are used in the same way as for optim. If the algorithm fails with a singular information matrix, adjust damp from the default of zero (to, e.g. 1). This adds a constant identity matrix multiplied by damp to the information matrix during optimisation.

Details

For full details about the methodology behind the msm package, refer to the PDF manual ‘msm-manual.pdf’ in the ‘doc’ subdirectory of the package. This includes a tutorial in the typical use of msm. The paper by Jackson (2011) in Journal of Statistical Software presents the material in this manual in a more concise form.

msm was designed for fitting continuous-time Markov models, processes where transitions can occur at any time. These models are defined by intensities, which govern both the time spent in the current state and the probabilities of the next state. In discrete-time models, transitions are known in advance to only occur at multiples of some time unit, and the model is purely governed by the probability distributions of the state at the next time point, conditionally on the state at the current time. These can also be fitted in msm, assuming that there is a continuous-time process underlying the data. Then the fitted transition probability matrix over one time period, as returned by pmatrix.msm(...,t=1) is equivalent to the matrix that governs the discrete-time model. However, these can be fitted more efficiently using multinomial logistic regression, for example, using multinom from the R package nnet (Venables and Ripley, 2002).

For simple continuous-time multi-state Markov models, the likelihood is calculated in terms of the transition intensity matrix QQ. When the data consist of observations of the Markov process at arbitrary times, the exact transition times are not known. Then the likelihood is calculated using the transition probability matrix P(t)=exp(tQ)P(t) = \exp(tQ), where exp\exp is the matrix exponential. If state ii is observed at time tt and state jj is observed at time uu, then the contribution to the likelihood from this pair of observations is the i,ji,j element of P(ut)P(u - t). See, for example, Kalbfleisch and Lawless (1985), Kay (1986), or Gentleman et al. (1994).

For hidden Markov models, the likelihood for an individual with kk observations is calculated directly by summing over the unknown state at each time, producing a product of kk matrices. The calculation is a generalisation of the method described by Satten and Longini (1996), and also by Jackson and Sharples (2002), and Jackson et al. (2003).

There must be enough information in the data on each state to estimate each transition rate, otherwise the likelihood will be flat and the maximum will not be found. It may be appropriate to reduce the number of states in the model, the number of allowed transitions, or the number of covariate effects, to ensure convergence. Hidden Markov models, and situations where the value of the process is only known at a series of snapshots, are particularly susceptible to non-identifiability, especially when combined with a complex transition matrix. Choosing an appropriate set of initial values for the optimisation can also be important. For flat likelihoods, 'informative' initial values will often be required. See the PDF manual for other tips.

Value

To obtain summary information from models fitted by the msm function, it is recommended to use extractor functions such as qmatrix.msm, pmatrix.msm, sojourn.msm, msm.form.qoutput. These provide estimates and confidence intervals for quantities such as transition probabilities for given covariate values.

For advanced use, it may be necessary to directly use information stored in the object returned by msm. This is documented in the help page msm.object.

Printing a msm object by typing the object's name at the command line implicitly invokes print.msm. This formats and prints the important information in the model fit, and also returns that information in an R object. This includes estimates and confidence intervals for the transition intensities and (log) hazard ratios for the corresponding covariates. When there is a hidden Markov model, the chief information in the hmodel component is also formatted and printed. This includes estimates and confidence intervals for each parameter.

Author(s)

C. H. Jackson [email protected]

References

Jackson, C.H. (2011). Multi-State Models for Panel Data: The msm Package for R., Journal of Statistical Software, 38(8), 1-29. URL http://www.jstatsoft.org/v38/i08/.

Kalbfleisch, J., Lawless, J.F., The analysis of panel data under a Markov assumption Journal of the Americal Statistical Association (1985) 80(392): 863–871.

Kay, R. A Markov model for analysing cancer markers and disease states in survival studies. Biometrics (1986) 42: 855–865.

Gentleman, R.C., Lawless, J.F., Lindsey, J.C. and Yan, P. Multi-state Markov models for analysing incomplete disease history data with illustrations for HIV disease. Statistics in Medicine (1994) 13(3): 805–821.

Satten, G.A. and Longini, I.M. Markov chains with measurement error: estimating the 'true' course of a marker of the progression of human immunodeficiency virus disease (with discussion) Applied Statistics 45(3): 275-309 (1996)

Jackson, C.H. and Sharples, L.D. Hidden Markov models for the onset and progression of bronchiolitis obliterans syndrome in lung transplant recipients Statistics in Medicine, 21(1): 113–128 (2002).

Jackson, C.H., Sharples, L.D., Thompson, S.G. and Duffy, S.W. and Couto, E. Multi-state Markov models for disease progression with classification error. The Statistician, 52(2): 193–209 (2003)

Titman, A.C. and Sharples, L.D. Semi-Markov models with phase-type sojourn distributions. Biometrics 66, 742-752 (2009).

Venables, W.N. and Ripley, B.D. (2002) Modern Applied Statistics with S, second edition. Springer.

See Also

simmulti.msm, plot.msm, summary.msm, qmatrix.msm, pmatrix.msm, sojourn.msm.

Examples

### Heart transplant data
### For further details and background to this example, see
### Jackson (2011) or the PDF manual in the doc directory.
print(cav[1:10,])
twoway4.q <- rbind(c(-0.5, 0.25, 0, 0.25), c(0.166, -0.498, 0.166, 0.166),
c(0, 0.25, -0.5, 0.25), c(0, 0, 0, 0))
statetable.msm(state, PTNUM, data=cav)
crudeinits.msm(state ~ years, PTNUM, data=cav, qmatrix=twoway4.q)
cav.msm <- msm( state ~ years, subject=PTNUM, data = cav,
                 qmatrix = twoway4.q, deathexact = 4, 
                 control = list ( trace = 2, REPORT = 1 )  )
cav.msm
qmatrix.msm(cav.msm)
pmatrix.msm(cav.msm, t=10)
sojourn.msm(cav.msm)

Extract msm model parameter estimates in compact format

Description

Extract estimates and confidence intervals for transition intensities (or misclassification probabilities), and their covariate effects, in a tidy matrix format with one row per transition. This is used by the print method (print.msm) for msm objects. Covariate effects are returned as hazard or odds ratios, not on the log scale.

Usage

msm.form.qoutput(x, covariates = "mean", cl = 0.95, digits = 4, ...)

msm.form.eoutput(x, covariates = "mean", cl = 0.95, digits = 4, ...)

Arguments

x

A fitted multi-state model object, as returned by msm.

covariates

Covariate values defining the "baseline" parameters (see qmatrix.msm).

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

digits

Minimum number of significant digits for the formatted character matrix returned as an attribute. This is passed to format. Defaults to 4.

...

Other arguments to be passed to format.

Value

A numeric matrix with one row per transition, and one column for each estimate or confidence limit. The "formatted" attribute contains the same results formatted for pretty printing. msm.form.qoutput returns the transition intensities and their covariates, and msm.form.eoutput returns the misclassification probabilities and their covariates.

Author(s)

C. H. Jackson [email protected]

See Also

print.msm


Fitted msm model objects

Description

The msm function returns a list with the following components. These are intended for developers and confident users. To extract results from fitted model objects, functions such as qmatrix.msm or print.msm should be used instead.

Value

call

The original call to msm, as returned by match.call.

Qmatrices

A list of matrices. The first component, labelled logbaseline, is a matrix containing the estimated transition intensities on the log scale with any covariates fixed at their means in the data (or at zero, if center=FALSE). The component labelled baseline is the equivalent on the untransformed scale. Each remaining component is a matrix giving the linear effects of the labelled covariate on the matrix of log intensities. To extract an estimated intensity matrix on the natural scale, at an arbitrary combination of covariate values, use the function qmatrix.msm.

QmatricesSE

The standard error matrices corresponding to Qmatrices.

QmatricesL, QmatricesU

Corresponding lower and upper symmetric confidence limits, of width 0.95 unless specified otherwise by the cl argument.

Ematrices

A list of matrices. The first component, labelled logitbaseline, is the estimated misclassification probability matrix (expressed as as log odds relative to the probability of the true state) with any covariates fixed at their means in the data (or at zero, if center=FALSE). The component labelled baseline is the equivalent on the untransformed scale. Each remaining component is a matrix giving the linear effects of the labelled covariate on the matrix of logit misclassification probabilities. To extract an estimated misclassification probability matrix on the natural scale, at an arbitrary combination of covariate values, use the function ematrix.msm.

EmatricesSE

The standard error matrices corresponding to Ematrices.

EmatricesL, EmatricesU

Corresponding lower and upper symmetric confidence limits, of width 0.95 unless specified otherwise by the cl argument.

minus2loglik

Minus twice the maximised log-likelihood.

deriv

Derivatives of the minus twice log-likelihood at its maximum.

estimates

Vector of untransformed maximum likelihood estimates returned from optim. Transition intensities are on the log scale and misclassification probabilities are given as log odds relative to the probability of the true state.

estimates.t

Vector of transformed maximum likelihood estimates with intensities and probabilities on their natural scales.

fixedpars

Indices of estimates which were fixed during the maximum likelihood estimation.

center

Indicator for whether the estimation was performed with covariates centered on their means in the data.

covmat

Covariance matrix corresponding to estimates.

ci

Matrix of confidence intervals corresponding to estimates.t

opt

Return value from the optimisation routine (such as optim or nlm), giving information about the results of the optimisation.

foundse

Logical value indicating whether the Hessian was positive-definite at the supposed maximum of the likelihood. If not, the covariance matrix of the parameters is unavailable. In these cases the optimisation has probably not converged to a maximum.

data

A list giving the data used for the model fit, for use in post-processing. To extract it, use the methods model.frame.msm or model.matrix.msm.

The format of this element changed in version 1.4 of msm, so that it now contains a model.frame object mf with all the variables used in the model. The previous format (an ad-hoc list of vectors and matrices) can be obtained with the function recreate.olddata(msmobject), where msmobject is the object returned by msm.

qmodel

A list of objects representing the transition matrix structure and options for likelihood calculation. See qmodel.object for documentation of the components.

emodel

A list of objects representing the misclassification model structure, for models specified using the ematrix argument to msm. See emodel.object.

qcmodel

A list of objects representing the model for covariates on transition intensities. See qcmodel.object.

ecmodel

A list of objects representing the model for covariates on transition intensities. See ecmodel.object.

hmodel

A list of objects representing the hidden Markov model structure. See hmodel.object.

cmodel

A list giving information about censored states. See cmodel.object.

pci

Cut points for time-varying intensities, as supplied to msm, but excluding any that are outside the times observed in the data.

paramdata

A list giving information about the parameters of the multi-state model. See paramdata.object.

cl

Confidence interval width, as supplied to msm.

covariates

Formula for covariates on intensities, as supplied to msm.

misccovariates

Formula for covariates on misclassification probabilities, as supplied to msm.

hcovariates

Formula for covariates on hidden Markov model outcomes, as supplied to msm.

initcovariates

Formula for covariates on initial state occupancy probabilities in hidden Markov models, as supplied to msm.

sojourn

A list as returned by sojourn.msm, with components:

mean = estimated mean sojourn times in the transient states, with covariates fixed at their means (if center=TRUE) or at zero (if center=FALSE).

se = corresponding standard errors.


Convert data for ‘msm’ to data for ‘survival’, ‘mstate’ or ‘flexsurv’ analysis

Description

Converts longitudinal data for a msm model fit, where observations represent the exact transition times of the process, to counting process data. This enables, for example, flexible parametric multi-state models to be fitted with flexsurvreg from the flexsurv package, or semiparametric models to be implemented with coxph and the mstate package.

Usage

msm2Surv(data, subject, time, state, covs = NULL, Q)

Arguments

data

Data frame in the format expected by a msm model fit with exacttimes=TRUE or all obstype=2. Each row represents an observation of a state, and the time variable contains the exact and complete transition times of the underlying process. This is explained in more detail in the help page for msm, section obstype=2.

subject

Name of the subject ID in the data (character format, i.e. quoted).

time

Name of the time variable in the data (character).

state

Name of the state variable in the data (character).

covs

Vector of covariate names to carry through (character). If not supplied, this is taken to be all remaining variables in the data.

Q

Transition intensity matrix. This should have number of rows and number of columns both equal to the number of states. If an instantaneous transition is not allowed from state rr to state ss, then Q should have (r,s)(r,s) entry 0, otherwise it should be non-zero. The diagonal entries are ignored.

Details

For example, if the data supplied to msm look like this:

subj days status age treat
1 0 1 66 1
1 27 2 66 1
1 75 3 66 1
1 97 4 66 1
1 1106 4 69 1
2 0 1 49 0
2 90 2 49 0
2 1037 2 51 0

then the output of msm2Surv will be a data frame looking like this:

id from to Tstart Tstop time status age treat trans
1 1 2 0 27 27 1 66 1 1
1 1 4 0 27 27 0 66 1 2
1 2 3 27 75 48 1 66 1 3
1 2 4 27 75 48 0 66 1 4
1 3 4 75 97 22 1 69 1 5
2 1 2 0 90 90 1 49 0 1
2 1 4 0 90 90 0 49 0 2
2 2 3 90 1037 947 0 49 0 3
2 2 4 90 1037 947 0 49 0 4

At 27 days, subject 1 is observed to move from state 1 to state 2 (first row, status 1), which means that their potential transition from state 1 to state 4 is censored (second row, status 0).

See the mstate package and the references below for more details of this data format and using it for semi-parametric multi-state modelling.

Value

A data frame of class "msdata", with rows representing observed or censored transitions. There will be one row for each observed transition in the original data, and additional rows for every potential transition that could have occurred out of each observed state.

The data frame will have columns called:

id

Subject ID

from

Starting state of the transition

to

Finishing state of the transition

Tstart

The starting time of the transition

Tstop

The finishing time of the transition

time

The time difference = Tstop - Tstart

status

Event or censoring indicator, with 1 indicating an observed transition, and 0 indicating censoring

trans

Transition number

and any remaining columns will represent covariates. Any covariates whose names clash with the standard variables in the returned data ("id", "from", "to", "Tstart", "Tstop", "time", "status" or "trans") have ".2" appended to their names.

The transition matrix in mstate format is stored in the trans attribute of the returned object. See the example code below.

Author(s)

C. H. Jackson [email protected]

References

Putter H, Fiocco M, Geskus RB (2007). Tutorial in biostatistics: Competing risks and multi-state models. Statistics in Medicine 26: 2389-2430.

Liesbeth C. de Wreede, Marta Fiocco, Hein Putter (2011). mstate: An R Package for the Analysis of Competing Risks and Multi-State Models. Journal of Statistical Software, 38(7), 1-30.

Jackson, C. H. (2014). flexsurv: Flexible parametric survival and multi-state models. R package version 0.5.

See Also

msprep, in mstate, which produces data in a similar format, given data in "wide" format with one row per subject.

Examples

msmdat <- data.frame(
 subj = c(1, 1, 1, 1, 1, 2, 2, 2),
 days = c(0, 27, 75, 97, 1106, 0, 90, 1037),
 status = c(1, 2, 3, 4, 4, 1, 2, 2),
 age = c(66, 66, 66, 66, 69, 49, 49, 51),
 treat = c(1, 1, 1, 1, 1, 0, 0, 0)
)
# transitions only allowed to next state up or state 4
Q <- rbind(c(1, 1, 0, 1), 
           c(0, 1, 1, 1),
           c(0, 0, 1, 1),
           c(0, 0, 0, 0))
dat <- msm2Surv(data=msmdat, subject="subj", time="days", state="status", 
         Q=Q)
dat
attr(dat, "trans")

Calculate tables of odds ratios for covariates on misclassification probabilities

Description

Odds ratios are computed by exponentiating the estimated covariate effects on the logit-misclassification probabilities.

Usage

odds.msm(x, odds.scale = 1, cl = 0.95)

Arguments

x

Output from msm representing a fitted multi-state model.

odds.scale

Vector with same elements as number of covariates on misclassification probabilities. Corresponds to the increase in each covariate used to calculate its odds ratio. Defaults to all 1.

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

Value

A list of tables containing odds ratio estimates, one table for each covariate. Each table has three columns, containing the odds ratio, and an approximate upper 95% and lower 95% confidence limit respectively (assuming normality on the log scale), for each misclassification probability.

Author(s)

C. H. Jackson [email protected]

See Also

msm, hazard.msm


Developer documentation: internal msm parameters object

Description

An object giving information about the parameters of the multi-state model. Used internally during maximum likelihood estimation and arranging results. Returned as the paramdata component of a fitted msm model object.

Value

inits

Vector of initial values for distinct parameters which are being estimated. These have been transformed to the real line (e.g. by log), and exclude parameters being fixed at their initial values, parameters defined to be always fixed (e.g. binomial denominators) and parameters constrained to equal previous ones.

plabs

Names of parameters in allinits.

allinits

Vector of parameter values before estimation, including those which are fixed or constrained to equal other parameters, and transformed to the real line.

hmmpars

Indices of allinits which represent baseline parameters of hidden Markov outcome models (thus excluding covariate effects in HMMs and initial state occupancy probabilities).

fixed

TRUE if all parameters are fixed, FALSE otherwise.

fixedpars

Indices of parameters in allinits which are fixed, either by definition or as requested by the user in the fixedpars argument to msm. Excludes parameters fixed by constraining to equal other parameters.

notfixed

Indices of parameters which are not fixed by the definition of fixedpars.

optpars

Indices of parameters in allinits being estimated, thus those included in inits.

auxpars

Indices of "auxiliary" parameters which are always fixed, for example, binomial denominators (hmmBinom) and the which parameter in hmmIdent.

constr

Vector of integers, of length npars, indicating which sets of parameters are constrained to be equal to each other. If two of these integers are equal the corresponding parameters are equal. A negative element indicates that parameter is defined to be minus some other parameter (this is used for covariate effects on transition intensities).

npars

Total number of parameters, equal to length(allinits).

nfix

Number of fixed parameters, equal to length(fixedpars).

nopt

Number of parameters being estimated, equal to length(inits) and length(optpars).

ndup

Number of parameters defined as duplicates of previous parameters by equality constraints (currently unused).

ranges

Matrix of defined ranges for each parameter on the natural scale (e.g. 0 to infinity for rate parameters).

opt

Object returned by the optimisation routine (such as optim).

foundse

TRUE if standard errors are available after optimisation. If FALSE the optimisation probably hasn't converged.

lik

Minus twice the log likelihood at the parameter estimates.

deriv

Derivatives of the minus twice log likelihood at the parameter estimates, if available.

information

Corresponding expected information matrix at the parameter estimates, if available.

params

Vector of parameter values after maximum likelihood estimation, corresponding to allinits, still on the real-line transformed scale.

covmat

Covariance matrix corresponding to params.

ci

Matrix of confidence intervals corresponding to params, with nominal coverage (default 0.95) defined by the cl argument of msm.

estimates.t

Vector of parameter estimates, as params but with parameters on their natural scales.

See Also

msm.object


Pearson-type goodness-of-fit test

Description

Pearson-type goodness-of-fit test for multi-state models fitted to panel-observed data.

Usage

pearson.msm(
  x,
  transitions = NULL,
  timegroups = 3,
  intervalgroups = 3,
  covgroups = 3,
  groups = NULL,
  boot = FALSE,
  B = 500,
  next.obstime = NULL,
  N = 100,
  indep.cens = TRUE,
  maxtimes = NULL,
  pval = TRUE
)

Arguments

x

A fitted multi-state model, as returned by msm.

transitions

This should be an integer vector indicating which interval transitions should be grouped together in the contingency table. Its length should be the number of allowed interval transitions, excluding transitions from absorbing states to absorbing states.

The allowed interval transitions are the set of pairs of states (a,b)(a,b) for which it is possible to observe aa at one time and bb at any later time. For example, in a "well-disease-death" model with allowed instantaneous 1-2, 2-3 transitions, there are 5 allowed interval transitions. In numerical order, these are 1-1, 1-2, 1-3, 2-2 and 2-3, excluding absorbing-absorbing transitions.

Then, to group transitions 1-1,1-2 together, and transitions 2-2,2-3 together, specify

transitions = c(1,1,2,3,3).

Only transitions from the same state may be grouped. By default, each interval transition forms a separate group.

timegroups

Number of groups based on quantiles of the time since the start of the process.

intervalgroups

Number of groups based on quantiles of the time interval between observations, within time groups

covgroups

Number of groups based on quantiles of rqirr\sum_r q_{irr}, where qirrq_{irr} are the diagonal entries of the transition intensity matrix for the ith transition. These are a function of the covariate effects and the covariate values at the ith transition: qirrq_{irr} is minus the sum of the off-diagonal entries qrs(0)exp(βrsTzi)q_{rs}^{(0)} exp (\beta_{rs}^T z_i) on the rth row.

Thus covgroups summarises the impact of covariates at each observation, by calculating the overall rate of progression through states at that observation.

For time-inhomogeneous models specified using the pci argument to msm, if the only covariate is the time period, covgroups is set to 1, since timegroups ensures that transitions are grouped by time.

groups

A vector of arbitrary groups in which to categorise each transition. This can be an integer vector or a factor. This can be used to diagnose specific areas of poor fit. For example, the contingency table might be grouped by arbitrary combinations of covariates to detect types of individual for whom the model fits poorly.

The length of groups should be x$data$n, the number of observations used in the model fit, which is the number of observations in the original dataset with any missing values excluded. The value of groups at observation ii is used to categorise the transition which ends at observation i. Values of groups at the first observation for each subject are ignored.

boot

Estimate an "exact" p-value using a parametric bootstrap.

All objects used in the original call to msm which produced x, such as the qmatrix, should be in the working environment, or else an “object not found” error will be given. This enables the original model to be refitted to the replicate datasets.

Note that groups cannot be used with bootstrapping, as the simulated observations will not be in the same categories as the original observations.

B

Number of bootstrap replicates.

next.obstime

This is a vector of length x$data$n (the number of observations used in the model fit) giving the time to the next scheduled observation following each time point. This is only used when times to death are known exactly.

For individuals who died (entered an absorbing state) before the next scheduled observation, and the time of death is known exactly, next.obstime would be greater than the observed death time.

If the individual did not die, and a scheduled observation did follow that time point, next.obstime should just be the same as the time to that observation.

next.obstime is used to determine a grouping of the time interval between observations, which should be based on scheduled observations. If exact times to death were used in the grouping, then shorter intervals would contain excess deaths, and the goodness-of-fit statistic would be biased.

If next.obstime is unknown, it is multiply-imputed using a product-limit estimate based on the intervals to observations other than deaths. The resulting tables of transitions are averaged over these imputations. This may be slow.

N

Number of imputations for the estimation of the distribution of the next scheduled observation time, when there are exact death times.

indep.cens

If TRUE, then times to censoring are included in the estimation of the distribution to the next scheduled observation time. If FALSE, times to censoring are assumed to be systematically different from other observation times.

maxtimes

A vector of length x$data$n, or a common scalar, giving an upper bound for the next scheduled observation time. Used in the multiple imputation when times to death are known exactly. If a value greater than maxtimes is simulated, then the next scheduled observation is taken as censored. This should be supplied, if known. If not supplied, this is taken to be the maximum interval occurring in the data, plus one time unit. For observations which are not exact death times, this should be the time since the previous observation.

pval

Calculate a p-value using the improved approximation of Titman (2009). This is optional since it is not needed during bootstrapping, and it is computationally non-trivial. Only available currently for non-hidden Markov models for panel data without exact death times. Also not available for models with censoring, including time-homogeneous models fitted with the pci option to msm.

Details

This method (Aguirre-Hernandez and Farewell, 2002) is intended for data which represent observations of the process at arbitrary times ("snapshots", or "panel-observed" data). For data which represent the exact transition times of the process, prevalence.msm can be used to assess fit, though without a formal test.

When times of death are known exactly, states are misclassified, or an individual's final observation is a censored state, the modification by Titman and Sharples (2008) is used. The only form of censoring supported is a state at the end of an individual's series which represents an unknown transient state (i.e. the individual is only known to be alive at this time). Other types of censoring are omitted from the data before performing the test.

See the references for further details of the methods. The method used for censored states is a modification of the method in the appendix to Titman and Sharples (2008), described at https://chjackson.github.io/msm/misc/robustcensoring.pdf (Titman, 2007).

Groupings of the time since initiation, the time interval and the impact of covariates are based on equally-spaced quantiles. The number of groups should be chosen that there are not many cells with small expected numbers of transitions, since the deviance statistic will be unstable for sparse contingency tables. Ideally, the expected numbers of transitions in each cell of the table should be no less than about 5. Conversely, the power of the test is reduced if there are too few groups. Therefore, some sensitivity analysis of the test results to the grouping is advisable.

Saved model objects fitted with previous versions of R (versions less than 1.2) will need to be refitted under the current R for use with pearson.msm.

Value

A list whose first two elements are contingency tables of observed transitions OO and expected transitions EE, respectively, for each combination of groups. The third element is a table of the deviances (OE)2/E(O - E)^2 / E multiplied by the sign of OEO - E. If the expected number of transitions is zero then the deviance is zero. Entries in the third matrix will be bigger in magnitude for groups for which the model fits poorly.

list("\"test\"")

the fourth element of the list, is a data frame with one row containing the Pearson-type goodness-of-fit test statistic stat. The test statistic is the sum of the deviances. For panel-observed data without exact death times, misclassification or censored observations, p is the p-value for the test statistic calculated using the improved approximation of Titman (2009).

For these models, for comparison with older versions of the package, test also presents p.lower and p.upper, which are theoretical lower and upper limits for the p-value of the test statistic, based on chi-squared distributions with df.lower and df.upper degrees of freedom, respectively. df.upper is the number of independent cells in the contingency table, and df.lower is df.upper minus the number of estimated parameters in the model.

list("\"intervalq\"")

(not printed by default) contains the definition of the grouping of the intervals between observations. These groups are defined by quantiles within the groups corresponding to the time since the start of the process.

list("\"sim\"")

If there are exact death times, this contains simulations of the contingency tables and test statistics for each imputation of the next scheduled sampling time. These are averaged over to produce the presented tables and test statistic. This element is not printed by default.

With exact death times, the null variance of the test statistic (formed by taking mean of simulated test statistics) is less than twice the mean (Titman, 2008), and the null distribution is not chi-squared. In this case, p.upper is an upper limit for the true asymptotic p-value, but p.lower is not a lower limit, and is not presented.

list("\"boot\"")

If the bootstrap has been used, the element will contain the bootstrap replicates of the test statistics (not printed by default).

list("\"lambda\"")

If the Titman (2009) p-value has been calculated, this contains the weights defining the null distribution of the test statistic as a weighted sum of chi-squared(1) random variables (not printed by default).

Author(s)

Andrew Titman [email protected], Chris Jackson [email protected]

References

Aguirre-Hernandez, R. and Farewell, V. (2002) A Pearson-type goodness-of-fit test for stationary and time-continuous Markov regression models. Statistics in Medicine 21:1899-1911.

Titman, A. and Sharples, L. (2008) A general goodness-of-fit test for Markov and hidden Markov models. Statistics in Medicine 27(12):2177-2195

Titman, A. (2009) Computation of the asymptotic null distribution of goodness-of-fit tests for multi-state models. Lifetime Data Analysis 15(4):519-533.

Titman, A. (2008) Model diagnostics in multi-state models of biological systems. PhD thesis, University of Cambridge.

See Also

msm, prevalence.msm, scoreresid.msm,

Examples

psor.q <- rbind(c(0,0.1,0,0),c(0,0,0.1,0),c(0,0,0,0.1),c(0,0,0,0))
psor.msm <- msm(state ~ months, subject=ptnum, data=psor,
                qmatrix = psor.q, covariates = ~ollwsdrt+hieffusn,
                constraint = list(hieffusn=c(1,1,1),ollwsdrt=c(1,1,2)))
pearson.msm(psor.msm, timegroups=2, intervalgroups=2, covgroups=2)
# More 1-2, 1-3 and 1-4 observations than expected in shorter time
# intervals - the model fits poorly.
# A random effects model might accommodate such fast progressors.

Exponential distribution with piecewise-constant rate

Description

Density, distribution function, quantile function and random generation for a generalisation of the exponential distribution, in which the rate changes at a series of times.

Usage

dpexp(x, rate = 1, t = 0, log = FALSE)

ppexp(q, rate = 1, t = 0, lower.tail = TRUE, log.p = FALSE)

qpexp(p, rate = 1, t = 0, lower.tail = TRUE, log.p = FALSE)

rpexp(n = 1, rate = 1, t = 0, start = min(t))

Arguments

x, q

vector of quantiles.

rate

vector of rates.

t

vector of the same length as rate, giving the times at which the rate changes. The values of t should be in increasing order.

log, log.p

logical; if TRUE, probabilities p are given as log(p), or log density is returned.

lower.tail

logical; if TRUE (default), probabilities are P[X <= x], otherwise, P[X > x].

p

vector of probabilities.

n

number of observations. If length(n) > 1, the length is taken to be the number required.

start

numeric scalar; delayed entry time. The random deviates will be left truncated from this start time.

Details

Consider the exponential distribution with rates r1,,r_1, \ldots,rnr_n changing at times t1,,tnt_1, \ldots, t_n, with t1=0t_1 = 0. Suppose tkt_k is the maximum tit_i such that ti<xt_i < x. The density of this distribution at x>0x > 0 is f(x)f(x) for k=1k = 1, and

i=1k(1F(titi1,ri))f(xtk,rk)\prod_{i=1}^k (1 - F(t_{i} - t_{i-1}, r_i)) f(x - t_{k}, r_{k})

for k > 1.

where F()F() and f()f() are the distribution and density functions of the standard exponential distribution.

If rate is of length 1, this is just the standard exponential distribution. Therefore, for example, dpexp(x), with no other arguments, is simply equivalent to dexp(x).

Only rpexp is used in the msm package, to simulate from Markov processes with piecewise-constant intensities depending on time-dependent covariates. These functions are merely provided for completion, and are not optimized for numerical stability or speed.

Value

dpexp gives the density, ppexp gives the distribution function, qpexp gives the quantile function, and rpexp generates random deviates.

Author(s)

C. H. Jackson [email protected]

See Also

dexp, sim.msm.

Examples

x <- seq(0.1, 50, by=0.1)
rate <- c(0.1, 0.2, 0.05, 0.3)
t <- c(0, 10, 20, 30)
## standard exponential distribution
plot(x, dexp(x, 0.1), type="l")
## distribution with piecewise constant rate
lines(x, dpexp(x, rate, t), type="l", lty=2)
## standard exponential distribution
plot(x, pexp(x, 0.1), type="l")
## distribution with piecewise constant rate
lines(x, ppexp(x, rate, t), type="l", lty=2)

Parameters of phase-type models in mixture form

Description

Parameters of fitted two-phase models, in mixture model parameterisation.

Usage

phasemeans.msm(
  x,
  covariates = "mean",
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL
)

Arguments

x

A fitted multi-state model, as returned by msm.

covariates

Covariate values, see qmatrix.msm.

ci

If "none" (the default) no confidence intervals are calculated. Otherwise "normal", or "boot" as described by qmatrix.msm.

cl

Width of the symmetric confidence interval, relative to 1.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs.

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

Value

Matrix with one row for each state that has a two-phase distribution, and three columns: the short-stay mean, long-stay mean and long-stay probability. These are functions of the transition intensities of the expanded hidden Markov model, defined in d2phase.

Author(s)

C. H. Jackson [email protected]

See Also

d2phase.


Plots of multi-state models

Description

This produces a plot of the expected probability of survival against time, from each transient state. Survival is defined as not entering an absorbing state.

Usage

## S3 method for class 'msm'
plot(
  x,
  from = NULL,
  to = NULL,
  range = NULL,
  covariates = "mean",
  legend.pos = NULL,
  xlab = "Time",
  ylab = "Fitted survival probability",
  lwd = 1,
  ...
)

Arguments

x

Output from msm, representing a fitted multi-state model object.

from

States from which to consider survival. Defaults to the complete set of transient states.

to

Absorbing state to consider. Defaults to the highest-labelled absorbing state.

range

Vector of two elements, giving the range of times to plot for.

covariates

Covariate values for which to evaluate the expected probabilities. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula, or a named list,

list (age = 60, sex = 1)

legend.pos

Vector of the xx and yy position, respectively, of the legend.

xlab

x axis label.

ylab

y axis label.

lwd

Line width. See par.

...

Other arguments to be passed to the generic plot and lines functions.

Details

Note that while this function is only relevant to models with absorbing states, models in msm can have any transition structure and do not necessarily have to have an absorbing state.

Author(s)

C. H. Jackson [email protected]

See Also

msm


Plot of observed and expected prevalences

Description

Provides a rough indication of goodness of fit of a multi-state model, by estimating the observed numbers of individuals occupying a state at a series of times, and plotting these against forecasts from the fitted model, for each state. Observed prevalences are indicated as solid lines, expected prevalences as dashed lines.

Usage

## S3 method for class 'prevalence.msm'
plot(
  x,
  mintime = NULL,
  maxtime = NULL,
  timezero = NULL,
  initstates = NULL,
  interp = c("start", "midpoint"),
  censtime = Inf,
  subset = NULL,
  covariates = "population",
  misccovariates = "mean",
  piecewise.times = NULL,
  piecewise.covariates = NULL,
  xlab = "Times",
  ylab = "Prevalence (%)",
  lwd.obs = 1,
  lwd.exp = 1,
  lty.obs = 1,
  lty.exp = 2,
  col.obs = "blue",
  col.exp = "red",
  legend.pos = NULL,
  ...
)

Arguments

x

A fitted multi-state model produced by msm.

mintime

Minimum time at which to compute the observed and expected prevalences of states.

maxtime

Maximum time at which to compute the observed and expected prevalences of states.

timezero

Initial time of the Markov process. Expected values are forecasted from here. Defaults to the minimum of the observation times given in the data.

initstates

Optional vector of the same length as the number of states. Gives the numbers of individuals occupying each state at the initial time, to be used for forecasting expected prevalences. The default is those observed in the data. These should add up to the actual number of people in the study at the start.

interp

Interpolation method for observed states, see prevalence.msm.

censtime

Subject-specific maximum follow-up times, see prevalence.msm.

subset

Vector of the subject identifiers to calculated observed prevalences for.

covariates

Covariate values for which to forecast expected state occupancy. See prevalence.msm — if this function runs too slowly, as it may if there are continuous covariates, replace covariates="population" with covariates="mean".

misccovariates

(Misclassification models only) Values of covariates on the misclassification probability matrix. See prevalence.msm.

piecewise.times

Times at which piecewise-constant intensities change. See prevalence.msm.

piecewise.covariates

Covariates on which the piecewise-constant intensities depend. See prevalence.msm.

xlab

x axis label.

ylab

y axis label.

lwd.obs

Line width for observed prevalences. See par.

lwd.exp

Line width for expected prevalences. See par.

lty.obs

Line type for observed prevalences. See par.

lty.exp

Line type for expected prevalences. See par.

col.obs

Line colour for observed prevalences. See par.

col.exp

Line colour for expected prevalences. See par.

legend.pos

Vector of the xx and yy position, respectively, of the legend.

...

Further arguments to be passed to the generic plot function.

Details

See prevalence.msm for details of the assumptions underlying this method.

Observed prevalences are plotted with a solid line, and expected prevalences with a dotted line.

References

Gentleman, R.C., Lawless, J.F., Lindsey, J.C. and Yan, P. Multi-state Markov models for analysing incomplete disease history data with illustrations for HIV disease. Statistics in Medicine (1994) 13(3): 805–821.

See Also

prevalence.msm


Plot empirical and fitted survival curves

Description

Plot a Kaplan-Meier estimate of the survival probability and compare it with the fitted survival probability from a msm model.

Usage

## S3 method for class 'survfit.msm'
plot(
  x,
  from = 1,
  to = NULL,
  range = NULL,
  covariates = "mean",
  interp = c("start", "midpoint"),
  ci = c("none", "normal", "bootstrap"),
  B = 100,
  legend.pos = NULL,
  xlab = "Time",
  ylab = "Survival probability",
  lty = 1,
  lwd = 1,
  col = "red",
  lty.ci = 2,
  lwd.ci = 1,
  col.ci = "red",
  mark.time = TRUE,
  col.surv = "blue",
  lty.surv = 2,
  lwd.surv = 1,
  survdata = FALSE,
  ...
)

Arguments

x

Output from msm, representing a fitted multi-state model object.

from

Non-absorbing state from which to consider survival. Defaults to state 1. The fitted probabilities will then be calculated as the transition probabilities from this state to to. The empirical survival curve plots survival from the first observation of from (where this exists) to the first entry time into to.

to

Absorbing state to consider. Defaults to the highest-labelled absorbing state.

range

Vector of two elements, giving the range of times to plot for.

covariates

Covariate values for which to evaluate the expected probabilities. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula, or a named list,

list (age = 60, sex = 1)

but note the empirical curve is plotted for the full population. To consider subsets for the empirical curve, set survdata=TRUE to extract the survival data and build a survival plot by hand using plot.survfit.

interp

If interp="start" (the default) then the entry time into the absorbing state is assumed to be the time it is first observed in the data.

If interp="midpoint" then the entry time into the absorbing state is assumed to be halfway between the time it is first observed and the previous observation time. This is generally more reasonable for "progressive" models with observations at arbitrary times.

ci

If "none" (the default) no confidence intervals are plotted. If "normal" or "bootstrap", confidence intervals are plotted based on the respective method in pmatrix.msm. This is very computationally-intensive, since intervals must be computed at a series of times.

B

Number of bootstrap or normal replicates for the confidence interval. The default is 100 rather than the usual 1000, since these plots are for rough diagnostic purposes.

legend.pos

Vector of the xx and yy position, respectively, of the legend.

xlab

x axis label.

ylab

y axis label.

lty

Line type for the fitted curve. See par.

lwd

Line width for the fitted curve. See par.

col

Colour for the fitted curve. See par.

lty.ci

Line type for the fitted curve confidence limits. See par.

lwd.ci

Line width for the fitted curve confidence limits. See par.

col.ci

Colour for the fitted curve confidence limits. See par.

mark.time

Mark the empirical survival curve at each censoring point, see lines.survfit.

col.surv

Colour for the empirical survival curve, passed to lines.survfit. See par.

lty.surv

Line type for the empirical survival curve, passed to lines.survfit. See par.

lwd.surv

Line width for the empirical survival curve, passed to lines.survfit. See par.

survdata

Set to TRUE to return the survival data frame constructed when plotting the empirical curve. This can be used for constructing survival plots by hand using plot.survfit.

...

Other arguments to be passed to the plot function which draws the fitted curve, or the lines.survfit function which draws the empirical curve.

Details

If the data represent observations of the process at arbitrary times, then the first occurrence of the absorbing state in the data will usually be greater than the actual first transition time to that state. Therefore the Kaplan-Meier estimate of the survival probability will be an overestimate.

The method of Turnbull (1976) could be used to give a non-parametric estimate of the time to an interval-censored event, and compared to the equivalent estimate from a multi-state model. This is implemented in the CRAN package interval (Fay and Shaw 2010).

This currently only handles time-homogeneous models.

References

Turnbull, B. W. (1976) The empirical distribution function with arbitrarily grouped, censored and truncated data. J. R. Statist. Soc. B 38, 290-295.

Fay, MP and Shaw, PA (2010). Exact and Asymptotic Weighted Logrank Tests for Interval Censored Data: The interval R package. Journal of Statistical Software. http://www.jstatsoft.org/v36/ i02/. 36 (2):1-34.

See Also

survfit, plot.survfit, plot.prevalence.msm


Kaplan Meier estimates of incidence

Description

Compute and plot Kaplan-Meier estimates of the probability that each successive state has not occurred yet.

Usage

plotprog.msm(
  formula,
  subject,
  data,
  legend.pos = NULL,
  xlab = "Time",
  ylab = "1 - incidence probability",
  lwd = 1,
  xlim = NULL,
  mark.time = TRUE,
  ...
)

Arguments

formula

A formula giving the vectors containing the observed states and the corresponding observation times. For example,

state ~ time

Observed states should be in the set 1, ...{}, n, where n is the number of states.

subject

Vector of subject identification numbers for the data specified by formula. If missing, then all observations are assumed to be on the same subject. These must be sorted so that all observations on the same subject are adjacent.

data

An optional data frame in which the variables represented by state, time and subject can be found.

legend.pos

Vector of the xx and yy position, respectively, of the legend.

xlab

x axis label.

ylab

y axis label.

lwd

Line width. See par.

xlim

x axis limits, e.g. c(0,10) for an axis ranging from 0 to 10. Default is the range of observation times.

mark.time

Mark the empirical survival curve at each censoring point, see lines.survfit.

...

Other arguments to be passed to the plot and lines.survfit functions.

Details

If the data represent observations of the process at arbitrary times, then the first occurrence of the state in the data will usually be greater than the actual first transition time to that state. Therefore the probabilities plotted by plotprog.msm will be overestimates.

See Also

survfit, plot.survfit


Transition probability matrix

Description

Extract the estimated transition probability matrix from a fitted continuous-time multi-state model for a given time interval, at a given set of covariate values.

Usage

pmatrix.msm(
  x = NULL,
  t = 1,
  t1 = 0,
  covariates = "mean",
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL,
  qmatrix = NULL,
  ...
)

Arguments

x

A fitted multi-state model, as returned by msm.

t

The time interval to estimate the transition probabilities for, by default one unit.

t1

The starting time of the interval. Used for models x with piecewise-constant intensities fitted using the pci option to msm. The probabilities will be computed on the interval [t1, t1+t].

covariates

The covariate values at which to estimate the transition probabilities. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula, or a named list,

list (age = 60, sex = 1)

If some covariates are specified but not others, the missing ones default to zero.

For time-inhomogeneous models fitted using the pci option to msm, "covariates" here include only those specified using the covariates argument to msm, and exclude the artificial covariates representing the time period.

For time-inhomogeneous models fitted "by hand" by using a time-dependent covariate in the covariates argument to msm, the function pmatrix.piecewise.msm should be used to to calculate transition probabilities.

ci

If "normal", then calculate a confidence interval for the transition probabilities by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then calculating the resulting transition probability matrix for each replicate. See, e.g. Mandel (2013) for a discussion of this approach.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

If "none" (the default) then no confidence interval is calculated.

cl

Width of the symmetric confidence interval, relative to 1.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

qmatrix

A transition intensity matrix. Either this or a fitted model x must be supplied. No confidence intervals are available if qmatrix is supplied.

...

Optional arguments to be passed to MatrixExp to control the method of computing the matrix exponential.

Details

For a continuous-time homogeneous Markov process with transition intensity matrix QQ, the probability of occupying state ss at time u+tu + t conditionally on occupying state rr at time uu is given by the (r,s)(r,s) entry of the matrix P(t)=exp(tQ)P(t) = \exp(tQ), where exp()\exp() is the matrix exponential.

For non-homogeneous processes, where covariates and hence the transition intensity matrix QQ are piecewise-constant in time, the transition probability matrix is calculated as a product of matrices over a series of intervals, as explained in pmatrix.piecewise.msm.

The pmatrix.piecewise.msm function is only necessary for models fitted using a time-dependent covariate in the covariates argument to msm. For time-inhomogeneous models fitted using "pci", pmatrix.msm can be used, with arguments t and t1, to calculate transition probabilities over any time period.

Value

The matrix of estimated transition probabilities P(t)P(t) in the given time. Rows correspond to "from-state" and columns to "to-state".

Or if ci="normal" or ci="bootstrap", pmatrix.msm returns a list with components estimates and ci, where estimates is the matrix of estimated transition probabilities, and ci is a list of two matrices containing the upper and lower confidence limits.

Author(s)

C. H. Jackson [email protected].

References

Mandel, M. (2013). "Simulation based confidence intervals for functions with complicated derivatives." The American Statistician 67(2):76-81

See Also

qmatrix.msm, pmatrix.piecewise.msm, boot.msm


Transition probability matrix for processes with piecewise-constant intensities

Description

Extract the estimated transition probability matrix from a fitted non-time-homogeneous multi-state model for a given time interval. This is a generalisation of pmatrix.msm to models with time-dependent covariates. Note that pmatrix.msm is sufficient to calculate transition probabilities for time-inhomogeneous models fitted using the pci argument to msm.

Usage

pmatrix.piecewise.msm(
  x = NULL,
  t1,
  t2,
  times,
  covariates = NULL,
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL,
  qlist = NULL,
  ...
)

Arguments

x

A fitted multi-state model, as returned by msm. This should be a non-homogeneous model, whose transition intensity matrix depends on a time-dependent covariate.

t1

The start of the time interval to estimate the transition probabilities for.

t2

The end of the time interval to estimate the transition probabilities for.

times

Cut points at which the transition intensity matrix changes.

covariates

A list with number of components one greater than the length of times. Each component of the list is specified in the same way as the covariates argument to pmatrix.msm. The components correspond to the covariate values in the intervals

(t1, times[1]], (times[1], times[2]], ..., (times[length(times)], t2]

(assuming that all elements of times are in the interval (t1, t2)).

ci

If "normal", then calculate a confidence interval for the transition probabilities by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then calculating the resulting transition probability matrix for each replicate.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

If "none" (the default) then no confidence interval is calculated.

cl

Width of the symmetric confidence interval, relative to 1.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

qlist

A list of transition intensity matrices, of length one greater than the length of times. Either this or a fitted model x must be supplied. No confidence intervals are available if (just) qlist is supplied.

...

Optional arguments to be passed to MatrixExp to control the method of computing the matrix exponential.

Details

Suppose a multi-state model has been fitted, in which the transition intensity matrix Q(x(t))Q(x(t)) is modelled in terms of time-dependent covariates x(t)x(t). The transition probability matrix P(t1,tn)P(t_1, t_n) for the time interval (t1,(t_1,tn)t_n) cannot be calculated from the estimated intensity matrix as exp((tnt1)Q)\exp((t_n - t_1) Q), because QQ varies within the interval t1,tnt_1, t_n. However, if the covariates are piecewise-constant, or can be approximated as piecewise-constant, then we can calculate P(t1,tn)P(t_1, t_n) by multiplying together individual matrices P(ti,P(t_i,ti+1)=exp((ti+1ti)Q)t_{i+1}) = \exp((t_{i+1} - t_i) Q), calculated over intervals where Q is constant:

P(t1,tn)=P(t1,t2)P(t2,t3)P(tn1,P(t_1, t_n) = P(t_1, t_2) P(t_2, t_3)\ldots P(t_{n-1},

tn)t_n)

Value

The matrix of estimated transition probabilities P(t)P(t) for the time interval [t1, tn]. That is, the probabilities of occupying state ss at time tnt_n conditionally on occupying state rr at time t1t_1. Rows correspond to "from-state" and columns to "to-state".

Author(s)

C. H. Jackson [email protected]

See Also

pmatrix.msm

Examples

## Not run: 
## In a clinical study, suppose patients are given a placebo in the
## first 5 weeks, then they begin treatment 1 at 5 weeks, and
## a combination of treatments 1 and 2 from 10 weeks.
## Suppose a multi-state model x has been fitted for the patients'
## progress, with treat1 and treat2 as time dependent covariates.

## Cut points for when treatment covariate changes
times <- c(0, 5, 10)

## Indicators for which treatments are active in the four intervals
## defined by the three cut points
covariates <- list( list (treat1=0, treat2=0), list (treat1=0, treat2=0), list(treat1=1, treat2=0),
list(treat1=1, treat2=1) )

## Calculate transition probabilities from the start of the study to 15 weeks
pmatrix.piecewise.msm(x, 0, 15, times, covariates)

## End(Not run)

Probability of each state being next

Description

Compute a matrix of the probability of each state ss being the next state of the process after each state rr. Together with the mean sojourn times in each state (sojourn.msm), these fully define a continuous-time Markov model.

Usage

pnext.msm(
  x,
  covariates = "mean",
  ci = c("normal", "bootstrap", "delta", "none"),
  cl = 0.95,
  B = 1000,
  cores = NULL
)

Arguments

x

A fitted multi-state model, as returned by msm.

covariates

The covariate values at which to estimate the intensities. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula, or a named list,

list (age = 60, sex = 1)

ci

If "normal" (the default) then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then transforming.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

If "delta" then confidence intervals are calculated based on the delta method SEs of the log rates, but this is not recommended since it may not respect the constraint that probabilities are less than one.

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs.

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

Details

For a continuous-time Markov process in state rr, the probability that the next state is ss is qrs/qrr-q_{rs} / q_{rr}, where qrsq_{rs} is the transition intensity (qmatrix.msm).

A continuous-time Markov model is fully specified by these probabilities together with the mean sojourn times 1/qrr-1/q_{rr} in each state rr. This gives a more intuitively meaningful description of a model than the intensity matrix.

Remember that msm deals with continuous-time, not discrete-time models, so these are not the same as the probability of observing state ss at a fixed time in the future. Those probabilities are given by pmatrix.msm.

Value

The matrix of probabilities that the next move of a process in state rr (rows) is to state ss (columns).

Author(s)

C. H. Jackson [email protected]

See Also

qmatrix.msm,pmatrix.msm,qratio.msm


Passage probabilities

Description

Probabilities of having visited each state by a particular time in a continuous time Markov model.

Usage

ppass.msm(
  x = NULL,
  qmatrix = NULL,
  tot,
  start = "all",
  covariates = "mean",
  piecewise.times = NULL,
  piecewise.covariates = NULL,
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL,
  ...
)

Arguments

x

A fitted multi-state model, as returned by msm.

qmatrix

Instead of x, you can simply supply a transition intensity matrix in qmatrix.

tot

Finite time to forecast the passage probabilites for.

start

Starting state (integer). By default (start="all"), this will return a matrix one row for each starting state.

Alternatively, this can be used to obtain passage probabilities from a set of states, rather than single states. To achieve this, state is set to a vector of weights, with length equal to the number of states in the model. These weights should be proportional to the probability of starting in each of the states in the desired set, so that weights of zero are supplied for other states. The function will calculate the weighted average of the passage probabilities from each of the corresponding states.

covariates

Covariate values defining the intensity matrix for the fitted model x, as supplied to qmatrix.msm.

piecewise.times

For models with time-dependent covariates, this defines the cut points in time at which the transition intensity matrix changes. This is not required for models fitted with the pci option to msm, which are handled automatically.

piecewise.covariates

For models with time-dependent covariates, this is the list of covariates for each time period defined by piecewise.times, in the format documented for the covariates argument to pmatrix.piecewise.msm. This is not required for models fitted with the pci option to msm, which are handled automatically.

ci

If "normal", then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

If "none" (the default) then no confidence interval is calculated.

cl

Width of the symmetric confidence interval, relative to 1.

B

Number of bootstrap replicates.

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

...

Arguments to pass to MatrixExp.

Details

The passage probabilities to state ss are computed by setting the ssth row of the transition intensity matrix QQ to zero, giving an intensity matrix QQ^* for a simplified model structure where state ss is absorbing. The probabilities of passage are then equivalent to row ss of the transition probability matrix Exp(tQ)Exp(tQ^*) (pmatrix.msm) under this simplified model for t=t=tot.

For time-inhomogenous models, this process is generalised by calculating an intensity matrix for each time period, zeroing the appropriate row of each, and calculating and multiplying transition probability matrices as in pmatrix.piecewise.msm.

Note this is different from the probability of occupying each state at exactly time tt, given by pmatrix.msm. The passage probability allows for the possibility of having visited the state before tt, but then occupying a different state at tt.

The mean of the passage distribution is the expected first passage time, efpt.msm.

Value

A matrix whose r,sr, s entry is the probability of having visited state ss at least once before time tt, given the state at time 00 is rr. The diagonal entries should all be 1.

Author(s)

C. H. Jackson [email protected] with contributions from Jon Fintzi.

References

Norris, J. R. (1997) Markov Chains. Cambridge University Press.

See Also

efpt.msm, totlos.msm, boot.msm.

Examples

Q <- rbind(c(-0.5, 0.25, 0, 0.25), c(0.166, -0.498, 0.166, 0.166),
           c(0, 0.25, -0.5, 0.25), c(0, 0, 0, 0))

## ppass[1,2](t) converges to 0.5 with t, since given in state 1, the
## probability of going to the absorbing state 4 before visiting state
## 2 is 0.5, and the chance of still being in state 1 at t decreases.

ppass.msm(qmatrix=Q, tot=2)
ppass.msm(qmatrix=Q, tot=20)
ppass.msm(qmatrix=Q, tot=100)

Q <- Q[1:3,1:3]; diag(Q) <- 0; diag(Q) <- -rowSums(Q)

## Probability of about 1/2 of visiting state 3 by time 10.5, the
## median first passage time

ppass.msm(qmatrix=Q, tot=10.5)

## Mean first passage time from state 2 to state 3 is 10.02: similar
## to the median

efpt.msm(qmatrix=Q, tostate=3)

Tables of observed and expected prevalences

Description

This provides a rough indication of the goodness of fit of a multi-state model, by estimating the observed numbers of individuals occupying each state at a series of times, and comparing these with forecasts from the fitted model.

Usage

prevalence.msm(
  x,
  times = NULL,
  timezero = NULL,
  initstates = NULL,
  covariates = "population",
  misccovariates = "mean",
  piecewise.times = NULL,
  piecewise.covariates = NULL,
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL,
  interp = c("start", "midpoint"),
  censtime = Inf,
  subset = NULL,
  plot = FALSE,
  ...
)

Arguments

x

A fitted multi-state model produced by msm.

times

Series of times at which to compute the observed and expected prevalences of states.

timezero

Initial time of the Markov process. Expected values are forecasted from here. Defaults to the minimum of the observation times given in the data.

initstates

Optional vector of the same length as the number of states. Gives the numbers of individuals occupying each state at the initial time, to be used for forecasting expected prevalences. The default is those observed in the data. These should add up to the actual number of people in the study at the start.

covariates

Covariate values for which to forecast expected state occupancy. With the default covariates="population", expected prevalences are produced by summing model predictions over the covariates observed in the original data, for a fair comparison with the observed prevalences. This may be slow, particularly with continuous covariates.

Predictions for fixed covariates can be obtained by supplying covariate values in the standard way, as in qmatrix.msm. Therefore if covariates="population" is too slow, using the mean observed values through covariates="mean" may give a reasonable approximation.

This argument is ignored if piecewise.times is specified. If there are a mixture of time-constant and time-dependent covariates, then the values for all covariates should be supplied in piecewise.covariates.

misccovariates

(Misclassification models only) Values of covariates on the misclassification probability matrix for converting expected true to expected misclassified states. Ignored if covariates="population", otherwise defaults to the mean values of the covariates in the data set.

piecewise.times

Times at which piecewise-constant intensities change. See pmatrix.piecewise.msm for how to specify this. Ignored if covariates="population". This is only required for time-inhomogeneous models specified using explicit time-dependent covariates, and should not be used for models specified using "pci".

piecewise.covariates

Covariates on which the piecewise-constant intensities depend. See pmatrix.piecewise.msm for how to specify this. Ignored if covariates="population".

ci

If "normal", then calculate a confidence interval for the expected prevalences by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then calculating the expected prevalences for each replicate.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

If "none" (the default) then no confidence interval is calculated.

cl

Width of the symmetric confidence interval, relative to 1

B

Number of bootstrap replicates

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

interp

Suppose an individual was observed in states Sr1S_{r-1} and SrS_r at two consecutive times tr1t_{r-1} and trt_r, and we want to estimate 'observed' prevalences at a time tt between tr1t_{r-1} and trt_r.

If interp="start", then individuals are assumed to be in state Sr1S_{r-1} at time tt, the same state as they were at tr1t_{r-1}.

If interp="midpoint" then if t<=(tr1+tr)/2t <= (t_{r-1} + t_r) / 2, the midpoint of tr1t_{r-1} and trt_r, the state at tt is assumed to be Sr1S_{r-1}, otherwise SrS_{r}. This is generally more reasonable for "progressive" models.

censtime

Adjustment to the observed prevalences to account for limited follow-up in the data.

If the time is greater than censtime and the patient has reached an absorbing state, then that subject will be removed from the risk set. For example, if patients have died but would only have been observed up to this time, then this avoids overestimating the proportion of people who are dead at later times.

This can be supplied as a single value, or as a vector with one element per subject (after any subset has been taken), in the same order as the original data. This vector also only includes subjects with complete data, thus it excludes for example subjects with only one observation (thus no observed transitions), and subjects for whom every observation has missing values. (Note, to help construct this, the complete data used for the model fit can be accessed with model.frame(x), where x is the fitted model object)

This is ignored if it is less than the subject's maximum observation time.

subset

Subset of subjects to calculate observed prevalences for.

plot

Generate a plot of observed against expected prevalences. See plot.prevalence.msm

...

Further arguments to pass to plot.prevalence.msm.

Details

The fitted transition probability matrix is used to forecast expected prevalences from the state occupancy at the initial time. To produce the expected number in state jj at time tt after the start, the number of individuals under observation at time tt (including those who have died, but not those lost to follow-up) is multiplied by the product of the proportion of individuals in each state at the initial time and the transition probability matrix in the time interval tt. The proportion of individuals in each state at the "initial" time is estimated, if necessary, in the same way as the observed prevalences.

For misclassification models (fitted using an ematrix), this aims to assess the fit of the full model for the observed states. That is, the combined Markov progression model for the true states and the misclassification model. Thus, expected prevalences of true states are estimated from the assumed proportion occupying each state at the initial time using the fitted transition probabiliy matrix. The vector of expected prevalences of true states is then multiplied by the fitted misclassification probability matrix to obtain the expected prevalences of observed states.

For general hidden Markov models, the observed state is taken to be the predicted underlying state from the Viterbi algorithm (viterbi.msm). The goodness of fit of these states to the underlying Markov model is tested.

In any model, if there are censored states, then these are replaced by imputed values of highest probability from the Viterbi algorithm in order to calculate the observed state prevalences.

For an example of this approach, see Gentleman et al. (1994).

Value

A list of matrices, with components:

Observed

Table of observed numbers of individuals in each state at each time

Observed percentages

Corresponding percentage of the individuals at risk at each time.

Expected

Table of corresponding expected numbers.

Expected percentages

Corresponding percentage of the individuals at risk at each time.

Or if ci.boot = TRUE, the component Expected is a list with components estimates and ci.
estimates is a matrix of the expected prevalences, and ci is a list of two matrices, containing the confidence limits. The component Expected percentages has a similar format.

Author(s)

C. H. Jackson [email protected]

References

Gentleman, R.C., Lawless, J.F., Lindsey, J.C. and Yan, P. Multi-state Markov models for analysing incomplete disease history data with illustrations for HIV disease. Statistics in Medicine (1994) 13(3): 805–821.

Titman, A.C., Sharples, L. D. Model diagnostics for multi-state models. Statistical Methods in Medical Research (2010) 19(6):621-651.

See Also

msm, summary.msm


Print a fitted msm model object

Description

Print a fitted msm model object

Usage

## S3 method for class 'msm'
print(x, covariates = NULL, digits = 4, ...)

printnew.msm(x, covariates = NULL, digits = 4, ...)

Arguments

x

Output from msm, representing a fitted multi-state model object.

covariates

Covariates for which to print “baseline” transition intensities or misclassification probabilities. See qmatrix.msm for more details.

digits

Minimum number of significant digits, passed to format. Defaults to 4.

...

Other arguments to be passed to format.

Details

This is the new method of formatting msm objects for printing. The old method was based on printing lists of matrices. That produced a lot of wasted space for parameters which were zero, and it was difficult to match corresponding numbers between matrices. The new method presents all the transition intensities and covariate effects as a single compact table, and likewise for misclassification matrices.

Also in the old method, covariate effects were presented as log hazard ratios or log odds ratios. The log scale is more convenient mathematically, but unnatural to interpret. The new method presents hazard ratios for covariates on transition intensities and odds ratios for misclassification probabilities.

printnew.msm is an alias for print.msm.

Value

The object returned by print.msm is a numeric matrix with one column for each estimate or confidence limit for intensities and their covariates, in the same arrangement as printed, but with the underlying numbers in full precision. The results formatted for printing are stored in the "formatted" attribute of the object, as a character matrix. These can alternatively be produced by msm.form.qoutput, which has no printing side-effect. msm.form.eoutput produces the same arrangement for misclassification probabilities instead of intensities.

Author(s)

C. H. Jackson [email protected]

See Also

msm, printold.msm, msm.form.qoutput.


Print a fitted msm model object

Description

Print a fitted msm model object (in old format, from msm 1.3.1 and earlier)

Usage

printold.msm(x, ...)

Arguments

x

Output from msm, representing a fitted multi-state model object.

...

Other arguments to be passed to format.

Details

See print.msm for a better and cleaner output format, and an explanation of the change.

Author(s)

C. H. Jackson [email protected]

See Also

print.msm


Psoriatic arthritis data

Description

A series of observations of grades of psoriatic arthritis, as indicated by numbers of damaged joints.

Format

A data frame containing 806 observations, representing visits to a psoriatic arthritis (PsA) clinic from 305 patients. The rows are grouped by patient number and ordered by examination time. Each row represents an examination and contains additional covariates.

ptnum (numeric) Patient identification number
months (numeric) Examination time in months
state (numeric) Clinical state of PsA. Patients in states 1, 2, 3 and 4
have 0, 1 to 4, 5 to 9 and 10 or more damaged joints,
respectively.
hieffusn (numeric) Presence of five or more effusions
ollwsdrt (character) Erythrocyte sedimentation rate of less than 15 mm/h

References

Gladman, D. D. and Farewell, V.T. (1999) Progression in psoriatic arthritis: role of time-varying clinical indicators. J. Rheumatol. 26(11):2409-13

Examples

## Four-state progression-only model with high effusion and low
## sedimentation rate as covariates on the progression rates.  High
## effusion is assumed to have the same effect on the 1-2, 2-3, and 3-4
## progression rates, while low sedimentation rate has the same effect
## on the 1-2 and 2-3 intensities, but a different effect on the 3-4. 

data(psor)
psor.q <- rbind(c(0,0.1,0,0),c(0,0,0.1,0),c(0,0,0,0.1),c(0,0,0,0))
psor.msm <- msm(state ~ months, subject=ptnum, data=psor, 
                qmatrix = psor.q, covariates = ~ollwsdrt+hieffusn,
                constraint = list(hieffusn=c(1,1,1),ollwsdrt=c(1,1,2)),
                fixedpars=FALSE, control = list(REPORT=1,trace=2), method="BFGS")
qmatrix.msm(psor.msm)
sojourn.msm(psor.msm)
hazard.msm(psor.msm)

Developer documentation: model for covariates on transition intensities

Description

A list representing the model for covariates on transition intensities

Value

npars

Number of covariate effect parameters. This is defined as the number of covariates on intensities (with factors expanded as contrasts) multiplied by the number of allowed transitions in the model.

Note if msm was called with covariates set to a list of different covariates for different intensities, then this will include covariate effects that are implicitly defined as zero by this list. The information in paramdata objects can be used to identify wich ones are fixed at zero.

This also includes any timeperiod covariates in a time-inhomogeneous model defined by the pci option to msm.

ndpars

Number of distinct covariate effect parameters, as npars, but after any equality constraints have been applied.

ncovs

Number of covariates on intensities, with factors expanded as contrasts.

constr

List of equality constraints on these covariate effects, as supplied in the constraint argument to msm.

covlabels

Names / labels of these covariates in the model matrix (see model.matrix.msm).

inits

Initial values for these covariate effects, as a vector formed from the covinits list supplied to msm.

covmeans

Means of these covariates in the data (excluding data not required to fit the model, such as observations with missing data in other elements or subjects' last observations). This includes means of 0/1 factor contrasts as well as continuous covariates (for historic reasons, which may not be sensible).

See Also

msm.object.


Generic function to find quantiles of a distribution

Description

Generic function to find the quantiles of a distribution, given the equivalent probability distribution function.

Usage

qgeneric(pdist, p, special = NULL, ...)

Arguments

pdist

Probability distribution function, for example, pnorm for the normal distribution, which must be defined in the current workspace. This should accept and return vectorised parameters and values. It should also return the correct values for the entire real line, for example a positive distribution should have pdist(x)==0 for x<0x<0.

p

Vector of probabilities to find the quantiles for.

special

Vector of character strings naming arguments of the distribution function that should not be vectorised over. Used, for example, for the rate and t arguments in qpexp.

...

The remaining arguments define parameters of the distribution pdist. These MUST be named explicitly.

This may also contain the standard arguments log.p (logical; default FALSE, if TRUE, probabilities p are given as log(p)), and lower.tail (logical; if TRUE (default), probabilities are P[X <= x] otherwise, P[X > x].).

If the distribution is bounded above or below, then this should contain arguments lbound and ubound respectively, and these will be returned if p is 0 or 1 respectively. Defaults to -Inf and Inf respectively.

Details

This function is intended to enable users to define "q" functions for new distributions, in cases where the distribution function pdist is available analytically, but the quantile function is not.

It works by finding the root of the equation h(q)=pdist(q)p=0h(q) = pdist(q) - p = 0. Starting from the interval (1,1)(-1, 1), the interval width is expanded by 50% until h()h() is of opposite sign at either end. The root is then found using uniroot.

This assumes a suitably smooth, continuous distribution.

An identical function is provided in the flexsurv package.

Value

Vector of quantiles of the distribution at p.

Author(s)

Christopher Jackson <[email protected]>

Examples

qnorm(c(0.025, 0.975), 0, 1)
qgeneric(pnorm, c(0.025, 0.975), mean=0, sd=1) # must name the arguments

Transition intensity matrix

Description

Extract the estimated transition intensity matrix, and the corresponding standard errors, from a fitted multi-state model at a given set of covariate values.

Usage

qmatrix.msm(
  x,
  covariates = "mean",
  sojourn = FALSE,
  ci = c("delta", "normal", "bootstrap", "none"),
  cl = 0.95,
  B = 1000,
  cores = NULL
)

Arguments

x

A fitted multi-state model, as returned by msm.

covariates

The covariate values at which to estimate the intensity matrix. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula. Or more clearly, a named list,

list (age = 60, sex = 1)

If some covariates are specified but not others, the missing ones default to zero.

With covariates="mean", for factor / categorical variables, the mean of the 0/1 dummy variable for each factor level is used, representing an average over all values in the data, rather than a specific factor level.

sojourn

Set to TRUE if the estimated sojourn times and their standard errors should also be returned.

ci

If "delta" (the default) then confidence intervals are calculated by the delta method, or by simple transformation of the Hessian in the very simplest cases. Normality on the log scale is assumed.

If "normal", then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then transforming.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs.

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

Details

Transition intensities and covariate effects are estimated on the log scale by msm. A covariance matrix is estimated from the Hessian of the maximised log-likelihood.

A more practically meaningful parameterisation of a continuous-time Markov model with transition intensities qrsq_{rs} is in terms of the mean sojourn times 1/qrr-1 / q_{rr} in each state rr and the probabilities that the next move of the process when in state rr is to state ss, qrs/qrr-q_{rs} / q_{rr}.

Value

A list with components:

estimate

Estimated transition intensity matrix.

SE

Corresponding approximate standard errors.

L

Lower confidence limits

U

Upper confidence limits

Or if ci="none", then qmatrix.msm just returns the estimated transition intensity matrix.

If sojourn is TRUE, extra components called sojourn, sojournSE, sojournL and sojournU are included, containing the estimates, standard errors and confidence limits, respectively, of the mean sojourn times in each transient state.

The default print method for objects returned by qmatrix.msm presents estimates and confidence limits. To present estimates and standard errors, do something like

qmatrix.msm(x)[c("estimates","SE")]

Author(s)

C. H. Jackson [email protected]

See Also

pmatrix.msm, sojourn.msm, deltamethod, ematrix.msm


Developer documentation: transition model structure object

Description

A list giving information about the structure of states and allowed transitions in a multi-state model, and options for likelihood calculation. Used in internal computations, and returned in a fitted msm model object.

Value

nstates

Number of states

iso

Label for which basic structure the model is isomorphic to in the list of structures for which analytic formulae for the transition probabilities are implemented in the source file src/analyticp.c. This list is given by the internal object msm:::.msm.graphs which is defined and documented in the source file R/constants.R.

iso is 0 if the analytic P matrix is not implemented for this structure, or if analytic P matrix calculations are disabled using use.analyticp=FALSE in the call to msm.

perm

Permutation required to convert the base isomorphism into the structure of this model. A vector of integers whose rrth element is the state number in the base structure representing state rr in the current structure.

qperm

Inverse permutation: vector whose rrth element is the state number in the current structure representing the rrth state in the base structure.

npars

Number of allowed instantaneous transitions, equal to sum(imatrix).

imatrix

Indicator matrix for allowed instantaneous transitions. This has (r,s)(r,s) entry 1 if the transition from rr to ss is permitted in continuous time, and 0 otherwise. The diagonal entries are arbitrarily set to 0.

qmatrix

Matrix of initial values for the transition intensities, supplied as the qmatrix argument of msm.

inits

Vector of these initial values, reading across rows of qmatrix and excluding the diagonal and disallowed transitions.

constr

Indicators for equality constraints on baseline intensities, taken from the qconstraint argument to msm, and mapped if necessary to the set (1,2,3,...).

ndpars

Number of distinct allowed instantaneous transitions, after applying equality constraints.

expm

Use expm package to calculate matrix exponentials for likelihoods, as supplied to the use.expm argument of msm. TRUE or FALSE.

See Also

msm.object,emodel.object, hmodel.object.


Estimated ratio of transition intensities

Description

Compute the estimate and approximate standard error of the ratio of two estimated transition intensities from a fitted multi-state model at a given set of covariate values.

Usage

qratio.msm(
  x,
  ind1,
  ind2,
  covariates = "mean",
  ci = c("delta", "normal", "bootstrap", "none"),
  cl = 0.95,
  B = 1000,
  cores = NULL
)

Arguments

x

A fitted multi-state model, as returned by msm.

ind1

Pair of numbers giving the indices in the intensity matrix of the numerator of the ratio, for example, c(1,2).

ind2

Pair of numbers giving the indices in the intensity matrix of the denominator of the ratio, for example, c(2,1).

covariates

The covariate values at which to estimate the intensities. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula, or a named list,

list (age = 60, sex = 1)

ci

If "delta" (the default) then confidence intervals are calculated by the delta method.

If "normal", then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then transforming.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

Details

For example, we might want to compute the ratio of the progression rate and recovery rate for a fitted model disease.msm with a health state (state 1) and a disease state (state 2). In this case, the progression rate is the (1,2) entry of the intensity matrix, and the recovery rate is the (2,1) entry. Thus to compute this ratio with covariates set to their means, we call

qratio.msm(disease.msm, c(1,2), c(2,1)) .

Standard errors are estimated by the delta method. Confidence limits are estimated by assuming normality on the log scale.

Value

A named vector with elements estimate, se, L and U containing the estimate, standard error, lower and upper confidence limits, respectively, of the ratio of intensities.

Author(s)

C. H. Jackson [email protected]

See Also

qmatrix.msm


Convert data stored in msm object to old format

Description

Converts the data element of msm objects to the old format.

Usage

recreate.olddata(x)

Arguments

x

Object returned by the msm function, representing a fitted multi-state model.

Details

This is just provided for convenience and to illustrate the changes. It is not guaranteed to be complete, and is liable to be withdrawn. Users who were relying on the previous undocumented format are advised to upgrade their code to use the new format, which uses model frames and model design matrices in the standard format used in version 1.4, based on model.frame and model.matrix.

Value

A list of vectors and matrices in the undocumented ad-hoc format used for the data component of msm objects in msm versions 1.3.1 and earlier.


Score residuals

Description

Score residuals for detecting outlying subjects.

Usage

scoreresid.msm(x, plot = FALSE)

Arguments

x

A fitted multi-state model, as returned by msm.

plot

If TRUE, display a simple plot of the residuals in subject order, labelled by subject identifiers

Details

The score residual for a single subject is

U(θ)TI(θ)1U(θ)U(\theta)^T I(\theta)^{-1} U(\theta)

where U(θ)U(\theta) is the vector of first derivatives of the log-likelihood for that subject at maximum likelihood estimates θ\theta, and I(θ)I(\theta) is the observed Fisher information matrix, that is, the matrix of second derivatives of minus the log-likelihood for that subject at theta.

Subjects with a higher influence on the maximum likelihood estimates will have higher score residuals.

These are only available for models with analytic derivatives (which includes all non-hidden and most hidden Markov models).

Value

Vector of the residuals, named by subject identifiers.

Author(s)

Andrew Titman [email protected] (theory), Chris Jackson [email protected] (code)


Simulate one individual trajectory from a continuous-time Markov model

Description

Simulate one realisation from a continuous-time Markov process up to a given time.

Usage

sim.msm(
  qmatrix,
  maxtime,
  covs = NULL,
  beta = NULL,
  obstimes = 0,
  start = 1,
  mintime = 0
)

Arguments

qmatrix

The transition intensity matrix of the Markov process. The diagonal of qmatrix is ignored, and computed as appropriate so that the rows sum to zero. For example, a possible qmatrix for a three state illness-death model with recovery is:

rbind( c( 0, 0.1, 0.02 ), c( 0.1, 0, 0.01 ), c( 0, 0, 0 ) )

maxtime

Maximum time for the simulated process.

covs

Matrix of time-dependent covariates, with one row for each observation time and one column for each covariate.

beta

Matrix of linear covariate effects on log transition intensities. The rows correspond to different covariates, and the columns to the transition intensities. The intensities are ordered by reading across rows of the intensity matrix, starting with the first, counting the positive off-diagonal elements of the matrix.

obstimes

Vector of times at which the covariates are observed.

start

Starting state of the process. Defaults to 1.

mintime

Starting time of the process. Defaults to 0.

Details

The effect of time-dependent covariates on the transition intensity matrix for an individual is determined by assuming that the covariate is a step function which remains constant in between the individual's observation times.

Value

A list with components,

states

Simulated states through which the process moves. This ends with either an absorption before obstime, or a transient state at obstime.

times

Exact times at which the process changes to the corresponding states

qmatrix

The given transition intensity matrix

Author(s)

C. H. Jackson [email protected]

See Also

simmulti.msm

Examples

qmatrix <- rbind(
                 c(-0.2,   0.1,  0.1 ),
                 c(0.5,   -0.6,  0.1 ),
                 c(0,  0,  0)
                 )
sim.msm(qmatrix, 30)

Simulate from a Markov model fitted using msm

Description

Simulate a dataset from a Markov model fitted using msm, using the maximum likelihood estimates as parameters, and the same observation times as in the original data.

Usage

simfitted.msm(x, drop.absorb = TRUE, drop.pci.imp = TRUE)

Arguments

x

A fitted multi-state model object as returned by msm.

drop.absorb

Should repeated observations in an absorbing state be omitted. Use the default of TRUE to avoid warnings when using the simulated dataset for further msm fits. Or set to FALSE if exactly the same number of observations as the original data are needed.

drop.pci.imp

In time-inhomogeneous models fitted using the pci option to msm, censored observations are inserted into the data by msm at the times where the intensity changes, but dropped by default when simulating from the fitted model using this function. Set this argument to FALSE to keep these observations and the corresponding indicator variable.

Details

This function is a wrapper around simmulti.msm, and only simulates panel-observed data. To generate datasets with the exact times of transition, use the lower-level sim.msm.

Markov models with misclassified states fitted through the ematrix option to msm are supported, but not general hidden Markov models with hmodel. For misclassification models, this function includes misclassification in the simulated states.

This function is used for parametric bootstrapping to estimate the null distribution of the test statistic in pearson.msm.

Value

A dataset with variables as described in simmulti.msm.

Author(s)

C. H. Jackson [email protected]

See Also

simmulti.msm, sim.msm, pearson.msm, msm.


Simulate multiple trajectories from a multi-state Markov model with arbitrary observation times

Description

Simulate a number of individual realisations from a continuous-time Markov process. Observations of the process are made at specified arbitrary times for each individual, giving panel-observed data.

Usage

simmulti.msm(
  data,
  qmatrix,
  covariates = NULL,
  death = FALSE,
  start,
  ematrix = NULL,
  misccovariates = NULL,
  hmodel = NULL,
  hcovariates = NULL,
  censor.states = NULL,
  drop.absorb = TRUE
)

Arguments

data

A data frame with a mandatory column named time, representing observation times. The optional column named subject, corresponds to subject identification numbers. If not given, all observations are assumed to be on the same individual. Observation times should be sorted within individuals. The optional column named cens indicates the times at which simulated states should be censored. If cens==0 then the state is not censored, and if cens==k, say, then all simulated states at that time which are in the set censor.states are replaced by k. Other named columns of the data frame represent any covariates, which may be time-constant or time-dependent. Time-dependent covariates are assumed to be constant between the observation times.

qmatrix

The transition intensity matrix of the Markov process, with any covariates set to zero. The diagonal of qmatrix is ignored, and computed as appropriate so that the rows sum to zero. For example, a possible qmatrix for a three state illness-death model with recovery is:

rbind( c( 0, 0.1, 0.02 ), c( 0.1, 0, 0.01 ), c( 0, 0, 0 ) )

covariates

List of linear covariate effects on log transition intensities. Each element is a vector of the effects of one covariate on all the transition intensities. The intensities are ordered by reading across rows of the intensity matrix, starting with the first, counting the positive off-diagonal elements of the matrix.

For example, for a multi-state model with three transition intensities, and two covariates x and y on each intensity,

covariates=list(x = c(-0.3,-0.3,-0.3), y=c(0.1, 0.1, 0.1))

death

Vector of indices of the death states. A death state is an absorbing state whose time of entry is known exactly, but the individual is assumed to be in an unknown transient state ("alive") at the previous instant. This is the usual situation for times of death in chronic disease monitoring data. For example, if you specify death = c(4, 5) then states 4 and 5 are assumed to be death states.

death = TRUE indicates that the final state is a death state, and death = FALSE (the default) indicates that there is no death state.

start

A vector with the same number of elements as there are distinct subjects in the data, giving the states in which each corresponding individual begins. Or a single number, if all of these are the same. Defaults to state 1 for each subject.

ematrix

An optional misclassification matrix for generating observed states conditionally on the simulated true states. As defined in msm.

misccovariates

Covariate effects on misclassification probabilities via multinomial logistic regression. Linear effects operate on the log of each probability relative to the probability of classification in the correct state. In same format as covariates.

hmodel

An optional hidden Markov model for generating observed outcomes conditionally on the simulated true states. As defined in msm. Multivariate outcomes (hmmMV) are not supported.

hcovariates

List of the same length as hmodel, defining any covariates governing the hidden Markov outcome models. Unlike in the msm function, this should also define the values of the covariate effects. Each element of the list is a named vector of the initial values for each set of covariates for that state. For example, for a three-state hidden Markov model with two, one and no covariates on the state 1, 2 and 3 outcome models respectively,

hcovariates = list (c(acute=-8, age=0), c(acute=-8), NULL)

censor.states

Set of simulated states which should be replaced by a censoring indicator at censoring times. By default this is all transient states (representing alive, with unknown state).

drop.absorb

Drop repeated observations in the absorbing state, retaining only one.

Details

sim.msm is called repeatedly to produce a simulated trajectory for each individual. The state at each specified observation time is then taken to produce a new column state. The effect of time-dependent covariates on the transition intensity matrix for an individual is determined by assuming that the covariate is a step function which remains constant in between the individual's observation times. If the subject enters an absorbing state, then only the first observation in that state is kept in the data frame. Rows corresponding to future observations are deleted. The entry times into states given in death are assumed to be known exactly.

Value

A data frame with columns,

subject

Subject identification indicators

time

Observation times

state

Simulated (true) state at the corresponding time

obs

Observed outcome at the corresponding time, if ematrix or hmodel was supplied

keep

Row numbers of the original data. Useful when drop.absorb=TRUE, to show which rows were not dropped

plus any supplied covariates.

Author(s)

C. H. Jackson [email protected]

See Also

sim.msm

Examples

### Simulate 100 individuals with common observation times
sim.df <- data.frame(subject = rep(1:100, rep(13,100)), time = rep(seq(0, 24, 2), 100))
qmatrix <- rbind(c(-0.11,   0.1,  0.01 ),
                 c(0.05,   -0.15,  0.1 ),
                 c(0.02,   0.07, -0.09))
simmulti.msm(sim.df, qmatrix)

Mean sojourn times from a multi-state model

Description

Estimate the mean sojourn times in the transient states of a multi-state model and their confidence limits.

Usage

sojourn.msm(
  x,
  covariates = "mean",
  ci = c("delta", "normal", "bootstrap", "none"),
  cl = 0.95,
  B = 1000
)

Arguments

x

A fitted multi-state model, as returned by msm.

covariates

The covariate values at which to estimate the mean sojourn times. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

a list of values, with optional names. For example,

list(60, 1), where the order of the list follows the order of the covariates originally given in the model formula, or a named list, e.g.

list (age = 60, sex = 1)

ci

If "delta" (the default) then confidence intervals are calculated by the delta method, or by simple transformation of the Hessian in the very simplest cases.

If "normal", then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then transforming.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

cl

Width of the symmetric confidence interval to present. Defaults to 0.95.

B

Number of bootstrap replicates, or number of normal simulations from the distribution of the MLEs

Details

The mean sojourn time in a transient state rr is estimated by 1/qrr- 1 / q_{rr}, where qrrq_{rr} is the rrth entry on the diagonal of the estimated transition intensity matrix.

A continuous-time Markov model is fully specified by the mean sojourn times and the probability that each state is next (pnext.msm). This is a more intuitively meaningful description of a model than the transition intensity matrix (qmatrix.msm).

Time dependent covariates, or time-inhomogeneous models, are not supported. This would require the mean of a piecewise exponential distribution, and the package author is not aware of any general analytic form for that.

Value

A data frame with components:

estimates

Estimated mean sojourn times in the transient states.

SE

Corresponding standard errors.

L

Lower confidence limits.

U

Upper confidence limits.

Author(s)

C. H. Jackson [email protected]

See Also

msm, qmatrix.msm, deltamethod


Table of transitions

Description

Calculates a frequency table counting the number of times each pair of states were observed in successive observation times. This can be a useful way of summarising multi-state data.

Usage

statetable.msm(state, subject, data = NULL)

Arguments

state

Observed states, assumed to be ordered by time within each subject.

subject

Subject identification numbers corresponding to state. If not given, all observations are assumed to be on the same subject.

data

An optional data frame in which the variables represented by subject and state can be found.

Details

If the data are intermittently observed (panel data) this table should not be used to decide what transitions should be allowed in the QQ matrix, which works in continuous time. This function counts the transitions between states over a time interval, not in real time. There can be observed transitions between state rr and ss over an interval even if qrs=0q_{rs}=0, because the process may have passed through one or more intermediate states in the middle of the interval.

Value

A frequency table with starting states as rows and finishing states as columns.

Author(s)

C. H. Jackson [email protected]

See Also

crudeinits.msm

Examples

## Heart transplant data
data(cav)

## 148 deaths from state 1, 48 from state 2 and 55 from state 3.
statetable.msm(state, PTNUM, data=cav)

Summarise a fitted multi-state model

Description

Summary method for fitted msm models. This is simply a wrapper around prevalence.msm which produces a table of observed and expected state prevalences for each time, and for models with covariates, hazard.msm to print hazard ratios with 95% confidence intervals for covariate effects.

Usage

## S3 method for class 'msm'
summary(object, hazard.scale = 1, ...)

Arguments

object

A fitted multi-state model object, as returned by msm.

hazard.scale

Vector with same elements as number of covariates on transition rates. Corresponds to the increase in each covariate used to calculate its hazard ratio. Defaults to all 1.

...

Further arguments passed to prevalence.msm.

Value

A list of class summary.msm, with components:

prevalences

Output from prevalence.msm.

hazard

Output from hazard.msm.

hazard.scale

Value of the hazard.scale argument.

Author(s)

C. H. Jackson [email protected]

See Also

msm,prevalence.msm, hazard.msm


Explore the likelihood surface

Description

Plot the log-likelihood surface with respect to two parameters.

Usage

surface.msm(
  x,
  params = c(1, 2),
  np = 10,
  type = c("contour", "filled.contour", "persp", "image"),
  point = NULL,
  xrange = NULL,
  yrange = NULL,
  ...
)

## S3 method for class 'msm'
contour(x, ...)

## S3 method for class 'msm'
persp(x, ...)

## S3 method for class 'msm'
image(x, ...)

Arguments

x

Output from msm, representing a fitted msm model.

params

Integer vector with two elements, giving the indices of the parameters to vary. All other parameters will be fixed. Defaults to c(1,2), representing the first two log transition intensities. See the fixedpars argument to msm for a definition of these indices.

np

Number of grid points to use in each direction, by default 10. An np x np grid will be used to evaluate the likelihood surface. If 100 likelihood function evaluations is slow, then reduce this.

type

Character string specifying the type of plot to produce.

"contour" Contour plot, using the R function contour.
"filled.contour" Solid-color contour plot, using the R function filled.contour.
"persp" Perspective plot, using the R function persp.
"image" Grid color plot, using the R function image.
point

Vector of length n, where n is the number of parameters in the model, including the parameters that will be varied here. This specifies the point at which to fix the likelihood. By default, this is the maximum likelihood estimates stored in the fitted model x, x$estimates.

xrange

Range to plot for the first varied parameter. Defaults to plus and minus two standard errors, obtained from the Hessian at the maximum likelihood estimate.

yrange

Range to plot for the second varied parameter. Defaults to plus and minus two standard errors, obtained from the Hessian at the maximum likelihood estimate.

...

Further arguments to be passed to the plotting function.

Details

Draws a contour or perspective plot. Useful for diagnosing irregularities in the likelihood surface. If you want to use these plots before running the maximum likelihood estimation, then just run msm with all estimates fixed at their initial values.

contour.msm just calls surface.msm with type = "contour".

persp.msm just calls surface.msm with type = "persp".

image.msm just calls surface.msm with type = "image".

As these three functions are methods of the generic functions contour, persp and image, they can be invoked as contour(x), persp(x) or image(x), where x is a fitted msm object.

Author(s)

C. H. Jackson [email protected]

See Also

msm, contour, filled.contour, persp, image.


Tidy the parameter estimates from an msm model

Description

Tidy the parameter estimates from an msm model

Usage

## S3 method for class 'msm'
tidy(x, ...)

Arguments

x

Object returned by msm, representing a fitted multi-state model.

...

Other arguments (currently unused).

Value

A "tibble", with one row for each parameter and the following columns describing the parameter.

  • parclass: Class of parameters: intens (transition intensities), hr (hazard ratios representing effects of covariates on intensities), and their transformed versions logintens (log intensities) and loghr (log hazard ratios).

    For "misclassification" models fitted with the ematrix argument to msm, other classes of parameters include misc (misclassification probabilities), logitmisc (misclassification log odds), or_misc and logor_misc (effects of covariates on misclassification probabilities, as odds ratios or log odds ratios, with the first state as the reference category).

    For hidden Markov models fitted with the hmodel argument to msm, the parameter class called hmm comprises the parameters of the distributions of the outcome conditionally on the hidden state. Covariates on the location parameter of these distributions are included in class hmmcov. If initial state occupancy probabilities are estimated, these are included in class initp (or initlogodds for the log odds transforms of these), and any covariates on these probabilities are included in class initpcov.

  • state: Starting state of the transition for transition intensities, and true state for misclassification probabilities or hidden Markov model parameters.

  • tostate: Ending state of the transition for transition intensities, and observed state for misclassification probabilities

  • term: Name of the covariate for covariate effects, or "baseline" for the baseline intensity or analogous parameter value. Note that the "baseline" parameters are the parameters with covariates set to their mean values in the data (stored in e.g. x$qcmodel$covmeans), unless msm was called with center=FALSE.

  • estimate, std.error, conf.low, conf.high: Parameter estimate, standard error, and lower and upper confidence limits.

  • statistic, p.value: For covariate effects, the Z-test statistic and p-value for a test of the null hypothesis that the covariate effect is zero, based on the estimate and standard error.


Tidy the output of pmatrix.msm and similar functions

Description

This is the method for the generic 'tidy' function that is used for tidying the output of qmatrix.msm, pmatrix.msm, ematrix.msm, pnext.msm or ppass.msm. This should be called as tidy(), not tidy.msm.est() or tidy.qmatrix() or anything else.

Usage

## S3 method for class 'msm.est'
tidy(x, ...)

Arguments

x

Output of qmatrix.msm, pmatrix.msm, ematrix.msm, pnext.msm or ppass.msm, which all return objects of class "msm.est".

...

Further arguments (unused).


Tidy the output of totlos.msm and similar functions

Description

Note this should be called as tidy() not tidy.msm.totlos() or anything else, as this is a method for the generic tidy() function.

Usage

## S3 method for class 'msm.estbystate'
tidy(x, ...)

Arguments

x

Output of totlos.msm, envisits.msm or efpt.msm, which return objects of class "msm.estbystate".

...

Further arguments (unused).

Value

A tibble with one row per state, and columns for the estimate, and confidence intervals if available.


Tidy the output of prevalence.msm

Description

Note this should be called as tidy() not tidy.msm.prevalence() or anything else, as this is a method for the generic tidy() function.

Usage

## S3 method for class 'msm.prevalence'
tidy(x, ...)

Arguments

x

Output of prevalence.msm.

...

Further arguments (unused).

Value

A tibble with one row per combination of output type (count or percentage) and state, and columns for observed value, expected value and confidence limits for the expected value (if available).


Truncated Normal distribution

Description

Density, distribution function, quantile function and random generation for the truncated Normal distribution with mean equal to mean and standard deviation equal to sd before truncation, and truncated on the interval [lower, upper].

Usage

dtnorm(x, mean = 0, sd = 1, lower = -Inf, upper = Inf, log = FALSE)

ptnorm(
  q,
  mean = 0,
  sd = 1,
  lower = -Inf,
  upper = Inf,
  lower.tail = TRUE,
  log.p = FALSE
)

qtnorm(
  p,
  mean = 0,
  sd = 1,
  lower = -Inf,
  upper = Inf,
  lower.tail = TRUE,
  log.p = FALSE
)

rtnorm(n, mean = 0, sd = 1, lower = -Inf, upper = Inf)

Arguments

x, q

vector of quantiles.

mean

vector of means.

sd

vector of standard deviations.

lower

lower truncation point.

upper

upper truncation point.

log

logical; if TRUE, return log density or log hazard.

lower.tail

logical; if TRUE (default), probabilities are P[X <= x], otherwise, P[X > x].

log.p

logical; if TRUE, probabilities p are given as log(p).

p

vector of probabilities.

n

number of observations. If length(n) > 1, the length is taken to be the number required.

Details

The truncated normal distribution has density

f(x,μ,σ)=ϕ(x,μ,σ)/(Φ(u,μ,σ)Φ(l,μ,σ))f(x, \mu, \sigma) = \phi(x, \mu, \sigma) / (\Phi(u, \mu, \sigma) - \Phi(l, \mu, \sigma))

for l<=x<=ul <= x <= u, and 0 otherwise.

μ\mu is the mean of the original Normal distribution before truncation,
σ\sigma is the corresponding standard deviation,
uu is the upper truncation point,
ll is the lower truncation point,
ϕ(x)\phi(x) is the density of the corresponding normal distribution, and
Φ(x)\Phi(x) is the distribution function of the corresponding normal distribution.

If mean or sd are not specified they assume the default values of 0 and 1, respectively.

If lower or upper are not specified they assume the default values of -Inf and Inf, respectively, corresponding to no lower or no upper truncation.

Therefore, for example, dtnorm(x), with no other arguments, is simply equivalent to dnorm(x).

Only rtnorm is used in the msm package, to simulate from hidden Markov models with truncated normal distributions. This uses the rejection sampling algorithms described by Robert (1995).

These functions are merely provided for completion, and are not optimized for numerical stability or speed. To fit a hidden Markov model with a truncated Normal response distribution, use a hmmTNorm constructor. See the hmm-dists help page for further details.

Value

dtnorm gives the density, ptnorm gives the distribution function, qtnorm gives the quantile function, and rtnorm generates random deviates.

Author(s)

C. H. Jackson [email protected]

References

Robert, C. P. Simulation of truncated normal variables. Statistics and Computing (1995) 5, 121–125

See Also

dnorm

Examples

x <- seq(50, 90, by=1)
plot(x, dnorm(x, 70, 10), type="l", ylim=c(0,0.06)) ## standard Normal distribution
lines(x, dtnorm(x, 70, 10, 60, 80), type="l")       ## truncated Normal distribution

Total length of stay, or expected number of visits

Description

Estimate the expected total length of stay, or the expected number of visits, in each state, for an individual in a given period of evolution of a multi-state model.

Usage

totlos.msm(
  x,
  start = 1,
  end = NULL,
  fromt = 0,
  tot = Inf,
  covariates = "mean",
  piecewise.times = NULL,
  piecewise.covariates = NULL,
  num.integ = FALSE,
  discount = 0,
  env = FALSE,
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL,
  ...
)

envisits.msm(
  x = NULL,
  start = 1,
  end = NULL,
  fromt = 0,
  tot = Inf,
  covariates = "mean",
  piecewise.times = NULL,
  piecewise.covariates = NULL,
  num.integ = FALSE,
  discount = 0,
  ci = c("none", "normal", "bootstrap"),
  cl = 0.95,
  B = 1000,
  cores = NULL,
  ...
)

Arguments

x

A fitted multi-state model, as returned by msm.

start

Either a single number giving the state at the beginning of the period, or a vector of probabilities of being in each state at this time.

end

States to estimate the total length of stay (or number of visits) in. Defaults to all states. This is deprecated, since with the analytic solution (see "Details") it doesn't save any computation to only estimate for a subset of states.

fromt

Time from which to estimate. Defaults to 0, the beginning of the process.

tot

Time up to which the estimate is made. Defaults to infinity, giving the expected time spent in or number of visits to the state until absorption. However, the calculation will be much more efficient if a finite (potentially large) time is specified: see the "Details" section. For models without an absorbing state, t must be specified.

covariates

The covariate values to estimate for. This can either be:

the string "mean", denoting the means of the covariates in the data (this is the default),

the number 0, indicating that all the covariates should be set to zero,

or a list of values, with optional names. For example

list (60, 1)

where the order of the list follows the order of the covariates originally given in the model formula, or a named list,

list (age = 60, sex = 1)

piecewise.times

Times at which piecewise-constant intensities change. See pmatrix.piecewise.msm for how to specify this. This is only required for time-inhomogeneous models specified using explicit time-dependent covariates, and should not be used for models specified using "pci".

piecewise.covariates

Covariates on which the piecewise-constant intensities depend. See pmatrix.piecewise.msm for how to specify this.

num.integ

Use numerical integration instead of analytic solution (see below).

discount

Discount rate in continuous time.

env

Supplied to totlos.msm. If TRUE, return the expected number of visits to each state. If FALSE, return the total length of stay in each state. envisits.msm simply calls totlos.msm with env=TRUE.

ci

If "normal", then calculate a confidence interval by simulating B random vectors from the asymptotic multivariate normal distribution implied by the maximum likelihood estimates (and covariance matrix) of the log transition intensities and covariate effects, then calculating the total length of stay for each replicate.

If "bootstrap" then calculate a confidence interval by non-parametric bootstrap refitting. This is 1-2 orders of magnitude slower than the "normal" method, but is expected to be more accurate. See boot.msm for more details of bootstrapping in msm.

If "none" (the default) then no confidence interval is calculated.

cl

Width of the symmetric confidence interval, relative to 1

B

Number of bootstrap replicates

cores

Number of cores to use for bootstrapping using parallel processing. See boot.msm for more details.

...

Further arguments to be passed to the integrate function to control the numerical integration.

Details

The expected total length of stay in state jj between times t1t_1 and t2t_2, from the point of view of an individual in state ii at time 0, is defined by the integral from t1t_1 to t2t_2 of the i,ji,j entry of the transition probability matrix P(t)=Exp(tQ)P(t) = Exp(tQ), where QQ is the transition intensity matrix.

The corresponding expected number of visits to state jj (excluding the stay in the current state at time 0) is i!=jTiQi,j\sum_{i!=j} T_i Q_{i,j}, where TiT_i is the expected amount of time spent in state ii.

More generally, suppose that π0\pi_0 is the vector of probabilities of being in each state at time 0, supplied in start, and we want the vector x\mathbf{x} giving the expected lengths of stay in each state. The corresponding integral has the following solution (van Loan 1978; van Rosmalen et al. 2013)

x=[10K]Exp(tQ)[0KIK]\mathbf{x} = \left[ \begin{array}{ll} 1 & \mathbf{0}_K \end{array} \right] Exp(t Q') \left[ \begin{array}{l} \mathbf{0}_K\\I_K \end{array} \right]

where

Q=[0π00KQrIK]Q' = \left[ \begin{array}{ll} 0 & \mathbf{\pi}_0\\ \mathbf{0}_K & Q - rI_K \end{array} \right]

π0\pi_0 is the row vector of initial state probabilities supplied in start, 0K\mathbf{0}_K is the row vector of K zeros, rr is the discount rate, IKI_K is the K x K identity matrix, and ExpExp is the matrix exponential.

Alternatively, the integrals can be calculated numerically, using the integrate function. This may take a long time for models with many states where P(t)P(t) is expensive to calculate. This is required where tot = Inf, since the package author is not aware of any analytic expression for the limit of the above formula as tt goes to infinity.

With the argument num.integ=TRUE, numerical integration is used even where the analytic solution is available. This facility is just provided for checking results against versions 1.2.4 and earlier, and will be removed eventually. Please let the package maintainer know if any results are different.

For a model where the individual has only one place to go from each state, and each state is visited only once, for example a progressive disease model with no recovery or death, these are equal to the mean sojourn time in each state. However, consider a three-state health-disease-death model with transitions from health to disease, health to death, and disease to death, where everybody starts healthy. In this case the mean sojourn time in the disease state will be greater than the expected length of stay in the disease state. This is because the mean sojourn time in a state is conditional on entering the state, whereas the expected total time diseased is a forecast for a healthy individual, who may die before getting the disease.

In the above formulae, QQ is assumed to be constant over time, but the results generalise easily to piecewise-constant intensities. This function automatically handles models fitted using the pci option to msm. For any other inhomogeneous models, the user must specify piecewise.times and piecewise.covariates arguments to totlos.msm.

Value

A vector of expected total lengths of stay (totlos.msm), or expected number of visits (envisits.msm), for each transient state.

Author(s)

C. H. Jackson [email protected]

References

C. van Loan (1978). Computing integrals involving the matrix exponential. IEEE Transactions on Automatic Control 23(3)395-404.

J. van Rosmalen, M. Toy and J.F. O'Mahony (2013). A mathematical approach for evaluating Markov models in continuous time without discrete-event simulation. Medical Decision Making 33:767-779.

See Also

sojourn.msm, pmatrix.msm, integrate, boot.msm.


Transient and absorbing states

Description

Returns the transient and absorbing states of either a fitted model or a transition intensity matrix.

Usage

transient.msm(x = NULL, qmatrix = NULL)

absorbing.msm(x = NULL, qmatrix = NULL)

Arguments

x

A fitted multi-state model as returned by msm.

qmatrix

A transition intensity matrix. The diagonal is ignored and taken to be minus the sum of the rest of the row.

Value

A vector of the ordinal indices of the transient or absorbing states.

Author(s)

C. H. Jackson [email protected]


Coxian phase-type distribution with two phases

Description

Density, distribution, quantile functions and other utilities for the Coxian phase-type distribution with two phases.

Usage

d2phase(x, l1, mu1, mu2, log = FALSE)

p2phase(q, l1, mu1, mu2, lower.tail = TRUE, log.p = FALSE)

q2phase(p, l1, mu1, mu2, lower.tail = TRUE, log.p = FALSE)

r2phase(n, l1, mu1, mu2)

h2phase(x, l1, mu1, mu2, log = FALSE)

Arguments

x, q

vector of quantiles.

l1

Intensity for transition between phase 1 and phase 2.

mu1

Intensity for transition from phase 1 to exit.

mu2

Intensity for transition from phase 2 to exit.

log

logical; if TRUE, return log density or log hazard.

lower.tail

logical; if TRUE (default), probabilities are P[X <= x], otherwise, P[X > x].

log.p

logical; if TRUE, probabilities p are given as log(p).

p

vector of probabilities.

n

number of observations. If length(n) > 1, the length is taken to be the number required.

Details

This is the distribution of the time to reach state 3 in a continuous-time Markov model with three states and transitions permitted from state 1 to state 2 (with intensity λ1\lambda_1) state 1 to state 3 (intensity μ1\mu_1) and state 2 to state 3 (intensity μ2\mu_2). States 1 and 2 are the two "phases" and state 3 is the "exit" state.

The density is

f(tλ1,μ1)=e(λ1+μ1)t(μ1+(λ1+μ1)λ1t)f(t | \lambda_1, \mu_1) = e^{-(\lambda_1+\mu_1)t}(\mu_1 + (\lambda_1+\mu_1)\lambda_1 t)

if λ1+μ1=μ2\lambda_1 + \mu_1 = \mu_2, and

f(tλ1,μ1,μ2)=(λ1+μ1)e(λ1+μ1)t(μ2μ1)+μ2λ1eμ2tλ1+μ1μ2f(t | \lambda_1, \mu_1, \mu_2) = \frac{(\lambda_1+\mu_1)e^{-(\lambda_1+\mu_1)t}(\mu_2-\mu_1) + \mu_2\lambda_1e^{-\mu_2t}}{\lambda_1+\mu_1-\mu_2}

otherwise. The distribution function is

F(tλ1,μ1)=1e(λ1+μ1)t(1+λ1t)F(t | \lambda_1, \mu_1) = 1 - e^{-(\lambda_1+\mu_1) t} (1 + \lambda_1 t)

if λ1+μ1=μ2\lambda_1 + \mu_1 = \mu_2, and

F(tλ1,μ1,μ2)=1e(λ1+μ1)t(μ2μ1)+λ1eμ2tλ1+μ1μ2F(t | \lambda_1, \mu_1, \mu_2) = 1 - \frac{e^{-(\lambda_1 + \mu_1)t} (\mu_2 - \mu_1) + \lambda_1 e^{-\mu_2 t}}{ \lambda_1 + \mu_1 - \mu_2}

otherwise. Quantiles are calculated by numerically inverting the distribution function.

The mean is (1+λ1/μ2)/(λ1+μ1)(1 + \lambda_1/\mu_2) / (\lambda_1 + \mu_1).

The variance is (2+2λ1(λ1+μ1+μ2)/μ22(1+λ1/μ2)2)/(λ1+μ1)2(2 + 2\lambda_1(\lambda_1+\mu_1+ \mu_2)/\mu_2^2 - (1 + \lambda_1/\mu_2)^2)/(\lambda_1+\mu_1)^2.

If μ1=μ2\mu_1=\mu_2 it reduces to an exponential distribution with rate μ1\mu_1, and the parameter λ1\lambda_1 is redundant. Or also if λ1=0\lambda_1=0.

The hazard at x=0x=0 is μ1\mu_1, and smoothly increasing if μ1<μ2\mu_1<\mu_2. If λ1+μ1μ2\lambda_1 + \mu_1 \geq \mu_2 it increases to an asymptote of μ2\mu_2, and if λ1+μ1μ2\lambda_1 + \mu_1 \leq \mu_2 it increases to an asymptote of λ1+μ1\lambda_1 + \mu_1. The hazard is decreasing if μ1>μ2\mu_1>\mu_2, to an asymptote of μ2\mu_2.

Value

d2phase gives the density, p2phase gives the distribution function, q2phase gives the quantile function, r2phase generates random deviates, and h2phase gives the hazard.

Alternative parameterisation

An individual following this distribution can be seen as coming from a mixture of two populations:

1) "short stayers" whose mean sojourn time is M1=M_1 =1/(λ1+μ1)1/(\lambda_1+\mu_1) and sojourn distribution is exponential with rate λ1+μ1\lambda_1 + \mu_1.

2) "long stayers" whose mean sojourn time M2=M_2 =1/(λ1+μ1)+1/μ21/(\lambda_1+\mu_1) + 1/\mu_2 and sojourn distribution is the sum of two exponentials with rate λ1+\lambda_1 +μ1\mu_1 and μ2\mu_2 respectively. The individual is a "long stayer" with probability p=λ1/(λ1+μ1)p=\lambda_1/(\lambda_1 + \mu_1).

Thus a two-phase distribution can be more intuitively parameterised by the short and long stay means M1<M2M_1 < M_2 and the long stay probability pp. Given these parameters, the transition intensities are λ1=p/M1\lambda_1=p/M_1, μ1=(1p)/M1\mu_1=(1-p)/M_1, and μ2=1/(M2M1)\mu_2=1/(M_2-M_1). This can be useful for choosing intuitively reasonable initial values for procedures to fit these models to data.

The hazard is increasing at least if M2<2M1M_2 < 2M_1, and also only if (M22M1)/(M2M1)<p(M_2 - 2M_1)/(M_2 - M_1) < p.

For increasing hazards with λ1+μ1μ2\lambda_1 + \mu_1 \leq \mu_2, the maximum hazard ratio between any time tt and time 0 is 1/(1p)1/(1-p).

For increasing hazards with λ1+μ1μ2\lambda_1 + \mu_1 \geq \mu_2, the maximum hazard ratio is M1/((1p)(M2M1))M_1/((1-p)(M_2 - M_1))M1))M_1)). This is the minimum hazard ratio for decreasing hazards.

Author(s)

C. H. Jackson [email protected]

References

C. Dutang, V. Goulet and M. Pigeon (2008). actuar: An R Package for Actuarial Science. Journal of Statistical Software, vol. 25, no. 7, 1-37. URL http://www.jstatsoft.org/v25/i07


Update the maximum likelihood estimates in a fitted model object.

Description

Update the maximum likelihood estimates in a fitted model object. Intended for developer use only.

Usage

updatepars.msm(x, pars)

Arguments

x

A fitted multi-state model object, as returned by msm.

pars

Vector of new parameters, in their untransformed real-line parameterisations, to substitute for the maximum likelihood estimates corresponding to those in the estimates component of the fitted model object (msm.object). The order of the parameters is documented in msm, argument fixedpars.

Value

An updated msm model object with the updated maximum likelihood estimates, but with the covariances / standard errors unchanged.

Point estimates from output functions such as qmatrix.msm, pmatrix.msm, or any related function, can then be evaluated with the new parameters, and at arbitrary covariate values.

This function is used, for example, when computing confidence intervals from pmatrix.msm, and related functions, using the ci="normal" method.

Author(s)

C. H. Jackson [email protected]


Calculate the probabilities of underlying states and the most likely path through them

Description

For a fitted hidden Markov model, or a model with censored state observations, the Viterbi algorithm recursively constructs the path with the highest probability through the underlying states. The probability of each hidden state is also computed for hidden Markov models, using the forward-backward algorithm.

Usage

viterbi.msm(x, normboot = FALSE, newdata = NULL)

Arguments

x

A fitted hidden Markov multi-state model, or a model with censored state observations, as produced by msm

normboot

If TRUE, then before running the algorithm, the maximum likelihood estimates of the model parameters are replaced by an alternative set of parameters drawn randomly from the asymptotic multivariate normal distribution of the MLEs.

newdata

An optional data frame containing observations on which to construct the Viterbi path and forward-backward probabilities. It must be in the same format as the data frame used to fit x. If NULL, the data frame used to fit x is used.

Value

A data frame with columns:

subject = subject identification numbers

time = times of observations

observed = corresponding observed states

fitted = corresponding fitted states found by Viterbi recursion. If the model is not a hidden Markov model, and there are no censored state observations, this is just the observed states.

For hidden Markov models, an additional matrix pstate is also returned inside the data frame, giving the probability of each hidden state at each point, conditionally on all the data. This is computed by the forward/backward algorithm.

Author(s)

C. H. Jackson [email protected]

References

Durbin, R., Eddy, S., Krogh, A. and Mitchison, G. Biological sequence analysis, Cambridge University Press, 1998.

See Also

msm