Adapting OpenClinica for International Collaborations Andy Lin University of Michigan June 21, 2013 OpenClinica Global Conference 2013.

Adapting OpenClinica for International Collaborations

Andy LinUniversity of Michigan

June 21, 2013OpenClinica Global Conference 2013

Overview

• 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


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– 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

• 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

2. Scan completed form as an image

3. Use OMR software to read data from the scanned image

4. 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 DesignBlue region: TextGreen 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• Used OMR process for JI-supported medical student

project– 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

• 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


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• Run preinstalled operating system from read-only media• Configured automatically by Unetbootin

– 4GB allocated to persistent storage space• 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 NetworkLaptop 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


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


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:

– 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 high-

volume 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 LinBioinformatics Programmer, Molecular and Behavioral

Neuroscience Institute, University of Michigan

[email protected]

Acknowledgements

University of Michigan

BRBI CoreKai Zheng, Danny Wu, Ching-Ping LinHepatitis C ProjectAnna Lok, Sherry Fu, Elizabeth WuFatty Liver Disease ProjectLiz Speliotes

Peking University

BRBI CoreYanfang Wang, Yao Chen, Yuliang HuoHepatitis C ProjectLai Wei, Huiying RaoFatty Liver Diease ProjectLinong Ji

Funded by the UMHS-PUHSC Joint Institutehttp://www.puuma.org

Molecular and Behavioral Neuroscience InstituteMicroarray LabManhong Dai, Fan Meng

UMHS-PUHSC Joint Institute

Adapting OpenClinica for International Collaborations Andy Lin University of Michigan June 21, 2013 OpenClinica Global Conference 2013.

Documents

openclinica slide

data entry slide

data management slide

forms extract data

omr slide

china data collection

capture data

original data