2. Introduction
As post-marketing studies are more prevalent today, the based architecture. The use of web-enabled technologies
FDA and pharmaceutical companies have taken greater support more complex and flexible trial designs2.
interest in direct patient information1. For many years
this information was accumulated via traditional ePRO Overview
collection methods, including paper forms and ePRO is simply the collection of data directly from
Interactive Voice Response Systems (IVRS). With the patients into a database. The concept is not new - with
introduction of the Internet and a plethora of mobile innovators like Health Hero Network and a variety of
devices now in use, more advanced methods of handheld diary systems active in the market for the past
gathering data speed up data collection, improve data 20 years - but the adoption of ePRO technologies is still
quality, and rapidly merge with readily available emerging and undergoing scrutiny. At a recent ePRO
Electronic Data Capture (EDC) systems. These Electronic conference, an open discussion on ePRO methods was
Patient Reported Outcome (ePRO) systems are deployed characterized as a “volleyball match” 3. The development
across a wide range of platforms and solutions. Although and deployment of ePRO is still relatively new and is
modular and disparate systems are the norm, a single slowly replacing paper diaries, mailed forms, and IVRS.
ePRO/EDC system offers a superior solution by allowing ePRO adoption comes at a time when smart phones,
all study data to be readily available without incurring tablets, and the Internet are readily available to the
integration costs. This integrated implementation gives majority of the population. Internet availability in North
sponsors the ability to employ unified analysis strategies America currently stands at more than 75 percent
in a timely manner with a significant reduction in cost. penetration4 and cellular phone penetration now stands
at more than 80 percent for the same area5. With this
EDC Overview new technology study, sponsors are pushing the market
EDC systems have been in use for more than 20 years in towards an inevitable domination of ePRO6 to save time,
a variety of data capture modalities. By having an money and improve data quality.
investigator enter data directly into a clinical database,
the normal steps of send and receive created by paper
are eliminated. It was predicted that the use of EDC 7
technologies would yield cleaner data and the source
data would be more readily apparent. EDC systems
began with terminal-based clients, progressing to thick-
client applications and eventually to web-based
applications. In past years, back-end databases ranged
from Oracle and Microsoft’s SQL server to a variety of
homegrown flat files including the flat file structures of
SAS datasets. A variety of system types and architectures
still exist although as per last year’s review of EDC
companies at the Drug Information Association (DIA)
annual meeting, most companies had migrated to a web-
Increasing Technology Usage Awareness in EDC and ePRO
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3. Integration of Modular and Disparate Systems
Anyone searching the Internet or available journals will with two separate vendors. A series of edits or range
find dozens of articles advocating the integration of EDC checks that could apply to both systems must be
and ePRO data, providing sponsors exciting ways of programmed separately with no common sharing
implementing these integrations through new tools and mechanism. When the technologies are complete, there
a series of seemingly never-ending database still may be integration challenges. Studies where patient
manipulations. Although this paper will not examine any visits trigger EDC data entry become more challenging as
specific integration it can be safely stated that data must be transferred between the two systems in a
integration of technology and clinical system is not a timely manner.
simple matter. Approaches to integrate have generated
The process of data integration can also add considerable
dozens of whitepapers. From a validation perspective,
complexity to any study. Usually, the data from multiple
integration involves a significant amount of testing,
systems is combined inside a separate single-data
verification, and paperwork.
warehouse repository with no clean cross reference to
The general approach of integrating modular or the source records or the source system. Again, unless
systems can be less complex if planning begins early. The careful planning and execution is done, there would be
necessity of a common data naming convention or at massive risks. A difficult and illusive risk to manage is
least well defined structure creates a series of import time. For example, when were both exports to the data
maps. These can be utilized to combine the two systems warehouse made? What are the common data
into a single clinical database and made readily available elements? Which data wins in the event of duplication?
for statisticians. Some large pharmaceutical companies Is only clean data exported? What is the proper way to
have created massive data definition libraries to address handle data that is out of range? How is free-text data
integration issues, although many other companies use handled9? Other such questions need to be asked and
standardized conventions (i.e. CDISC, CDASH8). answered in any type of data integration.
Even with the completion of necessary data mapping, With a solid plan for integration, the necessity of proving
need for proper design, development, testing, and that each integration activity has produced the same
validation still exists and can become costly unless result can be daunting, considering that regulations may
communication and planning are well documented and be in effect10. A proper validation should consist of
finely executed. Without the necessary proof that data multiple iterations to ensure the import is consistent.
mapped to a particular system is being passed correctly it Another option may be to review documentation from a
is possible that errors may get introduced into the clinical vendor that has validated its tools to minimize risk. Even
database, possibly creating significant risk to the if such documentation exists, it may still be necessary to
sponsor. test the study data during the validation and UAT portion
of study startup.
Using multiple data-collection systems instantly has a
direct impact on sponsors and study members as both The end result of integration, though potentially
systems require setup. Even with modern setup tools the accurate, means additional cost as the systems or
need for setup time, constant communication, and modules are compared to the data warehouse.
strong project management can have a financial impact.
From a technology standpoint, the sponsor is basically
paying to set up two complete data-collection systems
and under many circumstances, the sponsor is working
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4. The Single-System Approach
With the need for additional post-market studies and the The need for multiple vendors and additional consultants
necessity for data to rapidly prove endpoints and publish, to design the integration methodology is also reduced.
new systems are being released which eliminate the The Acceliant eClinical Suite manages ePRO and EDC by
initial need for data integration. These systems represent defining an extra layer in eCRF setup. If a CRF is defined
multiple technologies that exist in a single as EDC, it uses a standard EDC display methodology and
implementation and share common definitions, such as is accessed via the EDC portal by sites, data managers,
data access and data export. monitors, and other necessary users as defined by the
An example of a true single system is the Acceliant technology. If, however, the CRF is defined as ePRO, the
eClinical Suite11 where multiple solutions are housed in a page is also accessible via an ePRO portal interface with a
single data warehouse and managed by a single more aesthetic look and feel as defined by the sponsor.
interface. Utilizing the Unified Trial Builder (UTB), an Thus, forms that are patient facing are presented to
experienced data manager can design EDC, CRF, and patients with a very simplified interface, whereas the
ePRO data collection instruments that can be deployed same forms are available for other users as standard EDC
quickly and efficiently. ePRO and EDC pages, being part forms. As they share the same database, updates to data
of the same data-definition table, eliminate the need for are in real time for both EDC and ePRO without an export
integration. Consequently, costs are reduced in the areas or import of collected data.
of validation in the management of multiple systems.
Web Services
Site Users Site Admin Patients
ePRO
Web HTTP / HTTPS
System Admin
Web Services
Presentation Layer
Web HTTP / HTTPS
UI Process
UI Component
Component
Study Data
Business Logic Layer PHI
User Data
Service Agent
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5. The ePRO portal allows patients to review predefined in both EDC and ePRO, allowing range checks to be
information about the study, documents etc. that the applied to the variable in ePRO with a simple user action.
sponsor has defined for the system and also to access The data collected from patients can function as a trigger
pages as defined in the UTB for ePRO access. Because for more types of follow-up edits in the EDC portal. Data
patients access the ePRO portal, it can be used to collected from a patient may initiate an event, create a
enhance the branding experience and can contain and query for the site to research, or begin a complex process
disseminate information that is necessary for patients. that creates reports or sends email notifications to the
Upon activating the option, a physician and a patient can appropriate data manager or safety associate.
communicate via the patient portal and the EDC portal
Utilizing a single system like the Acceliant Clinical Trial
through a convenient messaging system. Because certain
Suite can also reduce validation costs. Instead of creating
fields can be marked for privacy by the designer,
validation plans and running acceptance tests for
confidentiality is guaranteed as this data can be
multiple systems, a single plan and acceptance test
completely segregated in the database system or marked
covers both EDC data and ePRO data and eliminates the
as not exportable or even not viewable by certain users.
need for integration validation.
ePRO pages have more flexible controls such as sliders,
pictographs, push buttons, and more to make the patient Conclusion
experience, for the same fields, as simple as possible. The necessary endpoint for any clinical trial, registry, or
other type of study is data availability. With cost and
The EDC portal allows a clinical user or a site to enter
time being critical factors in the implementation and
data, query standard data, or answer queries as defined
execution of any type of data collection effort, the ability
in the study protocol. The sponsor or data manager also
to combine systems in a single technology is a distinct
has the ability to review more types of data, enter notes,
advantage. During the next several years, the push for
review audit records, code data or review auto-coded
more simple systems will be necessary to ensure quality
data, upload or review documents, and generate and
and cost-effective data. Although modular and disparate
review reports on data and the state of the system or
systems are currently the norm, a single ePRO/EDC
export data. The powerful data-export system can create
system offers a superior solution by allowing all study
multiple types of data exports ranging from Excel to SAS
data to be readily available without incurring the costs of
datasets along with complete data definitions. The data
integration. This single implementation can give sponsors
export is generated in real time and throttles against the
the ability to create analysis in a timely manner and at a
database so there are no lapses in accessibility for any
lesser cost. Utilizing a single solution, sponsors can also
user, ePRO or EDC, to the system. The EDC portal also
reduce user frustration in their electronic study
has a built-in messaging system, scheduling system, and
implementations and achieve multiple successes within a
other features that can assist site, sponsor, and data
study implementation.
manager in proper management of their study.
To ensure data cleanliness all EDC and ePRO systems
utilize range checks and different types of edits. Edits in
ePRO are not as common, considering the data source is
the actual patient. However, range checks in these
systems are prevalent to reduce patient
misunderstanding or data-entry errors. The Acceliant
eClinical Suite utilizes the same capabilities for variables
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6. Reference and Research
1. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/ucm070766.htm
2. http://www.clinicaldiscovery.com/readArticle.aspx?articleId=60
3. http://www.lifescienceleader.com/blogs/contributing-editors-2/item/3950-insights-and-a-peek-into-the-future-for-pro--epro
4. http://www.internetworldstats.com/stats14.htm
5. http://www.mobilemarketer.com/cms/news/research/1576.html
6. http://www.crfhealth.com/sites/default/files/epro-articles/ePROvsPaper_CRFHealth_AppliedClinicalTrials_June%202010.pdf
7. http://www.crosnt.com/events/the-importance-of-epro-edc-integration-for-the-clinical-trial-environment-en.html
8. http://www.cdisc.org/
9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041580/
10. http://www.fda.gov/RegulatoryInformation/Guidances/ucm125067.htm#iiic
11. http://www.acceliant.com/
General research supporting this white paper:
1. http://www.slideshare.net/challPHT/why-paper-diaries-should-be-banned-in-clinical-trials
2. http://appliedclinicaltrialsonline.findpharma.com
3. http://www.ngpharma.com/article/The-ePRO-evolution
Biography
Andrew Allen Smith:
Andrew Smith has been designing IT solutions for more than 25 years. With a diverse career spanning multiple
industries, Andrew applies energy, experience, and education to create effective technology implementations. For the
past 13 years Andrew has been reviewing, designing, and maintaining clinical technologies. A frequent speaker at Drug
Information Association (DIA) meetings and other industry venues, Andrew is constantly looking at new technology and
new approaches in technology to address the changing needs of clinical research. Andrew was on the advisory council
for the DIA for four years and continues to stay in touch with technology through special interest activity communities
and other groups.
Ven Thangaraj:
With nearly 20 years of experience in the biomedical field, Ven Thangaraj, CTO, has been responsible for Acceliant since
the platform’s inception. He partners with numerous clients in evaluations, deployment, and operations of clinical trials
using Acceliant. He also consults for top management and data management clients at pharmaceutical, device
manufacturers, CROs, and biotech companies on clinical trials from lab phase to all further stages of the lifecycle. Ven
earned a B.S. degree in biomedical engineering from the University of Illinois in Champaign-Urbana, Illinois and a second
B.S. degree in mechanical engineering from Rensselaer Polytechnic Institute in Troy, New York. Throughout his career,
Ven has authored numerous scientific articles and abstracts. He is a 2012 recipient of the Frost & Sullivan Award for
technological innovation in the healthcare industry.
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