www.oracle.com www.touchbriefings.com BRIEFINGS Clinical Trial Management: Enabling Operational Efficiency Contents: New Challenges Call for Innovative Approaches Rachel Yang, Oracle HealthSciences Technology as the Enabler of High Performance—The Place of Clinical Trial Management Systems Henry Levy, Accenture Implementation of a Clinical Trial Management System Jennifer Hunt, Genzyme Clinical Trials Management of the Future Jeannie Inge and Jason Packwood, PRA International Clinical Trial Management Systems in the Wild Kevin Jarrell, Duke Clinical Research Institute eClinical Visions HEALTH SCIENCES
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Director, Product Strategy, Oracle Health Sciences Global Business Unit
The way the biopharmaceutical industry conducts clinical trials is
undergoing a remarkable transformation. Coupled with this much-
needed evolution are new challenges specific to the increasing role that
information technology will play to enable the new clinical
development landscape.
Of the many challenges facing the biopharmaceutical industry today, the
critical need for greater operational efficiency in clinical drug
development is paramount. With flat and even declining productivity,
rising research and development (R&D) costs, more complex pre-
approval trials and large post-approval studies driven by the shift toward
biological agents, and increasing regulatory demands, it is essential that
clinical trials are managed more effectively and efficiently. While
progress has been made in addressing these challenges, companies are
increasingly turning to clinical trial management systems (CTMS) to
improve trial efficiencies, cut trial costs, and enhance the productivity
of trial participants.
The Globalization of Clinical Trials
The global clinical trial, while not new to either sponsors or clinical
research organizations (CROs), is becoming more prevalent. Clinical trials
are increasing in size and complexity and more global trials are being
conducted with sites across diverse geographical regions. The predicted
trend is that there will be a significant shift from North America/Western
Europe to the Asia-Pacific region (APAC). Between 2008 and 2010 the
percentage of trials conducted in North America/Western Europe is
expected to fall from 55 to 38% (see Figure 1).1 Clinical trials conducted
in APAC countries offer potential cost savings as well as large patient
populations, particularly of treatment-naïve patients. This shift will also
have certain implications. Sponsors and CROs will need to support all
operational aspects of global trials: languages, logistics, access control,
regional requirements, and region-specific business processes.
Furthermore, it will be necessary to understand and meet local regulatory
requirements. To manage global trials more efficiently, many companies
turn to commercial CTMS. These CTMS are typically implemented as
enterprise applications.
A fundamental value proposition of an enterprise CTMS is the provision
of a centralized trial repository, which enables standard trial management
processes across the enterprise and provides end-users, who increasingly
are more geographically diverse, with realtime data visibility into study
progress. However, this does not necessarily mean that everybody who is
involved in a study should have access to all information about it.
Organizations should balance the need to empower their employees
with access to available information against keeping tight control over
data access, allowing only those with proper authorization into the
appropriate files. Fortunately, technology solutions exist that provide
the access control necessary for the clinical trial industry, as well as tools
that significantly reduce the administrative overhead.
The globalization of clinical trials needs to be truly worldwide rather than
just a process of more trials conducted in different locations. This will
require global unified systems with built-in functionality that supports
specific regional needs. The current mindset, however, is still more or less
focused toward the traditional North America/Western Europe
requirements and supporting prevailing business needs. For a truly global
system, this view needs to change to ensure individuals and departments
have an understanding of where they fit into the business process. Regional
units need to understand how their work affects others in the process so
that effective collaboration can take place. It is also important to assess the
impact or implication that local infrastructure and culture might have on
conducting clinical trials in developing countries. Understanding the local
environment and requirements often drives innovation that brings about
substantial impact. Innovative solutions that are very site-focused, very
pragmatic, and very specific to the local infrastructure may overcome
barriers. For example, patient follow-up is a significant issue in China. A
large Chinese CRO has proposed utilizing mobile technology, in the form
of cell phones, as a component of its site management system. The
proposed system would allow stakeholders to send the alerts or messages
via SMS, or push reminders to patients regarding visits. This form of
collaborative tool, along with better data visibility, will help clinical research
associates (CRAs) better manage their sites and increase study compliance.
Increased Outsourcing of Clinical Trials
It is estimated that 20% of the biopharmaceutical industry’s R&D
spend is on outsourcing. Coupled with the increasing globalization of
Rachel Yang, MD, PhD, is Director of Product Strategy atOracle Health Sciences Global Business Unit. She joinedSiebel Systems in June 2000 as a Product Manager to leadthe development of a new clinical trial management system(CTMS). Working closely with life sciences customers andpartners around the world, she was instrumental indeveloping and delivering the industry’s first integrated,robust CTMS, Siebel Clinical. Under Dr Yang’s leadership,Siebel Clinical has quickly become the market leader and a
de facto CTMS standard for some of the biggest life sciences companies, including Pfizer,GlaxoSmithKline, Johnson & Johnson, Roche, Schering Plough, PRA International, andPharmaceutical Product Development (PPD). Since Oracle acquired Siebel Systems in 2005, Dr Yang has been working in Oracle’s Life Sciences organization with a focus on providingstrategic directions on Oracle’s clinical trial management solution for the life sciencesindustry. Prior to joining Siebel Systems, she worked at PPD in various capacities. She is listedas an inventor of one US patent. Dr Yang received her MD from Shanghai Medical University,now part of the Fudan University in Shanghai, China. She was awarded a full scholarshipfrom the University of Virginia at Charlottesville to study yeast genetics and molecular cellbiology, where she earned a PhD from the Department of Microbiology.
Having engaged a consultant to come in and help with the process of
selecting a system, the next step was to define Genzyme’s requirements
and needs from a CTMS. It was also important to examine the most
crucial standard operating procedures (SOPs), breaking them down into
process maps to see where a CTMS could be utilized to automate
the process. Only once this had been done was it worth looking at the
different CTMS options available and matching them up with
Genzyme’s needs. All of the top choices came in and presented.
Although the different systems had superficially very similar
functionality, significant differences existed. The Siebel CTMS from
Oracle has a sales history and therefore has a built-in concept of what
it takes to make a study site: the doctor, who is the ‘contact’; a
hospital as an ‘account’; and then the study protocol on top. The
Siebel system also had an inherent flexibility to permit customization
to conform to Genzyme’s particular processes. In addition, it had the
best feedback and very good references of the choices presented.
Overall, selection of a system was a long and challenging process. It
involved comparing Genzyme’s requirements against each of the system’s
capabilities. However, while requirements and capabilities may align on
paper, until a system is deployed and utilized both the strength of the
requirements and the depth of the capabilities cannot be fully tested.
Deployment Timescale
The initial deployment occurred in February 2007, and by the end of 2008
Genzyme will have completed the second phase of development, which
includes many updates and enhancements. This process has differed from
Implementation of a Clinical Management Technology System
Jennifer Hunt is Senior Director of Clinical Research atGenzyme Corp. Since joining Genzyme’s Clinical ResearchDepartment in 2001, she has worked on programs forultra-orphan lysosomal storage disorders, before movingin early 2008 to the newly formed Global ClinicalOperations Group. For most of her tenure, she was theglobal Biomedical and Regulatory Affairs team leader forMyozyme®, which was approved in 2006 to treat Pompedisease. She is currently the business lead for Genzyme’s
Clinical Trial Management System and a member of the Global Clinical Research Council.Prior to joining Genzyme, Ms Hunt was Manager of Clinical Research at Diacrin, abiotechnology company focusing on xeno- and cell transplantation. She began her careeras a Clinical Research Associate at Quintiles. Jennifer has a BSc in biology with aconcentration in biotechnology from the State University of New York College ofEnvironmental Science and Forestry at Syracuse, and an MSc in management from Lesley University.
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that of other companies as Genzyme’s CTMS went live with the knowledge
that, while the initial design was not perfect, sufficient useful functionality
would drive end-user utilization, which in turn would create the helpful
feedback for additional releases. This has proved to be the case, with an
increasing number of users adopting the system (see Figure 1).
One of the trade-offs is that the more customized a system is to meet
specific needs, the more of a challenge it can be to upgrade to the
next standard. While Siebel CTMS is highly configurable with the
Siebel Tools and provides full upgrade paths for configurations,
excessive customization is highly discouraged as it can make upgrades
challenging. Judicious use of the Siebel Tools to configure the
application is the key, and in fact Genzyme has been able to keep
configuration to less than 15%.
Organizational Linkages
Bringing in a CTMS creates waves. It is not an enclosed system: there
are many opportunities for integration with other systems and
opportunities to share data. Sometimes that will include taking a step
back and determining the authoritative source: identifying the sole
place within Genzyme where a data element is first entered, regardless
of system, and then sharing it. Doing this makes it possible to avoid
redundancy and duplicative entry, which can lead to errors.
Similarly, along with unifying the data system, by creating the Global
Clinical Operations group the hope is that the task of running this
system can be centralized. This will allow others in Clinical Research
more time to focus on conducting clinical trials. Global Clinical
Operations can assume responsibility for not only executing CTMS but
also looking to create synergies elsewhere as the company as a whole
moves toward an even more global outlook: expanding into China and
India, for example. It is important to be able to create consistency,
even while running studies in several geographies across different
therapeutic areas in each of the business units. This group will help
move resources quickly and provide senior management with a
common understanding and insight into the progress of the clinical
development programs. It is also intended to be a resource for all new
studies. If someone is initiating a new program, he or she can contact
Global Clinical Operations and get help in laying the foundation,
including finding the resources, entering the protocols into the CTMS,
retrieving the information, and any other technology needs.
Within Global Clinical Operations is the Clinical Process and Technology
group, which manages the CTMS, including evaluating the use of
electronic trial master files, dealing with reporting issues, planning for
studies, and helping people use the technology to make their jobs
easier. There are also groups that focus on resourcing, contracts and
vendors, study feasibility and subject recruitment, pharmacy-related
issues, and, lastly, handling SOPs, best practices, and training.
Learning the New System
Having now implemented CTMS at Genzyme, there is an opportunity to
reflect on the other in-house systems in order to identify clinical
processes that do not currently have an effective tool and see whether
the CTMS can help solve them. It has also been very helpful for Genzyme
to become active with the extended Oracle user community. The system
is very flexible and different companies are using it in a variety of ways.
Communicating with other organizational users of Siebel CTMS is a
valuable strategy: it has allowed us to share our company’s experiences
and best practices with other firms, and vice versa. For example, one of
these organizations is a pharmaceutical company that is much larger
than Genzyme, and there have been periods of collaboration over the
past two years that involve sharing non-confidential ideas about training
and system enhancements, often resulting in suggestions for
improvements that are then passed on to Oracle.
Overall, adoption at Genzyme has been very good. People have been very
pleased with the functionality. The CRAs, for example, have to create a
report after a site visit; previously this was written using a Microsoft Word
template, but with the CTMS all of the templates and all of the questions
are now in the system, making the process of reporting simpler and
quicker. One of the main intentions of the system is to try to stop people
from creating their own spreadsheets to track details about any given
study. A survey was conducted at Genzyme’s European headquarters in
Figure 1: New Clinical Trial Management System Users Created
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2006 2007 2008Dec Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct
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Amsterdam that calculated how many spreadsheets people used before
the implementation of CTMS compared with afterwards. Between April
and December 2007, there was a 20–40% decrease in the number of
spreadsheets used, but not total elimination. However, instead of
banishing the spreadsheets, following the implementation of phase one
the users in Clinical Research were asked what they were still tracking in
spreadsheets, and as a consequence several pieces of functionality are
being added in phase two.
Issues and Teething Problems
The process of deployment and assessment has not only uncovered
additional functionality to be added, but has also highlighted
unnecessary functionality that can be removed. This includes some
requirements determined prior to system selection. One example is the
ability to work and write reports within CTMS while users are offline.
This was considered useful for the CRAs who regularly travel across
the country and could not always connect to the Internet to access the
system. This capability enabled CRAs to have full access to CTMS
functionality without being connected to the Internet. The idea was
that CRAs would synchronize at least daily to upload all of their offline
reports into the system and download any changes from the system.
While the remote capability did help CRAs be more productive while
on the road, it also brought some unanticipated challenges. For
instance, if a contractor suddenly leaves the company with information
stored in his or her computer, this weakens the system and raises a
potential issue of confidentiality. If synchronization is not completed
frequently, data integrity and speed can be affected. After weighing
the pros and cons of enabling remote capability, Genzyme has now
made a decision to disable the remote capability. Currently, Genzyme
issues wireless cards to certain staff who travel frequently so they can
log on through a mobile telephone system, connecting through a
private virtual network. In this way users are always securely
connected to the live system and no data are stored on laptops.
The ability to produce reports from the data contained within the
system has also taken time to develop. It would have been a very time-
consuming process to analyze and derive a top 10 list of reports in the
development phase. Therefore, an alternative is to allow ad hoc
reporting, which will be released shortly. This will be monitored and
the data collected so that it is possible to determine which reports
work and which ones do not, and which ones are very popular and
which ones less so. From the ad hoc reporting tool, a list of 20 or more
reports can be compiled and made available to all users in the system,
removing the need to use ad hoc reporting and creating uniformity
and speed.
We have seen benefits and cost savings since we started to use CTMS;
however, quantifying the cost savings remains a challenge. Costs can
be decreased in several ways: a task that used to take four hours to
complete may take only two hours with CTMS; therefore, people can
do more tasks. Alternatively, the actual external dollars now spent can
be compared with former spend: for example, a CRA’s trip report
would have previously been sent—signed with a wet signature—by
Federal Express; with CTMS, the approval process is completed
electronically. The actual costs have not yet been calculated, although
an administrative survey was carried out prior to the initial roll-out.
This survey addressed the time taken for common tasks; a
re-administration of the survey will be able to assess any change.
The Authoritative Source
A major revelation connected with CTMS is how much this system
affects those outside of Clinical Research and the need to engage
these groups. For example, metrics that help benchmark the efficiency
of Genzyme’s clinical trials rely heavily on data contained within
CTMS. Thus, there needs to be a reporting tool to allow data retrieval,
but it is also vital to ensure that the data are accurate and that there
is a high level of compliance.
In addition, terminology needs to be standardized so that protocols
can be tracked. A protocol may be active, planned, proposed, or
closed; a shortlist of standard nomenclature was vetted by Clinical
Research, but it became clear that other Genzyme departments may
interpret these terms differently. Therefore, there needs to be
consistent, technology-independent nomenclature overseen by one
Genzyme-wide group. A word proposed for a new protocol status can
be posted centrally and assessed by all users. For example, the word
‘active’ when applied to a trial seemed ambiguous, and was changed
to a status of ‘enrollment open.’ Once a decision such as this is made,
the system is then manually cleaned up and made consistent.
Applying the highest standards possible to the CTMS has
encouraged other groups to ask whether they can pull data from
the system because it has become the authoritative source—the
first place that any piece of data will be entered. People from the
business units use it to generate high-level reports about all of
Genzyme’s programs. Furthermore, given the US Food and Drug
Administration’s requirements for posting of clinical trials and results,
this type of information can also be drawn from the CTMS by
Regulatory Affairs Compliance groups. Such groups will have
additional data requirements that can in turn be added to the system
where appropriate.
By making CTMS the authoritative source, people will not have to
reinvent the wheel each time to deal with a specific problem. The
CTMS can drive best practices and help establish a common agenda
for a set of reports, allowing clinical professionals to focus on running
studies and, ultimately, getting products approved. The process of
determining which system to install and how to use and maintain the
system is a significant undertaking. Ultimately, successful adoption
should improve and streamline all functions within Genzyme and help
unite the different departments. A big part of the learning process
with CTMS is that simply installing a system is not sufficient to allow
declaration of success. There is much more work to be done to ensure
that a CTMS is useful, and to achieve and maintain these goals. ■
1. Touch Briefings; 2. Vice President for Information Technology, PRA International; 3. Vice President for Business Solutions, PRA International
As clinical trials grow larger and more complex, there is increasing
pressure on a company’s ability to conduct them efficiently. This has
led to the need for clinical development firms to implement new
technologies such as clinical trial management systems (CTMS) to
improve workflow efficiency. Furthermore, firms can maximize the
potential of systems such as these by using them in innovative ways to
cut the time and costs required to take a drug through development.
Clinical research organization (CRO) PRA International has
implemented some 20 enterprise systems in the last eight years. This
article will discuss PRA’s experience with these systems, primarily
CTMS, and how they have increased efficiency and reduced costs. It
also describes how PRA has leveraged its current technology to meet
new needs and how this bodes for the firm’s future. The article will
also look at ways to use CTMS to cope with changing trends and keep
pace with future developments in the field.
The Changing Face of Clinical Trials
Over the last 10 years, PRA has seen its client base grow dramatically.
It has gone from a company managing trials confined to one country,
for example in the US, Canada, or Germany only, to one that runs
huge projects spanning the globe, in some cases with sites in more
than 30 countries. As PRA has grown, the firm has had to adapt its
technology to deal with a changing customer base and more complex
clinical trials. When conducting multicenter trials based in 30 countries
or more, the communication overheads can be staggering. Creating
enterprise tools and developing solutions that can help to reduce that
overhead and help teams communicate more effectively is one of the
major challenges that clinical development firms face today.
As well as facilitating communication, a CTMS can also be used to
automate processes and cut administrative tasks to a minimum. The
technology addresses organizational issues, allowing a firm to manage
its resources with consistent control over all departments within
the company. An effective CTMS can reduce communication
overheads, support protocol feasibility, facilitate the management
of investigative sites, cut down on administration, and save money
in the process—something of extreme importance in the current
economic climate.
Clinical Trial Management Systems—A Brief History
In the early days of CTMS, the pharmaceutical industry was quite
conservative in its use of the technology owing to concerns over the
security of data and the safety of intellectual property. A CTMS was
also very costly to implement, with companies having to invest in large
amounts of hardware and training, not to mention the license cost.
However, times are changing. Developments in Oracle’s systems have
enabled CTMS to be offered at a lower cost than before, allowing more
companies access to the technology. Now, many companies are reliant
on CTMS technology to manage numerous trials. With this reliance has
come the demand for information and ease of access to this information
so that individuals can make rapid business decisions. This demand is
what has necessitated pushing CTMS tools to a new level of
performance, use, and scalability. In addition, the notion of transparency
between the client and CRO is paramount.
PRA’s experience using CTMS has been positive, and the key to that
success has been thinking ahead: the firm had been anticipating the
market and preparing its systems so that it could ‘slot’ a CTMS into the
established business model. The company envisioned a 10-year plan
(beginning in 1998) to create a standardized, robust, and scalable
information technology (IT) infrastructure that is able to adapt as the
business grows, taking on more and more complex trials. It has also
proved important to develop a standardized network infrastructure, where
all employees across the world have the same hardware and software, to
avoid complications with maintenance as the company expands.
At the fundamental level of the technology plan are the enterprise systems
themselves, which comprise various applications (see page 10). All the data
Clinical Trials Management of the Future
Jeannie Inge is Vice President for Information Technology (IT)at PRA International, and is responsible for the globalmanagement of PRA’s technology and telecommunicationsinfrastructure, application suites, and customer support. Withmore than 20 years of experience in business management,she has worked in marketing, business administration andaccounting, training, and compliance. For the past 14 yearsshe has focused on the development of corporate IT solutions.She began her career at PRA as a Project Manager and led
the implementation of Lawson Financials, clinical trial management systems (CTMS) (SiebeleClinical), and the Oracle adverse event reporting system (AERS), among other projects. Sheholds an MSc in information technology from the University of Virginia and is a certified Project Management Professional.
Jason Packwood is Vice President for Business Solutions atPRA International, spearheading various cross-functionalsystem and process improvement initiatives for the company.He has been working in the biopharmaceutical industry for 15years and has experience in clinical operations, informationtechnology, application development, data management, andthe implementation of quality management systems.Throughout his career, he has led the development,implementation, and validation efforts for various enterprise
systems, including Clintrial, eData Management, Oracle Clinical, statistical analysis software,and homegrown clinical trial management systems (CTMS). He also led PRA’s evaluation ofelectronic data capture (EDC) providers and the procurement process for identifying an in-houseEDC solution: ClinPhone EDC. Today, he is the system owner for PRA’s CTMS (Siebel eClinical).
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from here are stored in a data warehouse that can assemble the required
information as necessary, allowing it to be viewed via the delivery portal.
The nuts and bolts of this infrastructure include a standardized IT solution
on Dell Hardware, Microsoft platforms, and, largely, Oracle databases. The
infrastructure is based on Cisco Networks, with AT&T being the global
provider. As noted previously, the company boasts the success of 20
individual enterprise systems since 2000, all of which met project deadlines
and budgets. Among these notable industry leaders include:
The Duke Clinical Research Institute (DCRI) is the largest clinical academic
research organization (ARO) in the world. It combines clinical expertise
and academic excellence with the full-service operational capabilities of a
major contract research organization (CRO). The DCRI operates with an
approximate 50/50 balance between government-sponsored clinical trials
and industry-sponsored clinical trials, in addition to our academic work,
which makes us a niche player in the clinical trial arena.
One of the benefits of the CRO-type offering from an institution such as
the DCRI is that we have an academic aspect to our work. We have a real
desire to understand the research, understand what the data are saying,
and work out how that affects the patient. This attitude can be plainly
seen in different meetings, in the hallways, and within the DCRI in
general: there is a huge focus on patient care, which is the end goal of
every clinical trial.
My role is a Line of Business Owner: essentially, I represent the business
and the business needs. I am the day-to-day decision-maker on what we
do with our clinical trial management system (CTMS) from Siebel (now
part of Oracle). I co-ordinate with the Director of Clinical Operations.
Together with the Information Technology (IT) Product Manager, I am
responsible for growing and enhancing the product within the DCRI.
The Business Value of the Clinical Trial
Management System
We have officially been using the CTMS for a little over two years for
all new projects. Pre-CTMS, we were using two different programs
that had been written in-house to capture the same type of
information, both of which were in a production environment, and as
such it was difficult to support and build on the programs.
We started out by introducing CTMS in a couple of test projects in a
pilot phase. Once that was deemed successful, we rolled it out across
the organization, and since then all new projects have had to use
CTMS. In parallel, we initiated a project to identify all trials that were
using the previous programs and, with the aid of a specially designed
matrix, determined the ones that were candidates for migration to
CTMS. Some projects were left to simply run out their life-cycle within
the old system, while we actively migrated others—at least 10
projects—to CTMS. We are now at a point where we are 100% using
CTMS, and the previous tools have been retired.
With the one, holistic product we now have a much higher competency
center, so if end-users have issues they call my team and we are able to
answer their questions. Furthermore, within the clinical operations
organization, because everyone is using the same product you can get
immediate help from the person sitting next to you. There are five
distinct areas where the CTMS has provided benefits to the DCRI.
Single Source of Information
The CTMS is our single source of all trial information relating to site
management and monitoring, and is useful in helping us get an
understanding of how long it takes for sites to become active and to
start enrollment. Once enrollment is under way the system can also help
us keep track of enrollment trends, how sites have performed, and how
we have performed in reaching enrollment goals.
Such historical information is crucial for successful future trial planning.
When the DCRI is starting up a new study with specified parameters, it
is important that my team is able to provide the data that make it
possible to compare the new study with similar trials that have already
been completed. Timing is the hardest thing to factor in, as it is so
variable among trials. There are large and small trials, long and short
trials; some trials run fairly close to schedule, while some undergo a
change in scope that causes them to run over time. Trying to make sense
of all of the data is a very complex job. It has been made easier with the
advent of CTMS because we can query the data, filter them, and then
receive a report. Previously, we would run a series of separate reports,
which were then combined in a spreadsheet for manual analysis.
Standardization
One of the strengths of the product is that it allows us to implement
a standard framework, yet in some areas there is an inherent flexibility
that we can customize for each trial. Therefore, we can have a
standard framework for the whole organization, yet still be able to
cope with the unique aspects presented by each trial.
The functionality across the trials is fundamentally the same: we can track
sites, track milestones within sites, create conversation logs for the sites,
record site visits, and make trip reports. Where the flexibility comes in is
that with certain trials we may want, for instance, five milestones, while
Clinical Trial Management Systems in the Wild
Kevin Jarrell is a Project Leader for the Duke ClinicalResearch Institute’s (DCRI’s) clinical trial managementsystem (CTMS). He joined the DCRI in 2007, and sincejoining the CTMS team he has led several successfulmajor and minor releases/upgrades to CTMS. In additionto managing the day-to-day support team, he is activelyplanning future development to align with the strategicdirection of the DCRI. Mr Jarrell started his career as aLaboratory Technologist in the genetics laboratory of a
major central laboratory. He then changed industries and began working at a majorclinical research organization as a Clinical Research Associate and Clinical Trainer, beforeswitching departments to become a Senior Information Technology Business Analyst,focusing on improving the company’s CTMS. He received a BSc in biology from LongwoodCollege, Farmville, Virginia.
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for another trial we may want 10, and for a third trial we may require 30.
Moreover, one trial may need conversation logs while others do not.
Similarly, we can specify the number of documents required per trial, and
so on. Essentially, for each trial we can determine how much or how little
of each item it needs or the trial team wants to use. Of course,
standardization—for example standard terminology and definitions—
sometimes brings its own restrictions. There are always rare examples
where one particular group will need something very different from the
norm, and that is always a challenge. It is a balancing act, trying to meet
the needs of the 90% without excluding the needs of the 10%.
Regular Upgrades
With the CTMS platform, we have been able to structure our software
development life-cycle in such a way that we can put out new
functionality every three to four months. This means that if the end-
users identify something they would like to change, we are able to
turn that around fairly quickly and get their enhancement request back
to them. There have been elements that the product has not provided
that we have added in. For instance, we have done a lot of work
around our trip reports, including adding the capability for electronic
signatures and adding new sections of information. We have also
added fields to existing data components or pick lists and segregated
data so that only certain users can see them. While this is implicit in
the role-based security that the system offers, we have also added
extra security.
Accounting for Cost
The labor costs in terms of running and maintaining CTMS are treated
as an infrastructure expense. Now that we have implemented the
product, we are in the maintenance and ongoing enhancement mode.
This means that for development, as we follow the software
development life-cycle, we do not have to go back to the Technology
Steering Committee and request more funds. We are able to dedicate
staff to the CTMS product and continue to build or enhance it. Using
this structure, we have been able to build up the product very quickly.
Targeted User Groups
For each new release or upgrade we try to target a primary user group.
While there may be other enhancements that may fit the needs of
many other groups, from our perspective the best way to implement
an upgrade is to focus mainly on just one user group and deliver
something significant to them.
At the DCRI there are various user groups, including those that deal with
site management, site monitoring, safety, and data management;
groups that are responsible for business administration and liaising with
sponsors; a management team that runs the clinical operations
organization; a contracts group; and a group that deals with the
regulatory side.
Enhanced Efficiency
The main savings we have realized using CTMS have been in terms of
operational efficiency. The Siebel eClinical product is web-enabled,
and we have also made it HTTPS-secure so that our monitors can
access it from virtually anywhere. As a general rule, people are much
more accustomed to a web interface than to any bespoke program,
and the layout appears logical to them. Using a standard Internet
browser, users can access the system, enter data, run reports, and
obtain information, which was not possible before. The response time
is good, so it is possible to move around the system and enter data, as
well as generating reports, so that management can make decisions.
The major time savings we have seen so far have been around enabling
the decision-maker. Having a single place, standard definitions, and
standard ways to enter data, allowing all of the different trial team
members to put their data into one place, and then being able to run
reports on the data, have probably been the areas where we have seen
the greatest time savings and the most efficiency. Regardless of the
interface, it still takes a clinical research associate the same amount of
time to type up a trip report, and there is not a tremendous amount of
time saved regarding most of the day-to-day routine tasks. Nevertheless,
having a tool that users go to every day and become accustomed to and
proficient with in itself generates efficiency: if a task can be completed
more quickly, it frees up time to do something else.
Future Directions
The true benefit we have derived from this system is our ability to
configure it and customize it for our individual business needs. This
has allowed us to integrate and automate some aspects of our
business that are unique to us. This is the aspect that will occupy us
over the next couple of years: trying to ingrain CTMS into our business
and into our business processes, and in so doing further maximizing
our investment.
Having the eClinical product built around our business needs has
proved very supportive. We are mindful of what else we could do with
the extended functionality, and there are high-level discussions around
where our business could go, but we do not want to be in a position
where the software drives the business. Therefore, so far,
implementing CTMS has not changed our services.
Most of the advantages we have achieved are due to the good
collaborative working relationship we have at the DCRI between the
business and IT sides of the organization. Both sides are in alignment
in wanting to do the best we can for the organization, which is not
always the case. Working on a unifying project such as this has helped
cement that relationship, and will hopefully create new ones further
down the line. ■
It is a balancing act, trying to meet the
needs of the 90% without excluding
the needs of the 10%.
The major time savings we have
seen so far have been around enabling
the decision-maker.
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a report by
Henry Levy
Senior Executive, Accenture
In the current climate, the biopharmaceutical industry is experiencing
unprecedented pressures on multiple fronts. Drug development costs
continue to spiral upwards, there is increasing generic competition,
pipelines are shrinking, and there are pricing pressures from healthcare
providers. So, it is no surprise that the industry watchwords in these
turbulent times are efficiency, accountability, and control. Based on its
experience, Accenture believes that biopharmaceutical companies on the
path to achieving high performance not only need to keep costs contained
but also need to ensure accountability of expenditure. Thus, more
companies are embracing technological solutions to help manage their
portfolio of developmental projects as well as to execute their clinical trials
in an efficient and controlled manner. This article discusses some of the
major information technology (IT) trends that have affected and will
continue to affect the biopharmaceutical world, and examines the role of
clinical trial management systems (CTMS) within this environment.
Industry Trends
The number of industry-sponsored clinical trials has been steadily rising in
recent years. Investigational New Drug submissions at the US Food and Drug
Administration (FDA) have increased from 542 in 2004 to 662 in 2007—a
22% increase.1 Not only are there more trials today, but there is also a trend
of an increasing number of patients per trial. Trials are also becoming more
complex and require a higher statistical power to prove safety, specifically in
those areas where new products are targeted to major populations.
Coupled with the related trend for the biopharmaceutical industry to tackle
more novel, multifactorial diseases, this all points to trials of greater
complexity and longer duration. Furthermore, FDA figures show that the
number of new drug approvals has been in general decline since the mid-
1990s: only 18 innovative new drugs were approved in 2007 (see Figure 1).
Micro Trends
Paradoxically, for an industry that is often at the forefront of scientific
discoveries, the biopharmaceutical sector in general has been a slow
adopter of new IT. Electronic data capture (EDC) technology began to be
implemented nearly two decades ago. From these early beginnings, it
was expected that clinical trial data collection and management would
rapidly evolve from a paper-based system to an electronic environment,
with more than 50% of trials being performed using EDC within two to
three years. The reality is that, due to several factors, progress has been
very slow, and it is only in the last two years that Accenture has seen the
true adoption of the new model for data acquisition and management.
Many in the biopharmaceutical industry can now see the value and
importance of effective IT and how it can help drive high performance in
an organization. However, the need to invest significant capital in
enabling software or technology has been another major barrier to the
implementation of effective IT initiatives. To overcome this obstacle there
has been a shift away from large single capital investments—often in
the range of $20–30 million—toward making IT investment part of the
annual expenditure budget. Companies now look to purchase software
or technology using different financial models that have had a significant
impact on the application landscape. Application service provider models,
or one-time/per-study/per-site contracting, are examples of these flexible
approaches to financing clinical trial technology. We have seen how
these new models allow biopharmaceutical companies to regulate cash
flow and, critically, to significantly reduce large capital investments. The
biopharmaceutical companies are still, in effect, making the same
investment in terms of overall expenditure, but the new models give
companies flexibility in their overall budgeting process and, importantly,
are reflected in the figures that are presented to the financial markets.
Macro Trends
On the macro level, there has been a major change within the industry in
the way in which biopharmaceutical companies regard R&D. In previous
decades, the early research phases were perceived purely as a means to
generate innovation and create pipelines. With the considerable decline of
productivity across the pharmaceutical industry, coupled with a near two-
fold increase in spending over the last seven years (see Figure 1), it has
become essential that R&D be managed with a business-like approach.
Effective clinical trial management and operational efficiency need to be
at the forefront of clinical operations organizations.
Consequently, R&D is, for the first time, being held accountable for its
budget. It is critical for R&D to cut costs while delivering the same (or
greater) number of trials. The heads of R&D of many biopharmaceutical
companies have been asked for $100–300 million in cost reductions to
contribute to $1–2 billion cost-cutting objectives for the whole
corporation. For example, Bristol-Myers Squibb began 2007 by promising
$600 million in cost savings, added another $1.5 billion in December
2007, and has recently added another $1 billion.2 Wyeth,3 Merck & Co,4
Pfizer,5 and Novartis6 have announced similar cuts in expenditures.
Technology as the Enabler of High Performance—The Place of Clinical Trial Management Systems
Henry Levy is a senior executive with Accenture, based inthe US. He is a member of the leadership team forAccenture’s global Life Sciences Research and Development(R&D) practice, where he leads the portfolio of global R&Dbusiness and system integration projects. His primary focusfor the last 14 years has been clinical development, and his expertise ranges from defining clinical developmentstrategies to implementation of enabling systems, as well asdeployment of outsourcing services to support key
development processes. Mr Levy speaks regularly at global conferences on a broad range oftopics, including new paradigms in clinical development, impact of data integration in thedevelopment process, and IT landscape and future trends in R&D. He is a recognized thoughtleader in these areas.
Accenture realizes that the trends discussed previously will have an
impact on the R&D activities of biopharmaceutical firms. One major effect
will be rationalization—of pipelines, clinical trials, and patients. At the
highest level, this rationalization will result in a reduction in the number
of trials: companies will have to decide what the focus of their pipeline is
and make some difficult decisions about which trials to conduct.
Adaptive trial design will come to the fore as it will allow companies to
reach a ‘kill’ decision regarding trials more quickly, and can also help
optimize ongoing clinical trials.
We also anticipate that companies will reduce the number of trials run in
parallel for a single product. For example, a company with an oncology
drug that had shown promise in treating both head and neck cancer and
pancreatic cancer would previously have tested the candidate drug in
both indications at the same time. The strategy now is to focus: pursue
the indication that either has the best chance of obtaining approval or
that will recognize the best value. Obtaining a first approval improves the
likelihood of getting subsequent approvals.
The trends will also promote outsourcing, specifically the need to define
new models for optimizing resources in India, China, and Eastern Europe.
Outsourcing can potentially achieve a 30–40% reduction in the cost of
non-core components such as clinical data management, document
management, IT, and application management, and can even reduce
certain costs related to pharmacovigilance and regulatory submissions.
Depending on the company, between 3 and 7% of R&D costs may reflect
such non-core elements.
Crucial Drivers
For biopharmaceutical companies to meet the objectives of increasing
clinical trial throughput and reducing costs, Accenture sees the need for
improvement on several fronts, including control, operational efficiency—
with a goal of reaching operational excellence—and better decision-
making. Clinical trial management technologies play a central role in
providing these capabilities to evolving development organizations.
Control
Go to any biopharmaceutical company today and ask the question: In
each therapeutic area, how many trials are you running, and how many
are in phase I, phase II, phase III, or phase IV? Typically, nine out of 10
companies would take several days to collect and provide that
information, and in most cases the data would be inaccurate. The data
may be late or out of date, or based on information derived from strategic
plans rather than from actual executed plans. This problem is endemic and
can be seen at multiple levels: the number of sites that a company has
active at any one time, the number of qualified investigators available to
conduct the trials, the number of required certified laboratories—
essentially anything related to control over the clinical trial portfolio. These
discrepancies can represent organizational, technological, local, or global
issues. A company may have control over individual pieces of the clinical
trial process, but not consistent and comprehensive control—and without
that the company lacks the ability to manage its resources effectively.
The need for control is a principal reason for implementing a CTMS such
as the Siebel Clinical from Oracle. Siebel Clinical’s origins in sales force
automation and customer relationship management provide flexibility in
helping companies manage different types of trial. This kind of highly
customizable, highly configurable CTMS—one that is able to manage
different types of environment, from pre-marketing trials to phase IV
post-marketing studies or country-specific accounts—offers a control
system that can effectively manage disparate resources.
Operational Excellence
Operational efficiency—with the ultimate goal of operational excellence—
is essential for proper execution of clinical trials. Achieving operational
excellence requires a clear plan and knowledge of both the critical
milestones and the relevant dependencies. Effective management of a
project as complex as a clinical trial requires access to accurate reports that
detail the daily status of patient enrollment, updates on how much new
data has been gathered and cleaned, key dependencies on regulatory
approvals at the site, and the status of payments to the investigator site.
With this information, the heads of clinical development can develop an
understanding of their workload within the context of their whole trial
portfolio and manage their trial and submissions timelines effectively. With
proper resource and project management capabilities, the development
organization is able to manage its resources effectively and nimbly
reallocate resources as projects are cancelled or as priorities change.
Decision-making
Accenture believes that data analytics can add significant value to
improving or optimizing decision-making, while also making the decision-
making process more strategic. Taking advantage of current and
historical data allows a development manager to be more proactive;
through modeling and simulation he or she can predict the success of
upcoming trials and therefore adjust, in advance, either the design of the
trial or the method by which it is executed to reach the optimal level of
performance. This predictive capability is achieved by examining the data
from, for example, the performance of one investigator over the last five
years, combined with knowledge about the relationship between the
clinical trial sponsor and that investigator. In addition, historical site-
performance data across enrollment, quality of data delivered,
compliance, and specific patient populations can increase the success
rates of a site in a clinical trial. As we look forward, we see that coupling
Figure 1: Research and Development Spend versus New Drug Approvals
Data courtesy of Pharmalicensing. Sources: Burrill & Co, Biotech 2007 Life Sciences: A GlobalTransformation, PhRMA Annual Membership Survey, 2008; fda.govNME = new molecular entity.
0
5
10
15
20
25
30
35
40
2001 2002 2003 2004 2005 2006 2007
Total NMEs
No
of N
MEs
R&D
spen
d $b
n
R&D spend (PhRMA members)
0
5
10
15
20
25
30
35
40
45
50
Levy_edit_subbed.qxp 9/12/08 2:06 pm Page 15
16 E C L I N I C A L V I S I O N S
High Performance The Place of CTMS
of this existing information with new sources such as payer or
prescription data can further improve trial execution.
Within a CTMS, a pre-defined analytics data model coupled with a
supporting technology platform for mining complex data are now critical
parts of the decision-making process for system selections and are key
differentiators for those vendors that can provide an off-the-shelf
analytics capability.
Critical Factors for Achieving High Performance
Even after selecting an appropriate CTMS vendor, companies face many
pitfalls that can cause delay, increase costs, influence adoption, and,
sometimes, lead to failed projects. Critical factors related to avoiding
these pitfalls and achieving high performance include the ability to
manage scope and avoid excessive customization, and avoiding the
overintegration of CTMS capabilities with point-to-point interfaces rather
than leveraging a service-oriented architecture. However, the most
common reasons for suboptimal implementation of CTMS solutions
relate to a lack of balance between system implementation and process
or organizational change during the implementation, and to poor
adoption and lack of quality data after roll-out.
Business Integration versus Systems Integration
Implementing a CTMS is never a solution in and of itself. Appropriate
processes and the right organizational support model must be in place if
the technology is to truly enable high performance. In successful
implementations the focus is on business integration, not just systems
integration. Achieving high performance starts with determining business
needs and its current processes, identifying the appropriate operating
model, and then using technology as an enabler, not as the main solution.
The complexities of data analytics mean that there is more to the process
than simply gathering and manipulating vast quantities of data. Many
companies gather and store large amounts of data, yet use only 5–10%
of this valuable database. This is a huge investment in data that will never
be used. Accenture believes that, in order to achieve a ‘higher state of
awareness,’ companies must do more than simply experiment with
techniques and hope for a positive end result. Biopharmaceutical
companies must understand good methodology in terms of data
analytics: to observe what is happening, make a determination, develop
theories, and then understand what the actual questions are that must
be answered. This type of fundamental scientific thinking is critical before
data analytics can be utilized effectively. By starting with the question to
be answered before collating the actual data and performing meaningful
analytics, companies can create a feedback loop that might allow for the
discovery of some of the unknowns in the equation.
How to Keep Good Data
One of the biggest challenges companies face when installing a new
system is ensuring the migration and maintenance of good, clean,
up-to-date, quality data. This is a particular problem for larger
biopharmaceutical companies with vast amounts of legacy data. An
investigator database at any company potentially contains as many as
10–20% duplicate entries. This inability to distinguish whether the data
are clean will hamper new implementations, or at least significantly
decrease the value of them. Keeping good data requires intervention.
This can be achieved by providing appropriate data visibility to multiple
layers of the host organization, including development leaders. Similarly,
exposing the data to sites accessible through investigator portals can
stimulate compliance with data quality initiatives.
Future Perspectives
Accenture recognizes that the main challenge now facing
biopharmaceutical firms is how to do more—or at least the same—with
less, which entails driving productivity and reducing costs. Therefore,
maximizing the value of data, including clinical and trial management
data, will be a critical part of development organizations’ objectives. At
the top of the agenda for all R&D leaders who seek high performance is
development and enforcement of discipline concerning effective data
capture, maintenance, and analysis. This will enable decision-makers to
more effectively influence clinical trial design and strategic direction while
taking a drug through the approval process.
Current trial management and data analytics systems can provide
companies with effective platforms for achieving better utilization of
data. However, companies who seek to be high-performance businesses
must also adapt their organizations and their cultures to take full
advantage of the capabilities available to them, allowing them to be
more competitive in the increasingly challenging and complex
environment of the pharmaceutical future. ■
For more information on how Accenture can help you achieve high
performance, contact Henry Levy at +1 267 216 1827 or
