Help for package DTEAssurance

Type:

Package

Title:

Assurance Methods for Clinical Trials with a Delayed Treatment Effect

Version:

1.0.1

Description:

Provides functions for planning clinical trials subject to a delayed treatment effect using assurance-based methods. Includes two 'shiny' applications for interactive exploration, simulation, and visualisation of trial designs and outcomes. The methodology is described in: Salsbury JA, Oakley JE, Julious SA, Hampson LV (2024) "Assurance methods for designing a clinical trial with a delayed treatment effect" <doi:10.1002/sim.10136>, Salsbury JA, Oakley JE, Julious SA, Hampson LV (2024) "Adaptive clinical trial design with delayed treatment effects using elicited prior distributions" <doi:10.48550/arXiv.2509.07602>.

License:

MIT + file LICENSE

Encoding:

UTF-8

LazyData:

true

RoxygenNote:

7.3.3

Imports:

SHELF, shiny, stats, survival, nleqslv, nph, nphRCT, dplyr, rjags, rpact, magrittr, rlang, future.apply

Suggests:

testthat (≥ 3.0.0)

Config/testthat/edition:

Depends:

R (≥ 4.0)

Date:

2025-09-25

URL:

https://jamesalsbury.github.io/DTEAssurance/

NeedsCompilation:

Packaged:

2025-10-24 14:16:18 UTC; smp21js

Author:

James Salsbury

[aut, cre]

Maintainer:

James Salsbury <jsalsbury1@sheffield.ac.uk>

Repository:

CRAN

Date/Publication:

2025-10-24 14:30:02 UTC

Pipe operator

Description

See magrittr::%>% for details.

Usage

lhs %>% rhs

Arguments

lhs

A value or the magrittr placeholder.

rhs

A function call using the magrittr semantics.

Value

The result of calling rhs(lhs).

INTEREST data set

Description

A reconstructed survival data set for the INTEREST clinical trial

Usage

INTEREST

Format

A data frame with 710 rows and 2 variables:

Survival time: Survival Time (in months)
Status: Event indicator (0=Alive, 1=Dead)

Source

Reconstructed survival data set from the following publication: https://www.sciencedirect.com/science/article/pii/S0140673608617584?via%3Dihub

MCMC_sample

Description

An MCMC sample for the example given in Salsbury et al (2024)

Usage

MCMC_sample

Format

A data frame with 100000 rows and 1 variables:

x: Sample from the MAP prior

Source

A MCMC sample for the control group for the example given in https://onlinelibrary.wiley.com/doi/full/10.1002/sim.10136. Three historical data seta are used to generate a Meta-Analytic-Predictive Prior distribution

REVEL data set

Description

A reconstructed survival data set for the REVEL clinical trial

Usage

REVEL

Format

A data frame with 625 rows and 2 variables:

Survival time: Survival Time (in months)
Status: Event indicator (0=Alive, 1=Dead)

Source

Reconstructed survival data set from the following publication: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60845-X/fulltext

ZODIAC data set

Description

A reconstructed survival data set for the ZODIAC clinical trial

Usage

ZODIAC

Format

A data frame with 697 rows and 2 variables:

Survival time: Survival Time (in months)
Status: Event indicator (0=Alive, 1=Dead)

Source

Reconstructed survival data set from the following publication: https://www.sciencedirect.com/science/article/abs/pii/S1470204510701327?via%3Dihub

Add recruitment time to a survival dataset

Description

Simulates recruitment timing for each subject in a survival dataset using either a power model or a piecewise constant (PWC) model. The function appends recruitment times and pseudo survival times (time from recruitment to event or censoring).

Usage

add_recruitment_time(
  data,
  rec_method,
  rec_period = NULL,
  rec_power = NULL,
  rec_rate = NULL,
  rec_duration = NULL
)

Arguments

data

A dataframe containing survival data with columns: time, status, and group

rec_method

Recruitment method: "power" for power model or "PWC" for piecewise constant model

rec_period

Period length for the power model

rec_power

Power parameter for the power model

rec_rate

Comma-separated string of recruitment rates for the PWC model

rec_duration

Comma-separated string of durations corresponding to each rate in the PWC model

Value

A dataframe with two additional columns:

rec_time: Simulated recruitment time for each subject
pseudo_time: Time from recruitment to event or censoring

Class: data.frame

Examples

set.seed(123)
df <- data.frame(
  time = rexp(20, rate = 0.1),
  status = rbinom(20, 1, 0.8),
  group = rep(c("Control", "Treatment"), each = 10)
)
recruited <- add_recruitment_time(df, rec_method = "power", rec_period = 12, rec_power = 1)
head(recruited)

Launch the 'shiny' GSD Assurance app

Description

Launches a 'shiny' application to simulate group sequential trials with delayed treatment effects (DTE) using elicited prior distributions. The app allows interactive exploration of trial designs and assurance calculations.

Usage

assurance_GSD_shiny_app()

Value

No return value, called for side effects (invisibly returns NULL). The function launches an interactive 'shiny' application.

Examples

if (interactive()) {
  # Launch the interactive app in an R session
  assurance_GSD_shiny_app()
}

Launch the 'shiny' Assurance app

Description

Launches a 'shiny' application to calculate assurance for clinical trials where delayed treatment effects (DTE) may be present. The app allows elicitation of prior distributions and calculates assurance metrics.

Usage

assurance_shiny_app()

Value

No return value, called for side effects (invisibly returns NULL). The function launches an interactive 'shiny' application.

Examples

if (interactive()) {
  # Launch the interactive app in an R session
  assurance_shiny_app()
}

Calculate Assurance for a Trial with a Delayed Treatment Effect

Description

Simulates operating characteristics for a clinical trial under prior uncertainty about a delayed treatment effect. The function integrates beliefs about control survival, treatment delay, post-delay hazard ratio, recruitment, censoring, and analysis method to estimate assurance and other trial metrics.

Usage

calc_dte_assurance(
  n_c,
  n_t,
  control_model,
  effect_model,
  censoring_model,
  recruitment_model,
  analysis_model,
  n_sims = 1000
)

Arguments

n_c

Vector of control group sample sizes

n_t

Vector of treatment group sample sizes

control_model

A named list specifying the control arm survival distribution:

dist: Distribution type ("Exponential" or "Weibull")
parameter_mode: Either "Fixed" or "Distribution"
fixed_type: If "Fixed", specify as "Parameters" or "Landmark"
lambda, gamma: Scale and shape parameters
t1, t2: Landmark times
surv_t1, surv_t2: Survival probabilities at landmarks
t1_Beta_a, t1_Beta_b, diff_Beta_a, diff_Beta_b: Beta prior parameters

effect_model

A named list specifying beliefs about the treatment effect:

delay_SHELF, HR_SHELF: SHELF objects encoding beliefs
delay_dist, HR_dist: Distribution types ("hist" by default)
P_S: Probability that survival curves separate
P_DTE: Probability of delayed separation, conditional on separation

censoring_model

A named list specifying the censoring mechanism:

method: "Time", "Events", or "IF"
time, events, IF: Parameters for each method

recruitment_model

A named list specifying the recruitment process:

method: "power" or "PWC"
period, power: Parameters for power model
rate, duration: Comma-separated strings for PWC model

analysis_model

A named list specifying the statistical test and decision rule:

method: "LRT", "WLRT", or "MW"
alpha, alternative_hypothesis: Type I error and hypothesis direction
rho, gamma, t_star, s_star: Parameters for WLRT or MW
success_threshold_HR: Optional threshold for declaring success

n_sims

Number of simulations to run (default = 1000)

Value

A named list containing:

assurance: Estimated assurance (probability of success under prior uncertainty)
CI: 95% confidence interval for assurance
duration: Mean trial duration across simulations
sample_size: Mean sample size across simulations
diagnostics: Additional diagnostics if success_threshold_HR is specified

Class: list

Examples

# Minimal example with placeholder inputs
control_model <- list(dist = "Exponential", parameter_mode = "Fixed",
fixed_type = "Parameters", lambda = 0.1)
effect_model <- list(delay_SHELF = SHELF::fitdist(c(3, 4, 5),
probs = c(0.25, 0.5, 0.75), lower = 0, upper = 10),
delay_dist = "gamma",
HR_SHELF = SHELF::fitdist(c(0.55, 0.6, 0.7), probs = c(0.25, 0.5, 0.75), lower = 0, upper = 1.5),
HR_dist = "gamma",
P_S = 1, P_DTE = 0)
censoring_model <- list(method = "Time", time = 12)
recruitment_model <- list(method = "power", period = 12, power = 1)
analysis_model <- list(method = "LRT", alpha = 0.025, alternative_hypothesis = "two.sided")
result <- calc_dte_assurance(n_c = 300, n_t = 300,
                                     control_model = control_model,
                                     effect_model = effect_model,
                                     censoring_model = censoring_model,
                                     recruitment_model = recruitment_model,
                                     analysis_model = analysis_model,
                                     n_sims = 10)
str(result)

Calculates operating characteristics for a Group Sequential Trial with a Delayed Treatment Effect

Description

Simulates assurance and operating characteristics for a group sequential trial under prior uncertainty about a delayed treatment effect. The function integrates beliefs about control survival, treatment delay, post-delay hazard ratio, recruitment, and group sequential design (GSD) parameters.

Usage

calc_dte_assurance_interim(
  n_c,
  n_t,
  control_model,
  effect_model,
  recruitment_model,
  GSD_model,
  n_sims = 1000
)

Arguments

n_c

Control group sample size

n_t

Treatment group sample size

control_model

A named list specifying the control arm survival distribution:

dist: Distribution type ("Exponential" or "Weibull")
parameter_mode: Either "Fixed" or "Distribution"
fixed_type: If "Fixed", specify as "Parameters" or "Landmark"
lambda, gamma: Scale and shape parameters
t1, t2: Landmark times
surv_t1, surv_t2: Survival probabilities at landmarks
t1_Beta_a, t1_Beta_b, diff_Beta_a, diff_Beta_b: Beta prior parameters

effect_model

A named list specifying beliefs about the treatment effect:

delay_SHELF, HR_SHELF: SHELF objects encoding beliefs
delay_dist, HR_dist: Distribution types ("hist" by default)
P_S: Probability that survival curves separate
P_DTE: Probability of delayed separation, conditional on separation

recruitment_model

A named list specifying the recruitment process:

method: "power" or "PWC"
period, power: Parameters for power model
rate, duration: Comma-separated strings for PWC model

GSD_model

A named list specifying the group sequential design:

events: Total number of events
alpha_spending: Cumulative alpha spending vector
beta_spending: Cumulative beta spending vector
IF_vec: Vector of information fractions

n_sims

Number of simulations to run (default = 1000)

Value

A data frame with one row per simulated trial and the following columns:

Trial: Simulation index
IF: Information fraction label used at the decision point
Decision: Interim decision outcome (e.g., "Continue", "Stop for efficacy", "Stop for futility")
StopTime: Time at which the trial stopped or completed
SampleSize: Total sample size at the time of decision
Final_Decision: Final classification of trial success based on the test statistic and threshold

Class: data.frame

Examples

# Minimal example with placeholder inputs
control_model <- list(dist = "Exponential", parameter_mode = "Fixed",
fixed_type = "Parameters", lambda = 0.1)
effect_model <- list(P_S = 1, P_DTE = 0,
HR_SHELF = SHELF::fitdist(c(0.6, 0.65, 0.7), probs = c(0.25, 0.5, 0.75), lower = 0, upper = 2),
HR_dist = "gamma",
delay_SHELF = SHELF::fitdist(c(3, 4, 5), probs = c(0.25, 0.5, 0.75), lower = 0, upper = 10),
delay_dist = "gamma"
)
recruitment_model <- list(method = "power", period = 12, power = 1)
GSD_model <- list(events = 300, alpha_spending = c("0.01, 0.025"),
                  beta_spending = c("0.05, 0.1"), IF_vec = c("0.5, 1"))
result <- calc_dte_assurance_interim(n_c = 300, n_t = 300,
                        control_model = control_model,
                        effect_model = effect_model,
                        recruitment_model = recruitment_model,
                        GSD_model = GSD_model,
                        n_sims = 10)
str(result)

Censor a survival dataset

Description

Applies administrative censoring to a survival dataset using one of three methods: fixed time, fixed number of events, or fixed information fraction. The input data must contain columns for pseudo survival time, recruitment time, and observed time.

Usage

cens_data(
  data,
  cens_method = "Time",
  cens_time = NULL,
  cens_IF = NULL,
  cens_events = NULL
)

Arguments

data

A dataframe containing uncensored survival data with columns: pseudo_time, rec_time, and time

cens_method

Censoring method: "Time" (default), "Events", or "IF"

cens_time

Time point for censoring (required if cens_method = "Time")

cens_IF

Information fraction for censoring (required if cens_method = "IF")

cens_events

Number of events for censoring (required if cens_method = "Events")

Value

A list containing:

data: Censored dataframe with updated status and filtered rows
cens_events: Number of events used for censoring (if applicable)
cens_time: Time point used for censoring
sample_size: Number of subjects remaining after censoring

Examples

set.seed(123)
df <- data.frame(
  pseudo_time = rexp(20, rate = 0.1),
  rec_time = runif(20, 0, 12),
  time = rexp(20, rate = 0.1)
)
censored <- cens_data(df, cens_method = "Time", cens_time = 10)
str(censored)

Simulates survival times for a delayed treatment effect (DTE) scenario, where the treatment group experiences a delayed onset of benefit. Control and treatment groups are generated under exponential or Weibull distributions.

Description

Simulates survival times for a delayed treatment effect (DTE) scenario, where the treatment group experiences a delayed onset of benefit. Control and treatment groups are generated under exponential or Weibull distributions.

Usage

sim_dte(
  n_c,
  n_t,
  lambda_c,
  delay_time,
  post_delay_HR,
  dist = "Exponential",
  gamma_c = NULL
)

Arguments

n_c

The number of patients in the control group

n_t

The number of patients in the treatment group

lambda_c

The baseline hazard rate for the control group

delay_time

The length of delay before treatment effect begins

post_delay_HR

The hazard ratio after the delay period

dist

The distribution for the control group; must be one of "Exponential" (default) or "Weibull"

gamma_c

The shape parameter for the Weibull distribution (only used if dist = "Weibull")

Value

A data frame with two columns:

time

Simulated survival times

group

Group assignment: "Control" or "Treatment"

Class: data.frame

Examples

set.seed(123)
sim_data <- sim_dte(n_c = 10, n_t = 10, lambda_c = 0.1,
                    delay_time = 6, post_delay_HR = 0.6)
head(sim_data)

Calculate statistical significance on a survival dataset

Description

Performs a survival analysis using either the standard log-rank test (LRT) or a weighted log-rank test (WLRT). The function estimates the hazard ratio and determines whether the result is statistically significant based on the specified alpha level and alternative hypothesis.

Usage

survival_test(
  data,
  analysis_method = "LRT",
  alternative = "one.sided",
  alpha = 0.05,
  rho = 0,
  gamma = 0,
  t_star = NULL,
  s_star = NULL
)

Arguments

data

A dataframe containing survival data. Must include columns for survival time, event status, and treatment group.

analysis_method

Method of analysis: "LRT" (default) for standard log-rank test, or "WLRT" for weighted log-rank test.

alternative

String specifying the alternative hypothesis. Must be one of "one.sided" or "two.sided" (default).

alpha

Type I error threshold for significance testing.

rho

Rho parameter for the Fleming-Harrington weighted log-rank test.

gamma

Gamma parameter for the Fleming-Harrington weighted log-rank test.

t_star

Parameter t^* used in modestly weighted tests.

s_star

Parameter s^* used in modestly weighted tests.

Value

A list containing:

Signif: Logical indicator of statistical significance based on the chosen test and alpha level.
observed_HR: Estimated hazard ratio from a Cox proportional hazards model.

Examples

set.seed(123)
df <- data.frame(
  survival_time = rexp(40, rate = 0.1),
  status = rbinom(40, 1, 0.8),
  group = rep(c("Control", "Treatment"), each = 20)
)
result <- survival_test(df, analysis_method = "LRT", alpha = 0.05)
str(result)

Package imports

Description

Package imports