index.Rmd

---
title: "Closing the Gap"
subtitle: "Creating an End-to-End R Package Toolkit for the Clinical Reporting Pipeline"
author: "Eli Miller, Atorus & Ben Straub, GSK"
institute: "Phuse Connect 2022"
date: "04-May-2022"
output:
  xaringan::moon_reader:
    css: ['fc','fc-fonts', 'www/css/style.css']
    lib_dir: libs
    nature:
      highlightStyle: github
      titleSlideClass: ["bottom", "left"]
      slideNumberFormat: "%current%"
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      ratio: "16:9"

---

class: middle, center

# Objective

## Present and discuss three R packages: {metacore}, {logrx}, {xportr} and how they fit into the larger framework of the {pharmaverse} answer to the Clinical Reporting Pipeline.


```{r, echo=FALSE, out.width="25%"}
knitr::include_graphics("www/img/ctg.png")
```




---

class: middle, center

# Outline

<br/>

Defining the Clinical Reporting Pipeline

A collaboration begins between Atorus and GSK

Open Source in a Regulated Environment

Overview of the 3 Packages – {metacore}, {logrx}, {xportr}

Welcome to the {pharmaverse}!

---

# The Clinical Reporting Pipeline

.center[
```{r, echo = FALSE, results = 'asis'}
nomnoml::nomnoml(
  "[<frame>Focus on during/after the clinical trials|
  [Collected|
  CRFs
  Lab Assays
  PK
  Medical Coding
]

[Tabulation|
  SDTM
  Traceability
  No derivations
  Comprehensive
]

[Analysis Ready|
ADaM
\"One Proc Away\"
\"One %>% Away\"
Derived data
Traceability
] 

[Results|
Data Displays
Case Study Report
Submission Package
Quality Control
]

[Delivery to Agency|
eCTD Portal
]

[Collected] -> [Tabulation]
[Tabulation] -> [Analysis Ready]
[Analysis Ready] -> [Results]
[Results] -> [Delivery to Agency]
]",
width = 1000,
height = 500
)
```
]

---

![timeline](www/img/project_timeline.png)

---

# Challenges of using an Open-Source Language in a Regulated Environment

.two-column[

  .left-col[

  **An Incomplete List of Challenges** 

  - SAS® processes have years of use within regulatory agencies and tend to take precedence.   

  - Company Firewalls and VPNs.  

  - Sharing of code and data. 

  - Does a R package bend to SAS® processes or does the package recreate/redefine the process?

  - Who maintains the open-source product?

  ]

  .right-col[

  **An Incomplete List of Solutions**

  - Github, Gitlab and etc. help us to share, fix and build up code in an interactive and version-controlled process.

  - R Consortium is working with the FDA to investigate delivering a submission in R.

  - R packages already out there that mimic some of SAS® processes – {haven}, {SASxport}

  - Pharma companies will have a vested interest in maintaining these packages.
  
  - New graduates are coming out of school with R and Python skills

  ]

]



---

# Risk Mitigation: Why xportr pacakge is not on CRAN(yet)
.two-column[

.left-col[

### Backend dependancy issues

### Limited time from OS developers

### Difficulty Explaining the Need for Changes

]

.right-col[
- [Dec 11, 2020 - SASxport Issue Reported](https://github.com/r-gregmisc/SASxport/issues/20) 

- [Feb 5, 2021 - PR to SASxport merged in](https://github.com/r-gregmisc/SASxport/pull/21) 

- [Nov 17, 2021 - Issue with haven reported](https://github.com/tidyverse/haven/issues/650) 

- [Nov 23, 2021 - Fix in underlying haven library patched](https://github.com/WizardMac/ReadStat/pull/258) 

- [Feb 21, 2022 - New release for haven backend](https://github.com/WizardMac/ReadStat/releases/tag/v1.1.8-rc0)

- [Feb 25, 2022 - Backend updates made to haven](https://github.com/tidyverse/haven/pull/659) 

- [April 15, 2022 - Updates to haven released and have been implemented into xportr](https://github.com/tidyverse/haven/releases/tag/v2.5.0)

]
]

---

# {metacore}

.two-column[

.left-col[
![metacore](www/img/metacore.png)
]

.right-col[
**Challenges for R in CRP**

- No available R packages that can ingest and parse metadata for clinical trial datasets or help build a define.xml.

**Solutions**

- Built functions for parsing xml data and other data types specific to clinical trial datasets.

- Functions and objects can be leveraged to help for dataset and variable creation as well as user for creating and codelist and derivations.

**Future development path**

- Working with different company's metadata files as well as in-development packages, e.g., admiral, to leverage metadata upstream or downstream.
]

]



---

# {logrx}

.two-column[

.left-col[
![logrx](www/img/timber_May_2022.png)
]

.right-col[
**Challenges for R in CRP**

- There is no SAS-like log file for R-based programs that show traceability and help to create audit-ready code.

**Solutions**

- Created a utilities and wrapper functions to capture user info, session information and warnings and errors in an easy-to-read format.

- Allows for recreation of script, not just the output.

**Future development path**

- Interactive display screen to batch submit multiple programs.

- What else should go in a log?  Companies might have different needs.

- Name changed to logrx - got to be quick!!
]
]

---

class: middle, left

# {xportr}

![xportr](www/img/xportr_piped.png)


**Challenges for R in CRP**

- Writing a compliant xpt file using haven or other xpt-supported packages is challenging for types, lengths and labels

**Solutions**

- Adding well defined metadata
- Helps to write compliant xpt files
- Custom error, warnings and messages for information about metadata
- Checks on the data before final output

**Future development path**

- How to ingest metadata specifications from different companies and different file formats

---

# 

<iframe src='www/example.html' style="width:100%;height:85%;"/>

---

# 

<iframe src='www/example_with_log.html' style="width:100%;height:85%;"/>

---

# Welcome to the `{pharmaverse}`!

<img src="www/img/pharmaverse.png" style="width:100%;" />