MAMS (version 3.0.0)

tite.mams: Function to design multi-arm multi-stage studies with time-to-event endpoints

Description

The function determines (approximately) the boundaries of a multi-arm multi-stage study with time-to-event endpoints for a given boundary shape and finds the required number of events.

Usage

tite.mams(
  hr = 1.5,
  hr0 = 1.1,
  K = 4,
  J = 2,
  alpha = 0.05,
  power = 0.9,
  r = 1:2,
  r0 = 1:2,
  ushape = "obf",
  lshape = "fixed",
  ufix = NULL,
  lfix = 0,
  nstart = 1,
  nstop = NULL,
  sample.size = TRUE,
  Q = 20,
  parallel = TRUE,
  print = TRUE
)

Value

An object of the class MAMS containing the following components:

l

Lower boundary.

u

Upper boundary.

n

Sample size on control in stage 1.

N

Maximum total sample size.

K

Number of experimental treatments.

J

Number of stages in the trial.

alpha

Familywise error rate.

alpha.star

Cumulative familywise error rate spent by each analysis.

power

Power under least favorable configuration.

rMat

Matrix of allocation ratios. First row corresponds to control while subsequent rows are for the experimental treatments.

Arguments

hr

Interesting treatment effect on the scale of hazard ratios (default=2).

hr0

Uninteresting treatment effect on the scale of hazard ratios (default=1.2).

K

Number of experimental treatments (default=4).

J

Number of stages (default=2).

alpha

One-sided familywise error rate (default=0.05).

power

Desired power (default=0.9).

r

Vector of allocation ratios (default=1:2).

r0

Vector ratio on control (default=1:2).

ushape

Shape of upper boundary. Either a function specifying the shape or one of "pocock", "obf" (the default), "triangular" and "fixed".

lshape

Shape of lower boundary. Either a function specifying the shape or one of "pocock", "obf", "triangular" and "fixed" (the default).

ufix

Fixed upper boundary (default=NULL). Only used if shape="fixed".

lfix

Fixed lower boundary (default=0). Only used if shape="fixed".

nstart

Starting point for finding the sample size (default=1).

nstop

Stopping point for finding the sample size (default=NULL).

sample.size

Logical if sample size should be found as well (default=TRUE).

Q

Number of quadrature points per dimension in the outer integral (default=20).

parallel

if TRUE (default), allows parallelisation of the computation via a user-defined strategy specified by means of the function future::plan(). If not set differently, the default strategy is sequential, which corresponds to a computation without parallelisation.

print

if TRUE (default), indicate at which stage the computation is.

Author

Philip Pallmann, Dominic Magirr

Details

This function finds the (approximate) boundaries and sample size of a multi-arm multi-stage study with time-to-event endpoints with K active treatments plus control in which all promising treatments are continued at interim analyses as described in Magirr et al (2012). It is a wrapper around the basic mams function to facilitate its use with time-to-event endpoints, following ideas of Jaki & Magirr (2013). Note that the sample size is calculated as the required number of events, from which the total sample size can be estimated (e.g., Whitehead 2001). See ?mams for further details on the basic methodology.

Examples

# \donttest{
## An example 2-stage design with triangular efficacy and futility boundaries
tite.mams(hr=2, hr0=1.5, K=3, J=2, alpha=0.05, power=0.9,
          r=1:2, r0=1:2, ushape="triangular", lshape="triangular")
# }