---
title: "secuTrialR - a walkthrough"
author: "Patrick R. Wright, Milica Markovic, Alan G. Haynes"
date: "`r Sys.Date()`"
output: rmarkdown::pdf_document
toc: true
vignette: >
  %\VignetteIndexEntry{secuTrialR-package-vignette}
  %\VignetteEngine{knitr::rmarkdown}
  %\VignetteEncoding{UTF-8}
---

\newpage

# Introduction

> “If I had just five minutes to chop down a tree I would spend the first two and a half minutes sharpening my axe.”

> `r tufte::quote_footer('--- An anonymous woodsman')`

\vspace{13pt}

This R package provides functions for handling data from the clinical data management system (CDMS) 
[\textcolor{blue}{secuTrial}](https://www.secutrial.com/en/).
The most important components are related to reading data exports from
secuTrial into R. In brief, the package aims to enable swift execution of
repetitive tasks in order to allow spending more time on the unique aspects
of a dataset. It is developed and maintained by the Swiss Clinical Trial Organisation
([\textcolor{blue}{SCTO}](https://www.scto.ch/en/news.html)).

If you are still challenged by more basic operations in R we suggest reading
[\textcolor{blue}{Hands-On Programming with R}](https://rstudio-education.github.io/hopr/),
which serves as an excellent introduction to the basic concepts of R.

This vignette will teach you how to use the `secuTrialR` package and you will likely
learn quite a bit about secuTrial exports in general along the way.
Throughout the `secuTrialR` package and within this vignette we refer to
patients, cases, subjects etc. enrolled in a secuTrial database as participants.

```{r, include = FALSE}
# needed so that the as.data.frame part of the vignette
# does not need a restart of the session everytime the
# vignette is built
#rm(list = ls()) # removed this at the request of the CRAN submission
knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>"
)
```

# Install

Please note that `R versions >= 3.5` should be used to run `secuTrialR`.
\vspace{5pt}

**Stable release from CRAN**
\vspace{5pt}
```{r, eval = FALSE}
install.packages("secuTrialR", dependencies = TRUE)
```

**Development release from GitHub with `devtools`**

For this you will need to have `devtools` installed.
If you are working on Windows and would like to install with `devtools` you
will likely need to install
[\textcolor{blue}{Rtools}](https://cran.r-project.org/bin/windows/Rtools/).
Installing everything, including the dependencies, from scratch may take a while (20-30 minutes).

\vspace{5pt}

```{r, eval = FALSE}
# install
devtools::install_github("SwissClinicalTrialOrganisation/secuTrialR")
```

```{r}
# load silently
suppressMessages(library(secuTrialR))
# show secuTrialR version
packageVersion("secuTrialR")
```

# The CTU05 dataset

Before we continue with the functionalities let's briefly talk about the test data which is
delivered as a part of the package. We refer to it as the `CTU05` (clinical trial unit project 05)
data. This dataset has been fabricated for demonstration purposes only and is not
real clinical data. Principally it is made up of eight forms. These are called "surgeries",
"baseline", "outcome", "treatment", "allmedi", "studyterminat", "ae" and "sae".
You will see these names again later when the data has been read into R.
The project setup includes most data types implementable in secuTrial. It is, however,
not exhaustive. Since the data is delivered with the installation of the `secuTrialR`
package we can point to it via the `system.file()` function.
\vspace{5pt}

```{r}
ctu05_data_location <- system.file("extdata", "sT_exports", "exp_opt",
                                   "s_export_CSV-xls_CTU05_all_info.zip",
                                   package = "secuTrialR")
```

If you work on your own datasets you can specify a path as a regular character string without
using `system.file()`.

# secuTrial export options

Prior to reading your data into R you need to export it with the secuTrial ExportSearchTool.
We suggest exporting **non-rectangular**, **zipped**, **English** data with 
**reference values** stored **in a separate table** including 
**Add-IDs**, **centre information**, **structure information**,  **form status**,
**project setup**, **without duplicated meta data** and **without form data of hidden fields**.
Furthermore, it is important to use
**"CSV format"**/**"CSV format for MS Excel"** and suggested to select **UTF-8** encoding.
Most of these options are truly optional and reading your data should
work even with differences from the above specifications.

A description of how data can be exported from secuTrial can be found
[\textcolor{blue}{here}](https://swissclinicaltrialorganisation.github.io/secuTrial_recipes/export_data/).
This description includes screenshots of the export options configuration interface.

# Reading a secuTrial data export into R

There is one principle function to read your data (i.e. `read_secuTrial()`).
Below you can see it in action with the `CTU05` dataset.
\vspace{5pt}

```{r}
ctu05_data <- read_secuTrial(data_dir = ctu05_data_location)
```

If the "Read export successfully." message appears your data was correctly read.
In this example you are also warned that hidden data fields are in the export which is a deviation
from the suggested export option configuraion.

# The `secuTrialdata` object

If you inspect the `class()` of `ctu05_data` you will find that it is a `secuTrialdata` object.
\vspace{5pt}

```{r}
class(ctu05_data)
```

Really this is only a `list` containing all the information from your secuTrial export.
\vspace{5pt}

```{r}
typeof(ctu05_data)
```

\newpage

## The data tables in the `secuTrialdata` object

We have implemented a custom variation of the `print()` function for `secuTrialdata` objects.

```{r}
print(ctu05_data)
```

It shows you where the export archive of your `secuTrialdata` object is located, tells you which
data tables (i.e. `table`) it contains, what the source files (i.e. `original_name`) are and
specifies each table's dimensions (i.e. `ncol`, `nrow`).

By now you have possibly realized that all the forms specified earlier
(i.e. "surgeries", "baseline", "outcome", "treatment", "allmedi", "studyterminat", "ae"
and "sae") are present, but also that there are many tables that do not correspond to the
previously introduced forms.

The majority of the unfamiliar tables are tagged as `TRUE` in the `meta` column.
This means that they are metadata tables. Their names and data structures
are fixed in secuTrial exports. In the following we will briefly explain
which information the most relevant meta tables contain.

* `vp` - visitplan definition
* `vpfs` - visitplan form linkage
* `fs` - forms information
* `qs` - questions
* `is` - items i.e. variable definitions
* `ctr` - centre information
* `cn` - casenodes i.e. table of entered study participants
* `cl` - information how the data in the variables is coded

Furthermore, there is a set of tables whose names start with "at". These are
audit trail tables. They are only relevant if you need to investigate changes
in the data over time. For example certain values may be corrected (i.e. changed)
due to findings during monitoring visits at study centres.
Last but not least you may have also realized that the "surgeries" table is
called `esurgeries`. This is because it is a so-called repetition form.
Repetition forms are labelled with a leading "e" and are implemented
as subforms in other forms. In this case, `esurgeries` is a subform in
`baseline` and the linkage is defined by the `mnpdocid` column in both tables.
If this sounds cryptic to you we suggest you talk so someone who has implemented
a database in secuTrial and let them explain it with a specific example.
It is pretty straight forward when you look at a concrete implementation.

## Accessing the tables and values

Since the `secuTrialdata` object is a `list` and the data tables within this `list` are
`data.frame`s you can simply access the tables using `$`. Let's say you would like to have
a look at the placebo to verum ratio in your `treatment` data or what types of other
medication were entered in `allmedi`.
\vspace{5pt}

```{r}
table(ctu05_data$treatment$rando_treatment)
table(ctu05_data$allmedi$med_product)
```

## Data transformations

During the loading process, coded categorical data is transformed. For example
the `gender` variable in the `baseline` form is categorical. The raw data is
accessible via `gender` and the transformed version of the data is added during
the reading process and becomes accessible via `gender.factor`. Thus, data is not overwritten
but added with the `.factor` extension. If there are issues during factorization
a `warning()` will inform you of this.
\vspace{5pt}

```{r}
# raw gender data
ctu05_data$baseline$gender

# transformed gender data
ctu05_data$baseline$gender.factor

# raw more meds
ctu05_data$allmedi$no_more_meds

# transformed more meds
ctu05_data$allmedi$no_more_meds.factor
```

Note that descriptive labels have also been automatically added to the data.
\vspace{5pt}

```{r}
label(ctu05_data$allmedi$no_more_meds.factor)
label(ctu05_data$baseline$gender.factor)
label(ctu05_data$esurgeries$surgery_organ.factor)
```

Datetime data is also transformed and similarly to the factorization
process the names are concatenated with
`.date` or `.datetime`.
\vspace{5pt}

```{r}
# raw
ctu05_data$baseline$visit_date

# processed
ctu05_data$baseline$visit_date.date

# raw only head
head(ctu05_data$baseline$hiv_date)

# processed only head
head(ctu05_data$baseline$hiv_date.datetime)

# classes
class(ctu05_data$baseline$visit_date)
class(ctu05_data$baseline$visit_date.date)
class(ctu05_data$baseline$hiv_date)
class(ctu05_data$baseline$hiv_date.datetime)

```

Depending on the setup, incomplete dates can be valid entries in a secuTrial database.
Thus they will also occasionally appear in your exports. The datetime conversion
does not work in these cases and `NA`s are created. If this happens, `secuTrialR` will
warn you accordingly and you should have a closer look into the affected
datetime variables and whether you would like to perform so-called date imputation.

## Export options

The `secuTrialdata` object also contains information on the export options.
\vspace{5pt}

```{r}
ctu05_data$export_options
```

`export_options` itself is a `list`. If you are interested in more information
than is printed you can also access it. Let's assume you would like to know
the `project_name` and `encoding`.
\vspace{5pt}

```{r}
ctu05_data$export_options$project_name
ctu05_data$export_options$encoding
```

Much more information is stored in the elements of `export_options`.
The names of the elements should be descriptive enough to infer the contents.
\vspace{5pt}

```{r}
names(ctu05_data$export_options)
```

# Generic functions for `secuTrialdata` objects

Now that you understand the `secuTrialdata` object we will show you some generic functions
you can use on objects of this class.

## Show the study participants

First off you may be interested in a table of participants.
\vspace{5pt}

```{r}
get_participants(ctu05_data)
```

Please note that the `mnpaid` column in this table corresponds to the `pat_id`
column in other tables.

\newpage

## Recruitment over time

You can extract information about participant recruitment per centre and year by applying
`annual_recruitment()` on a `secuTrialdata` object.
\vspace{5pt}

```{r}
annual_recruitment(ctu05_data)
```

Since the centre names often have a systematic addition (e.g. (RPACK)) we have
enabled the option to remove certain parts of the centre descriptions via
regular expressions (i.e. `rm_regex` argument). In this case the regular expression
removes trailing parentheses and everything they enclose.
\vspace{5pt}

```{r}
annual_recruitment(ctu05_data, rm_regex = "\\(.*\\)$")
```

It is also possible to plot the recruitment over time.
\vspace{5pt}

```{r, fig.height = 3.6, fig.width = 8}
plot_recruitment(ctu05_data, cex = 1.2, rm_regex = "\\(.*\\)$")
```

\newpage

## Visit plan visualization

`secuTrialR` can provide a depiction of the visit structure, although only where
the visit plan is fixed. Black rectangles in the grid represent a form to be filled (x)
during one of the visits (y).
\vspace{5pt}

```{r, fig.height = 3.9, fig.width = 3.9}
vs <- visit_structure(ctu05_data)
plot(vs)
```

## Completeness of forms

If you are not sure about how complete the data in your export is, it may be useful to
get a quick overview of how well the forms have been filled. The below table shows
both absolute and relative numbers for a few forms.
\vspace{5pt}

```{r}
fss <- form_status_summary(ctu05_data)
tail(fss, n = 5)
```

Please note that a form is only complete if all required fields have been filled.
Thus, a whole study may have 99% completeness on variable basis while showing
0% completeness on form basis. It is currently not technically possible to assess
completeness on variable basis in a generic way. Hence, high completeness on form
basis implies high completeness on variable basis but **NOT** vice versa.

If you would rather retrieve information on form completeness for each participant individually
you can perform the following.
\vspace{5pt}

```{r}
fsc <- form_status_counts(ctu05_data)
# show the top
head(fsc)
```

## Form linkage

Linkages amongst forms can be explored with the `links_secuTrial()` function.
This relies on the `igraph` package to create a network. It is possible to
interact with the network, e.g. move nodes around in order to read the labels better.
The R graphics device ID is returned to the console, but can be ignored. Forms are plotted in
deep yellow, variables in light blue.
\vspace{5pt}

```{r, eval = FALSE}
links_secuTrial(ctu05_data)
```

The output can not be shown within this vignette but you should give it a try.
Please note that the linkage plot is likely most useful **without** the audit trail
data in the export.

\newpage

## Sampling random participants

During study monitoring it is common practice to check random participants
from a study database. These participants should be retrieved in a reproducible
fashion, which can be achieved by setting a so-called seed.
The below function allows reproducible retrieval for a loaded secuTrial data export.
\vspace{5pt}

```{r}
# randomly retrieve at least 25 percent of participants recorded after March 18th 2019
# from the centres "Inselspital Bern" and "Charité Berlin"
return_random_participants(ctu05_data,
                           percent = 0.25,
                           seed = 1337,
                           date = "2019-03-18",
                           centres = c("Inselspital Bern (RPACK)",
                                       "Charité Berlin (RPACK)"))
```

Please note that earlier R versions may return different results because
there is a different `rng_config` (i.e. `RNGkind()`).
For this reason we have added the `rng_config` to the output.

## Retrieve score variables

secuTrial allows implementing calculated variables (i.e. scores). Data is
not directly entered into these variables but rather calculated automatically.
Scores are defined by a set of rules and use the data in other variables
as basis. For example the age of a study participant at data entry can be
calculated as the difference between the participant's birthday and the day
of data entry.

It is advisable to recalculate or validate score variable data before data analysis.
A rule of thumb: The more complex a score is and the more data from different 
forms is necessary for its calculation the more likely its value should be recalculated.
The below function will allow you to detect which variables this concerns.
\vspace{5pt}

```{r}
return_scores(ctu05_data)
```

## Retrieve hidden variables

Sometimes, during a study, certain fields may be hidden because data should
no longer be entered into them. If this is the case and the data of these
fields is part of your export is likely good to know about it. In this case
nothing is hidden.
\vspace{5pt}

```{r}
return_hidden_items(ctu05_data)
```


## Finding changes/differences in project setup implementations

In ongoing studies it is possible that changes to the secuTrial data entry
interface (i.e. the electronic case report forms) are made. Sometimes these
changes may call for adjustments in analysis code. It is considered good practice
to run `diff_secuTrial()` on the last export and the current export of a project
to at least make yourself aware of potential changes in the setup. If there are
differences, the results of this function should be interpreted as a first indicator
since they may not cover all alterations. Information is returned on forms and
variables. A detailed list of changes can be produced in the secuTrial
FormBuilder with "Compare project setup".

For the below `diff_secuTrial()` showcase we emulated a changed setup of CTU05
by copying the setup and importing it in the FormBuilder as a new secuTrial
project (CTU06). From this, we created a data export (v1) and then made a few
minor changes and exported again (v2). If this sounds confusing, never mind.
CTU06 v1 is simply a copy of CTU05. CTU06 v2 is a slighly altered version of CTU06 v1.
\vspace{5pt}

``` {r}
ctu06_v1 <- read_secuTrial(system.file("extdata", "sT_exports", "change_tracking",
                                       "s_export_CSV-xls_CTU06_version1.zip",
                                       package = "secuTrialR"))

ctu06_v2 <- read_secuTrial(system.file("extdata", "sT_exports", "change_tracking",
                                       "s_export_CSV-xls_CTU06_version2.zip",
                                       package = "secuTrialR"))

diff_secuTrial(ctu06_v1, ctu06_v2)

```

As you can see `ctu06_v2` contains the two additional forms `mnpctu06anewform` and
`mnpctu06anothernewform` and the two additional variables `new_item_in_fu` and
`new_item_in_new_form`.

## Conversion to SPSS, STATA, SAS

Given that you are working with R it is unlikely that you need such conversions for
yourself. However, collaborators may ask for data which is readily importable into SPSS,
STATA or SAS. For this you can use `write_secuTrial()`.  

Since this has not been heavily tested or used there may be issues and
you might prefer doing this manually with the `haven` package. One particular 
sticking point is the length of variable names - R is not restrictive in this 
respect, but other software can be. `secuTrialR` does not truncate names, prefering 
to leave this to the user, which can cause `write_secuTrial()` to fail with an error.
\vspace{5pt}

```{r, eval = FALSE}
# retrieve path to a temporary directory
tdir <- tempdir()
# write spss
write_secuTrial(ctu05_data, format = "sav", path = tdir)
```

## Subsetting `secuTrialdata`

In some cases it may be useful to subset your `secuTrialdata` object.
For example if you have cohort data and would like to supply a subset of
the data for a retrospective study. We have implemented this
option with `subset_secuTrial()`. It will truncate your `secuTrialdata` object
and return a new `secuTrialdata` object which is a subset of the original data.
It is possible to subset by including or excluding specific participant
ids or centres.
\vspace{5pt}

```{r}
# initialize some subset identifiers
participants <- c("RPACK-INS-011", "RPACK-INS-014", "RPACK-INS-015")
centres <- c("Inselspital Bern (RPACK)", "Universitätsspital Basel (RPACK)")

# exclude Bern and Basel
ctu05_data_berlin <- subset_secuTrial(ctu05_data, centre = centres, exclude = TRUE)
# exclude Berlin
ctu05_data_bern_basel <- subset_secuTrial(ctu05_data, centre = centres)
# keep only subset of participants
ctu05_data_pids <- subset_secuTrial(ctu05_data, participant = participants)

class(ctu05_data_berlin)
class(ctu05_data_bern_basel)
class(ctu05_data_pids)
```

If you subset based on centres all traces of deleted centres will be removed.
If you remove based on participant ids all traces of deleted participants will be removed.
\vspace{5pt}

```{r}
# only Berlin remains
ctu05_data_berlin$ctr

# all centres remain even though all three participant ids are from Bern
ctu05_data_pids$ctr
```

\newpage

Since the truncated object's class remains unchanged (i.e. `secuTrialdata`) you can
still use the generic functions on it.
Let's say you would only like to look at the recruitment plot for Bern alone.
\vspace{5pt}

```{r, fig.height = 3.8, fig.width = 8}
# keep only Bern
ctu05_data_bern <- subset_secuTrial(ctu05_data, centre = "Inselspital Bern (RPACK)")
# plot
plot_recruitment(ctu05_data_bern)
```

... or Bern and Berlin.
\vspace{5pt}

```{r, fig.height = 3.8, fig.width = 8}
# keep only Bern and Berlin
ctu05_data_bern_berlin <- subset_secuTrial(ctu05_data,
                                           centre = c("Inselspital Bern (RPACK)",
                                                      "Charité Berlin (RPACK)"))
# plot
plot_recruitment(ctu05_data_bern_berlin)
```

# Building URLs to your secuTrial server

If you are creating reports in which you would like to directly
link to specific pages of your secuTrial DataCapture you can
use `build_secuTrial_url`. If you are no expert regarding the
secuTrial server architecture you would like to build links for, you should
talk to the server admin or consult the `build_secuTrial_url` help page.
They will be able to guide you regarding the information for the `server`,
`instance`, `customer` and `project` parameters. The `docid`, however, is
included in your export data in the non-meta data tables of the
`secuTrialdata` object and can be found in the `mnpdocid` columns.

```{r}
head(ctu05_data$treatment$mnpdocid)
head(ctu05_data$baseline$mnpdocid)
```

To demsonstrate `build_secuTrial_url` we will use imaginary data
for the `server`, `instance`, `customer` and `project` parameters.
The real counterparts on your server will likely look structurally
similar.

```{r}
server <- "server.secutrial.com"
instance <- "ST21-setup-DataCapture"
customer <- "TES"
project <- "7036"

# make three links with the first three baseline docids
bl_docids <- head(ctu05_data$baseline$mnpdocid, n = 3)
links <- build_secuTrial_url(server, instance, customer,
                             project, bl_docids)
```
**These are the links**:  
`r links[1]`  

`r links[2]`  

`r links[3]`  

Of course they are dead ends but maybe you can use them to make
out the arguments for your server.

# The `as.data.frame` function

This vignette has been working with the `secuTrialdata` object, which is of type `list`.
For some users, working with a `list` can be tiresome so `secuTrialR` provides an
`as.data.frame()` method to save the `data.frame`s in the `secuTrialdata` object to
an environment of your choice.

As an example, we will create an environment called `env` and check that it's empty
before running `as.data.frame()`...
\vspace{5pt}

```{r}
env <- new.env()
ls(env)
```

```{r}
# add files to env
as.data.frame(ctu05_data, envir = env)
```

... and afterwards.
\vspace{5pt}
```{r}
ls(env)
```

Substituting `env` with `.GlobalEnv` instead would also be an option and would make the data.frames immediately accessible without having to refer to an environment.

# Frequent warning messages

Certain `warning` messages can occur quite frequently when running `read_secuTrial()`.
Some of them may call for deliberate action and thus it is important to understand them.
We briefly mentioned some of them earlier in this document but will now more closely
explain how they can be interpreted.

Please note that `warning` messages may "pile up" depending on the export you are reading.
For example this may happen if there are many date variables with incomplete data. This is
no reason for concern. We suggest that you read them and interpret them based on the
explanations below. We use `a_form_name` and `a_variable_name` as place holders in the examples.
If in doubt you can always work with the raw data because it is never overwritten.

## Dates

The below warning tells you that some data in a date variable could not be converted
during the process of date conversion (i.e. `dates_secuTrial()`). This ususally occurs
if incomplete date entries are present. Since the raw data is not overwritten but rather a
`variable_name.date` or `variable_name.datetime` column are added to the dataset you can specifically see which
values could not be converted because the raw data will contain data while the corresponding `.date`/`.datetime`
entires will be `NA`. The `warning` also indicates where to look. The dummy example below indicates to look
at the variable `a_variable_name` in form `a_form_name`.

```{r, echo = FALSE, results = TRUE}

# incomplete dates
warning(
"In dates_secuTrial.data.frame(tmp, datevars, timevars, dateformat,  :
Not all dates were converted for
variable: 'a_variable_name'
in form: 'a_form_name'
This is likely due to incomplete date entries."
)

```

## Factors

In some cases secuTrial allows differently coded data to be decoded to the same target value for the
same variable. For instance this can happen if hierarchical lookuptables have been implemented
in the database. Because this interferes with the factorization (i.e. `factorize_secuTrial()`)
we add the code to the duplicate decoded value and return the below message to make you aware.

If you run into this `warning` message we suggest running the `table()` function on the
variable in question. This will likely clarify the above explanation.

```{r, echo = FALSE, results = TRUE}
# duplicate factors
warning(
"In factorize_secuTrial.data.frame(curr_form_data, cl = object$cl,  :
Duplicate values found during factorization of a_variable_name")
```

## Labels

Sometimes the labels of variables in a secuTrial database implementation may be changed
after release of the database. In these cases all labels (current and previous versions) are
added to the `label` attribute during labelling (i.e. `label_secuTrial()`) and the below `warning`
is triggered. It indicates which variables in which forms are affected.

```{r, echo = FALSE, results = TRUE}
# duplicate labels
warning(
"In label_secuTrial.secuTrialdata(d) :
The labels attribute may be longer than 1 for the following variables and forms.
Likely the label was changed from its original state in the secuTrial project setup.
variables: a_variable_name
forms: a_form_name"
)
```

# A note on `mnp*` variables

There is a plethora of variables in the tables of secuTrial exports whose names start
with `mnp`. These are metadata variables which are e.g. important to logically link the
different tables. Explaining them all is beyond the scope of this vignette.
For detailed explanations, please refer to the secuTrial "Export Formats" user manual.

# Disclaimer
The descriptions of the secuTrial exports used in this vignette and other `secuTrialR`
documentation correspond to our understanding of them and come with no warranty.
For in depth details please refer to the original secuTrial manuals.

\newpage

```{r}
sessionInfo()
```


