Adapting OpenClinica for
International Collaborations
Andy Lin
University of Michigan
June 21, 2013
OpenClinica Global Conference 2013
Overview
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Background
Optical mark recognition
OpenClinica on bootable USB drive
Embedding audio files into OpenClinica CRFs
OpenClinica on iPad mini
Background
• UMHS-PUHSC Joint Institute
– Collaboration between University of Michigan
Health System and Peking University Health
Science Center
– Started in October 2010 to support collaborative
clinical and translational research
– Studies conducted jointly by teams at each
university
Joint Institute Structure
BRBI Core
• Biorepository and Biomedical Informatics
• Set up technological infrastructure for
supporting research data collection
• Establish standardized process for securing
and storing biological specimens and clinical
data
• Facilitates information sharing and data
management
Research Data Collection
• Selected OpenClinica after comparison with other
solutions
– Using Enterprise Edition in at UM, run by MICHR
– Using Community Edition in China
• Enterprise Edition not available in China at the time
• Majority of clinical data collection occurs in
China
– Data collection in China presents a variety of
challenges
Challenges of Data Collection in China
• Paper forms requested by study teams
– Required to retain the original data on paper forms by IRB or
departments
– Not comfortable with computer interface for direct data entry
• Limited internet access in rural areas
• Language barrier / low literacy in rural areas
– Potential for subjects to not be able to read and understand survey
– Not all interviewers are native speakers
– Variety of dialects in China – not everyone is fluent in Mandarin,
especially in rural areas with older population
• Data collection via tablets requested
– Superior battery life to laptops
– Generate additional interest in study participation
Overview
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Background
Optical mark recognition
OpenClinica on bootable USB drive
Embedding audio files into OpenClinica CRFs
OpenClinica on iPad mini
Optical Mark Recognition
• What is OMR?
– Recognizes check box and multiple choice bubbles
– Bubble forms / Scantrons
• Standardized tests, election ballots
– OMR software allows desktop computers to process data
• History of usage in clinical research
– Proposed for use with health care data in the 1970s
– Popular in 1990s and early 2000s for transcribing to
database
– Recent shift towards EDC and tablets for data entry
Optical Mark Recognition
• Current implementation
– Paper forms still used by many studies
– Transcribe to EDC or other study management
software
– Scanners are faster and cheaper
• OMR software
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Remark Office OMR
Allows users to design their own forms
Works with all common image types
Exports data in many formats – Excel, SPSS
Optical Mark Recognition
• For studies using paper data collection forms
– Requirements of some studies
– Paper forms can be used without internet access or
power
– Multiple surveys can be administered at a time with
self-reporting forms
• Increases efficiency and accuracy of data transfer
from paper forms to OpenClinica
• Cost-effective solution if reused for multiple
studies
Process Overview
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Design forms using Remark software
Create template for reading scanned images
Collect data and scan completed forms
Extract data using Remark image reader
Use Python script to convert data into
OpenClinica XML import format
• Import data into OpenClinica
1.
Capture data using paper data
collection forms
3.
Use OMR software to read
data from the scanned image
2.
4.
Scan completed
form as an image
Import data into
OpenClinica
Form Design
• Can use any word processor or desktop
publishing software
• Use bubbles for multiple choice questions
– Special font provided by Remark
• Can also set up areas for text recognition
– Remark does not have handwriting recognition
• Requires plenty of whitespace between
bubbles and text recognition areas
Form Design
Template Design
• Print and scan blank form for template base
– Insures layout will match scanned completed forms
• Open image in Remark template editor
• Highlight areas with bubbles and text entry
– Assign labels and values to bubbles
– Allows grouping of questions with same responses
(i.e. Likert scale)
• Create OpenClinica CRF first, and match the
region names to the OpenClinica item names
Template Design
Blue region: Text
Green region: OMR
Specify number of bubbles and
respective values in properties
Data Collection and Scanning
• Forms should be completed by filling in bubbles
– Check and ‘X’ marks can be too light or extend into
other bubbles
– Dark pen gives optimal results
• B&W setting works well if forms are filled out
correctly
– Grayscale can pickup lighter marks or text
• Minimum of 150 dpi recommended for OMR
Image Reading Process
• Displays form region during reading process
• Detects missing or extraneous marks
– Pauses reading for correction
• Detects written text in text regions
– Pauses reading so user can enter text
• Setting to identify and ignore large ‘X’ marks
– Allows users indicate incorrect marks
Conversion to XML Format
• Export data from Remark in tab-delimited text
file
• Add subjects to OpenClinica
– Allows script to query subject IDs
• Get study and form IDs from OpenClinica
• Python script reads data from text file and
converts into OpenClinica import format
Conversion to XML Format
Tab-delimited format
with header
XML Format
Importing Data
• XML file configured for OpenClinica’s Import
Data feature
• Performed by interviewer if tracking
interviewer is important
• Subjects must be created in advance with our
method
– Could use web services to automate the subject
creation process
OMR in Practice
• Used for 2012 summer project for UM medical
students
– Survey on knowledge of Hepatitis C and motivation
for clinical research participation
– OMR forms used at UM and at rural area near Beijing
• Subjects at UM completed forms on their own
– Multiple subjects taking survey at a time
– Clear instructions are essential
• Forms filled out by interviewers in China
– Accuracy was much higher than UM forms
Efficiency and Accuracy
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Used OMR process for JI-supported medical student
project
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64 forms entered with entry from paper form, 111 forms
entered with OMR process
7 minutes per form for data entry
2 minutes per form for entire OMR process
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Scanning, reading, and importing
Scanned 90 sheets at a time
Efficiency of OMR improves as more data is proccesed at a
time
OMR error rate of 2.2% compares favorably with data
entry error rates from published studies of 2-10%**
Overview
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Background
Optical mark recognition
OpenClinica on bootable USB drive
Embedding audio files into OpenClinica CRFs
OpenClinica on iPad mini
Bootable USB Drive
• Developed by Manhong Dai
• Bootable USB drives running OpenClinica on Linux OS
– Can run OpenClinica on laptops without internet access
– Cost-effective if interviewers already have their own
laptops
– No need to set up software on interviewer’s laptops
– Single configuration for multiple computers
– USB drive can be transferred between computers
• Interviewers could share a single USB drive if not conducting
surveys at the same time
Features
• Complete setup of Linux, Apache, Tomcat,
Postgres, and OpenClinica on 8GB USB drive
• Persistent
– Allows changes to be saved between sessions
– Entire setup can be backed up and/or copied to new
USB drives
• Automated backup of OpenClinica database
• Direct connection to server at U-M to provide IT
support
Operating System
• Unetbootin
– Software to create bootable USB drives for Linux
– Supports many distributions out of the box
• Can supply ISO file to use other distributions
• Lubuntu
– Lightweight version Linux distribution based on
Ubuntu
– Targeted at users who don’t use command line
– Very low hardware requirements
– Up-to-date drivers supporting most laptop hardware
Operating System
• Casper
– Creates “Live” USB
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Run preinstalled operating system from read-only media
Configured automatically by Unetbootin
– 4GB allocated to persistent storage space
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Need enough disk space for applications and OpenClinica
database
– Overlays the file system and copies all changes
– Image file can be saved as regular file on Windows or
Mac
Drivers and Software
• Some laptop hardware may require additional
drivers
• Older version of Postgres required by OpenClinica
– OpenClinica requires 8.4, default Lubuntu version is
9.2
• Default browser Chromium causes Javascript
errors in OpenClinica
– Firefox available for Linux
Backup and IT Support
• USB drives have a direct connection with U-M server
– Drives identified with a configuration file
• Files backed up automatically every 30 minutes with
shell script
– Requires internet access
– Script can also be run manually
– Only creates new backup if changes are detected
• Allows access to the Linux instance on the USB drive
– Access to OpenClinica on USB if needed
USB Drives in Practice
• Set up for 2013 summer project for UM medical
students
– Survey on motivations for participating in clinical
research
– Students will stay in China for 2 months
• Two study sites: PKU clinic and rural clinic
• No internet access at rural clinic
– Small budget for project; needs to cover flight and
living expenses
– Using student’s personal laptops
Wireless Local Network
Laptop booting from USB drive
operates as a local OpenClinica server
Laptop server connects to
router wirelessly or via Ethernet
Mobile devices connect to
the laptop server through a
wireless network
Overview
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Background
Optical mark recognition
OpenClinica on bootable USB drive
Embedding audio files into OpenClinica CRFs
OpenClinica on iPad mini
Embedding Audio Files
• Requested for surveys collecting data in rural
China
– Concerns over literacy of subjects and language
barrier
• Ensures consistent administration of survey
• HTML entered in “RIGHT_ITEM_TEXT” column of
OpenClinica CRF Excel spreadsheet
– HTML5 <audio> tag
– <embed> tag included for older browsers
Embedding Audio Files
<audio controls preload>
<source
src="/OpenClinica/audio/section1/1.1.mp3"
type="audio/mpeg">
<source
src="/OpenClinica/audio/section1/1.1.ogg"
type="audio/ogg">
<embed autostart="false”
src="/OpenClinica/audio/section1/1.1.wav">
</audio>
Audio controls in Firefox
HTML5 <audio> tag
• Standard for playing audio files
• Supported in all popular modern browsers
• Different browsers require different formats
– IE only supports MP3 files
• Audio player built into browsers
– User does not need to install plugins
Implementation
• IE only supports MP3 format, but Firefox does
not support MP3 in all versions
– Need both MP3 and Wav/Ogg formats
• Audio files stored in directory in top
OpenClinica directory
• Using <audio> tag avoids need for additional
browser plugins
Audio Files in Practice
• Embedded in CRFs for 2013 summer project for
UM medical students
– Rural site has older population with low education
and literacy levels
• Higher chance for older people to not speak Mandarin
fluently
• Difficulty of reading survey increased by medical terms
– Students are not native Chinese speakers
– Subjects that need to have questions read to them will
hear the same file
Overview
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•
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•
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Background
Optical mark recognition
OpenClinica on bootable USB drive
Embedding audio files into OpenClinica CRFs
OpenClinica on iPad mini
OpenClinica on iPad mini
• Study team request to support data collection on iPad mini
• Want to keep OpenClinica as standard software for data
collection
• Chrome instead of Safari
– Also need to update Javascript libraries for full functionality
• Limit number of questions per section in CRFs to reduce
scrolling
• Modifications to interface required
– Input elements and buttons are too small to select
– Constantly zooming in and out undesirable
– Images needed to be resized for some interface buttons
Modifying OpenClinica with CSS
• CRFs can be modified using inline styles
– Increasing size of text and input elements for CRF not enough
• CSS (Cascading Style Sheets) allow us to:
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increase spacing between elements
increase size of elements not in CRF
modify other forms (Add New Subject, Schedule Study Event)
hide input elements not used by studies
• Insert separate style sheet instead of editing current file
– Avoid changes to code; makes upgrading difficult
Modifying OpenClinica with CSS
• Include new style sheet
– Required to add one line to code for pages we
want to modify to link to our style sheet
– Use media query to only change appearance when
resolution is below a specific value
• Resolution of iPad mini is 1024x768
• <link rel="stylesheet" href="includes/ipad.css" type="text/css"
media="screen and (max-width: 1024px) ">
• Desktop version is unaffected unless they decrease
width of browser
Modifying OpenClinica with CSS
• Target elements with CSS selectors to avoid
making global changes
– CSS attribute selector to specify form names
form[action='AddNewSubject'] td,
form[action='CreateNewStudyEvent'] td {
padding: 3px;
}
– ID selector
#login form,
#login form input {
font-size: 16px;
}
Modifying OpenClinica with CSS
• Hide elements on Add New Subject form
form[action='AddNewSubject'] input[name='submitEnroll'],
form[action='AddNewSubject'] input[name='submitDone'] {
display: none;
}
• Resizing buttons
– Buttons use a fixed image that we can’t resize
– Remove image and recreate button using CSS
#login form .loginbutton {
background-image: none;
background-color: #789ec5;
padding: 0.2em 0.5em;
border-radius: 0.3em;
}
Login Form
Add Subject Form
Schedule Study Event Form
Case Report Form
OpenClinica on iPad mini
• Planning to use for study on Fatty Liver Disease in
Pinggu
– Most data collection will take place in very highvolume clinics
– Interviewers will have to move around and cannot
keep a laptop charged
• Tablets have superior battery life
– Study team is also expecting that using tablets for
data collection will generate extra interest
– Uncertain about reliability of internet access – may try
to use laptop as portable server
Combining Methods
• 2013 student project is using elements of all four methods
– Data will be collected at both U-M and China
– OMR forms are being used by interviewers at U-M clinics
• Waiting times are short; patients can finish form in examination room
– USB drives will be used by interviewers in China
• Internet access unreliable
• Small budget didn’t leave room for new hardware
– Audio files embedded in CRFs on USB drives
• Interviewers are not native speakers
– CSS modifications applied to OpenClinica on USB drives
• Default OpenClinica font size is much too small for Chinese
Future Improvements
• OMR process
– Create subjects with web services
– Hoping to implement this for U-M subjects of current 2013 summer
project
• USB drives
– Initial testing with USB 2.0 drives, later testing showed significantly
increased performance with USB 3.0 drives
– Test portable laptop server and wireless network
• May use setup for Fatty Liver Disease project
• OpenClinica on iPad mini
– Working on converting 30 page survey into OpenClinca CRF
• Anticipating additional modifications for later parts of the form
– Searching for better solution than resizing button images
Contact Information
Andy Lin
Bioinformatics Programmer, Molecular and Behavioral
Neuroscience Institute, University of Michigan
andylin@umich.edu
Acknowledgements
Molecular and Behavioral Neuroscience Institute
Microarray Lab
Manhong Dai, Fan Meng
UMHS-PUHSC Joint Institute
University of Michigan
Peking University
BRBI Core
Kai Zheng, Danny Wu, Ching-Ping Lin
Hepatitis C Project
Anna Lok, Sherry Fu, Elizabeth Wu
Fatty Liver Disease Project
Liz Speliotes
BRBI Core
Yanfang Wang, Yao Chen, Yuliang Huo
Hepatitis C Project
Lai Wei, Huiying Rao
Fatty Liver Diease Project
Linong Ji
Funded by the UMHS-PUHSC Joint Institute
http://www.puuma.org