---
title: "Maraca Plots - Alternative Endpoints"
author: "Monika Huhn"
date: "`r Sys.Date()`"
output: rmarkdown::html_vignette
vignette: >
  %\VignetteIndexEntry{Maraca Plots - Alternative Endpoints}
  %\VignetteEngine{knitr::rmarkdown}
  \usepackage[utf8]{inputenc}
---

```{r setup, include = FALSE}
knitr::opts_chunk$set(echo = TRUE, collapse = TRUE)
library(dplyr)
library(maraca)
```

The maraca package can also be used for hierarchical endpoints containing other type of endpoints than
time-to-event and continuous. Currently binary endpoints are also supported with further type of
endpoints under development


## Binary endpoints

### Last outcome

First we go through an example where the final outcome instead of being continuous, is a binary outcome.
As an example, this could for example be weight loss above a certain threshold at the end of the study.
The way the outcome should be included in the data is as a numeric vector with 1 for those patients that
had the outcome and 0 for those that had not.

We do not have any example dataset with a final binary endpoint included in the package, so for
this vignette we modify an existing dataset:

```{r}
data("hce_scenario_a")
# Create data with binary version of continuous final endpoint
bin_data <- hce_scenario_a
# Index of all continuous outcome rows 
idx_cont <- bin_data$GROUP == "Continuous outcome"
# Rename outcome
bin_data[idx_cont,"GROUP"] <- "Binary outcome"
# Binary version (>= 0/< 0)
bin_data[idx_cont,"AVAL0"] <- bin_data[idx_cont,"AVAL0"] >= 0
bin_data[idx_cont,"AVAL"] <- bin_data[idx_cont,"AVAL0"] +
  bin_data[idx_cont,"GROUPN"]
head(bin_data)
```

If we now want to create a maraca object for this data, we need to slightly update
the default code. By default, maraca expects the last outcome to be continuous. In
order for the function to know that the last outcome is binary, we have to update
the parameter `last_type`. The parameter currently accepts the inputs `"binary"` and
`"continuous"`.
```{r}
column_names <- c(
    outcome = "GROUP",
    arm = "TRTP",
    value = "AVAL0"
)

step_outcomes <- c("Outcome I", "Outcome II",
                   "Outcome III", "Outcome IV")

last_outcome <- "Binary outcome"

arm_levels <- c(active = "Active",
                control = "Control")

mar <- maraca(
  bin_data, step_outcomes, last_outcome,
  arm_levels, column_names,
  fixed_followup_days = 3*365,
  compute_win_odds = TRUE,
  # Important change: Add information that last endpoint is 
  # not continuous (the default)
  last_type = "binary"
)
```

The maraca object can now be plotted. A binary endpoint is plotted
as an ellipsis. The point in the middle of the ellipsis indicates the
proportion that has met the binary endpoint. The width of the ellipsis
(x-axis range) shows the confidence interval.
Specifying `vline_type = "mean"` (the default) will add vertical lines
indicating the proportions in each treatment group for easier readibility.
Note that `vline_type = "median"` (the default for continuous endpoints)
will result in an error. The same is true for setting `density_plot_type` to
anything other than `"default"`.
```{r fig.width = 7, fig.height = 6}
plot(mar)
```


### Step outcome

What if the binary outcome is not the last outcome of the hierarchical endpoint
but rather one (or several) of the previous outcomes? So rather than solely having
time-to-event endpoints within the step function part of the plot, we also have
at least one binary (so not time depending) variable.
To include a binary variable, we expect the data for this outcome to include only
patients that had the outcome and they all have to have the original analysis value 1.

Let's create a dataset with 2 binary outcomes.
```{r}
data("hce_scenario_a")
# Create data with binary version of continuous final endpoint
bin_data2 <- hce_scenario_a
# Index of all continuous outcome rows 
idx_bin <- bin_data2$GROUP %in% c("Outcome III", "Outcome IV")
# Binary version (>= 0/< 0), coded as 1
bin_data2[idx_bin,"AVAL0"] <- bin_data2[idx_bin,"AVAL0"] >= 500
bin_data2[idx_bin,"AVAL"] <- bin_data2[idx_bin,"AVAL0"] +
  bin_data2[idx_bin,"GROUPN"]
# Remove 0 rows (only include patients that had the outcome)
bin_data2 <- bin_data2[bin_data2$AVAL0 != 0,]
head(bin_data2)
```

Again we need to slightly update the default code if we want to create a maraca object
for this data. By default, maraca expects all the step outcomes to be time-to-event
endpoints.  In order for the function to know that there are binary outcomes, we have to
update the parameter `step_types`. The parameter currently accepts the inputs `"binary"` and
`"tte"`. If all the step outcomes are of the same type, the user can give the type as a string
(such as by default `step_types = "tte"`). If there are different endpoint types, then the user
has to provide a vector with one element for each step outcome.
Similarly, the fixed-follow up time can be given as a single number or a vector. Note that the
fixed-follow-up time is only needed for time-to-event endpoints, so if providing a vector then
it should contain one value for each time-to-event endpoint.
```{r}
column_names <- c(
    outcome = "GROUP",
    arm = "TRTP",
    value = "AVAL0"
)

step_outcomes <- c("Outcome I", "Outcome II",
                   "Outcome III", "Outcome IV")

last_outcome <- "Continuous outcome"

arm_levels <- c(active = "Active",
                control = "Control")

mar <- maraca(
  bin_data2, step_outcomes, last_outcome,
  arm_levels, column_names,
  fixed_followup_days = 3*365,
  compute_win_odds = TRUE,
  # Important change: Add information that last endpoint is 
  # not continuous (the default)
  step_types = c("tte","tte","binary","binary")
)
```

Again, we can plot the final object.
```{r fig.width = 7, fig.height = 6}
plot(mar)
```


As with all maraca objects, the different plotting parameters can be
used.

```{r fig.width = 7, fig.height = 6}
plot(mar, continuous_grid_spacing_x = 20,
     theme = "color1")
```

Also, the win odds plots can be created as usual.
```{r fig.width = 7, fig.height = 6}
component_plot(mar,
     theme = "color2")
```

```{r fig.width = 7, fig.height = 6}
cumulative_plot(mar,
     theme = "color1")
```