knitr::opts_chunk$set( collapse = TRUE, comment = "#>" ) old <- options("digits" = 3) data.table::setDTthreads(2)

This package implements methods to analyse a sequence of target trials.

The steps to do this are:

- create a data set with all the required variables
- fit models for censoring and calculate inverse probability weights
- expand the data set, with records for each eligible patient for each trial period
- fit models for outcomes

The package provides two options for conducting the analysis: an all-in-one function and a set of more flexible functions.

To get started a longitudinal dataset must be created containing:

- time period
- patient identifier
- treatment indicator
- outcome indicator
- censoring indicator
- eligibility indicator for a trial starting in each time period
- other covariates relating to treatment, outcome, or informative censoring to be used in the models for weights or the outcome

An example data set is included to demonstrate the format:

library(TrialEmulation) # Prepare the example data data("trial_example") # Set columns to factors as necessary trial_example$catvarA <- as.factor(trial_example$catvarA) trial_example$catvarB <- as.factor(trial_example$catvarB) head(trial_example)

There is an all-in-one function `initators()`

which does all of the steps with one function call.
This is similar to the INITIATORS SAS macro.

Call the `initiators()`

function to run the complete analysis:

result <- initiators( data = trial_example, id = "id", period = "period", eligible = "eligible", treatment = "treatment", estimand_type = "ITT", outcome = "outcome", model_var = "assigned_treatment", outcome_cov = c("catvarA", "catvarB", "nvarA", "nvarB", "nvarC"), use_censor_weights = FALSE )

```
summary(result)
```

By default, this returns the final `glm`

model object and the results using the sandwich estimator.

summary(result$model)

Tidy summaries of the robust models are available.

print(result$robust$summary)

Also the sandwich robust variance-covariance matrix.

# only print the first columns head(result$robust$matrix, c(17, 4))

To gain complete control over the analysis and to inspect the intermediate objects, it can be useful to run the the data preparation and modelling steps separately.

This also allows for processing of very large data sets, by doing the data preparation in chunks and then sampling from the expanded trial data.

# for the purposes of the vignette, we use a temporary directory, however it may be useful to use a permanent # location in order to inspect the outputs later working_dir <- file.path(tempdir(TRUE), "trial_emu") if (!dir.exists(working_dir)) dir.create(working_dir)

prep_data <- data_preparation( data = trial_example, id = "id", period = "period", eligible = "eligible", treatment = "treatment", outcome = "outcome", outcome_cov = ~ catvarA + catvarB + nvarA + nvarB + nvarC, data_dir = working_dir, save_weight_models = TRUE, estimand_type = "PP", pool_cense = "none", use_censor_weights = FALSE, chunk_size = 500, separate_files = TRUE, switch_n_cov = ~ nvarA + nvarB, quiet = TRUE )

Use `summary`

to get an overview of the result.

```
summary(prep_data)
```

For more information about the weighting models, we can inspect them individually

prep_data$switch_models$switch_n0

If `save_weight_models = TRUE,`

the full model objects are saved in `working_dir`

, so you can inspect the data used in
those models and further investigate how well those models fit.

list.files(working_dir, "*.rds") # The path is stored in the saved object switch_n0 <- readRDS(prep_data$switch_models$switch_n0$path) summary(switch_n0) hist(switch_n0$fitted.values, main = "Histogram of weights from model switch_n0")

We also see the expanded trial files:

head(prep_data$data)

Each of these csv files contains the data for the trial starting at period `_i`

.
To create a manageable dataset for the final analysis we can sample from these trials.

Here we sample 10% of the patients without an event at each follow-up time in each trial. All observations with events are included.

sampled_data <- case_control_sampling_trials(prep_data, p_control = 0.1) str(sampled_data)

Before proceeding with the modelling, it is possible to manipulate and derive new variables and adjust factor levels
in the `data.frame`

. You can also specify transformations in a formula to `outcome_cov`

,
`include_followup_time`

or `include_trial_period`

, such as `~ ns(trial_period)`

or
`~ I(nvarA^2) + nvarC > 50 + catvarA:nvarC`

.

It is also possible to specify formulas in `trial_msm()`

to include, for example, splines with
`ns()`

.

Now we can fit the model with the `trial_msm()`

function. Since we have sampled from the data,
we should make use of the `use_sample_weights`

option to get correct survival estimates.

model_result <- trial_msm( data = sampled_data, outcome_cov = c("catvarA", "catvarB", "nvarA", "nvarB", "nvarC"), model_var = "assigned_treatment", glm_function = "glm", use_sample_weights = TRUE )

The result is the same type as the previous result from the simple `initiators`

function,
containing the `glm`

object and the sandwich results.

```
summary(model_result)
```

summary(model_result$model)

We can also use this object to predict cumulative incidence curves and use these for treatment comparisons.
Here we use the patients who were in the first trial as the target population. To get the data in the right format,
we can use the `data_template`

returned by `data_preparation()`

.

new_data <- data.table::fread(file.path(working_dir, "trial_1.csv")) new_data <- rbind(data.table::as.data.table(prep_data$data_template), new_data) model_preds <- predict(model_result, predict_times = c(0:40), newdata = new_data, type = "cum_inc")

The `predict`

function returns a list of 3 data frames: predictions for assigned treatment 0, for assigned treatment 1
and for the difference. It possible to change the type of predicted values, either cumulative incidence or survival.

plot( model_preds$difference$followup_time, model_preds$difference$cum_inc_diff, ty = "l", ylab = "Cumulative Incidence Difference", xlab = "Follow-up Time", ylim = c(-0.15, 0.05) ) lines(model_preds$difference$followup_time, model_preds$difference$`2.5%`, lty = 2) lines(model_preds$difference$followup_time, model_preds$difference$`97.5%`, lty = 2)

# clean up unlink(working_dir, recursive = TRUE)

options(old) data.table::setDTthreads(NULL)

**Any scripts or data that you put into this service are public.**

Embedding an R snippet on your website

Add the following code to your website.

For more information on customizing the embed code, read Embedding Snippets.