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HEALTH SCIENCES
eClinical Visions
BRIEFINGS
Clinical Trial Management: Enabling Operational Efficiency
Contents: New Challenges Call for Innovative Approaches Rachel Yang, Oracle Health Sciences
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
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ECLINICAL VISIONS
BRIEFINGS
CLINICAL TRIAL MANAGEMENT: ENABLING OPERATIONAL EFFICIENCY Editorial Managing Editor Michelle Grayson Technical Editors Dr Patrick Wong Claire Thomas Sub-editorial Manager Claire Dunn
Operations Associate Director—Operations Tim Green Designer Christian Fanslau
Business Development Associate Director—Bespoke Publications David Ramsey
Editorial Contact Michelle Grayson T: +44 (0) 20 7452 5181 F: +44 (0) 20 7452 5050 E:
[email protected]
In association with:
Operations Contact Tim Green T: +44 (0) 20 7452 5023 F: +44 (0) 20 7452 5610 E:
[email protected]
HEALTH SCIENCES
Business Development Contact David Ramsey T: +44 (0) 20 7452 5152 F: +44 (0) 20 7452 5606 E:
[email protected] Touch Briefings is the trading name of Business Briefings Ltd, a Touch Group plc company All information obtained by Business Briefings Ltd and each of the contributors from various sources is as current and accurate as possible. However, due to human or mechanical errors, Business Briefings Ltd and the contributors cannot guarantee the accuracy, adequacy or completeness of any information, and cannot be held responsible for any errors or omissions, or for the results obtained from the use thereof.
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Contents
ECLINICAL VISIONS CLINICAL TRIAL MANAGEMENT: ENABLING OPERATIONAL EFFICIENCY Introduction New Challenges Call for Innovative Approaches
3
Rachel Yang , MD , PhD Director, Product Strategy, Oracle Health Sciences Global Business Unit
eClinical Visions Implementation of a Clinical Management Technology System
6
Jennifer Hunt Senior Director, Clinical Research, Genzyme Corp.
Clinical Trials Management of the Future
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Michelle Grayson 1 and Claire Thomas 1 with contributions from J e a n n i e I n g e 2 and J a s o n P a c k w o o d 3 1. Touch Briefings; 2. Vice President for Information Technology, PRA International; 3. Vice President for Business Solutions, PRA International
Clinical Trial Management Systems in the Wild
12
Kevin Jarrell Project Leader, Duke Clinical Research Institute
Technology as the Enabler of High Performance— The Place of Clinical Trial Management Systems
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Henry Levy Senior Executive, Accenture
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Introduction
New Challenges Call for Innovative Approaches
a report by
Rachel Yang, MD, PhD Director, Product Strategy, Oracle Health Sciences Global Business Unit
The way the biopharmaceutical industry conducts clinical trials is
the access control necessary for the clinical trial industry, as well as tools
undergoing a remarkable transformation. Coupled with this much-
that significantly reduce the administrative overhead.
needed evolution are new challenges specific to the increasing role that information technology will play to enable the new clinical
The globalization of clinical trials needs to be truly worldwide rather than
development landscape.
just a process of more trials conducted in different locations. This will require global unified systems with built-in functionality that supports
Of the many challenges facing the biopharmaceutical industry today, the
specific regional needs. The current mindset, however, is still more or less
critical need for greater operational efficiency in clinical drug
focused toward the traditional North America/Western Europe
development is paramount. With flat and even declining productivity,
requirements and supporting prevailing business needs. For a truly global
rising research and development (R&D) costs, more complex pre-
system, this view needs to change to ensure individuals and departments
approval trials and large post-approval studies driven by the shift toward
have an understanding of where they fit into the business process. Regional
biological agents, and increasing regulatory demands, it is essential that
units need to understand how their work affects others in the process so
clinical trials are managed more effectively and efficiently. While
that effective collaboration can take place. It is also important to assess the
progress has been made in addressing these challenges, companies are
impact or implication that local infrastructure and culture might have on
increasingly turning to clinical trial management systems (CTMS) to
conducting clinical trials in developing countries. Understanding the local
improve trial efficiencies, cut trial costs, and enhance the productivity
environment and requirements often drives innovation that brings about
of trial participants.
substantial impact. Innovative solutions that are very site-focused, very pragmatic, and very specific to the local infrastructure may overcome
The Globalization of Clinical Trials
barriers. For example, patient follow-up is a significant issue in China. A
The global clinical trial, while not new to either sponsors or clinical
large Chinese CRO has proposed utilizing mobile technology, in the form
research organizations (CROs), is becoming more prevalent. Clinical trials
of cell phones, as a component of its site management system. The
are increasing in size and complexity and more global trials are being
proposed system would allow stakeholders to send the alerts or messages
conducted with sites across diverse geographical regions. The predicted
via SMS, or push reminders to patients regarding visits. This form of
trend is that there will be a significant shift from North America/Western
collaborative tool, along with better data visibility, will help clinical research
Europe to the Asia-Pacific region (APAC). Between 2008 and 2010 the
associates (CRAs) better manage their sites and increase study compliance.
percentage of trials conducted in North America/Western Europe is expected to fall from 55 to 38% (see Figure 1).1 Clinical trials conducted
Increased Outsourcing of Clinical Trials
in APAC countries offer potential cost savings as well as large patient
It is estimated that 20% of the biopharmaceutical industry’s R&D
populations, particularly of treatment-naïve patients. This shift will also
spend is on outsourcing. Coupled with the increasing globalization of
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
Rachel Yang, MD, PhD, is Director of Product Strategy at Oracle Health Sciences Global Business Unit. She joined Siebel Systems in June 2000 as a Product Manager to lead the development of a new clinical trial management system (CTMS). Working closely with life sciences customers and partners around the world, she was instrumental in developing 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, and Pharmaceutical 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 providing strategic directions on Oracle’s clinical trial management solution for the life sciences industry. Prior to joining Siebel Systems, she worked at PPD in various capacities. She is listed as 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 scholarship from the University of Virginia at Charlottesville to study yeast genetics and molecular cell biology, where she earned a PhD from the Department of Microbiology. E:
[email protected]
appropriate files. Fortunately, technology solutions exist that provide
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Introduction allow both pre-marketing and post-marketing safety data to be viewed
Figure 1: Geographical Distribution of Clinical Trials
holistically and longitudinally will become increasingly necessary. 10%
Eastern Europe
eClinical Adoption Drives Systems Integration and
2006 2010
13%
Support of Cross-application Business Processes Electronic data capture (EDC) is taking hold and significant progress has
3%
Rest of Asia
been made in the last decade in terms of leveraging EDC and other 5%
eclinical technologies in conducting clinical trials. Consequently, subject enrollment information no longer comes in the form of faxed enrollment
3% India
logs. Rather, it often comes from interactive voice response systems
5%
(IVRS) or EDC. This means that CRAs can obtain strategic information about a trial’s progress and case report form (CRF) information during a
4% China
trial without having to travel to the site.
7%
Therefore, CTMS is no longer the system of entry for many such data, yet
7%
Middle East and Africa
to get a clear picture of study conduct, view actual patient enrollment
14%
against plan, track actual payments against budget, and forecast workload and resources needs, it is imperative for CTMS to have accurate
15%
Central and South America
data on information such as patient enrollment as well as CRF
11%
completion. Manually entering data into CTMS after they have been entered into other systems is highly undesirable since it is labor-intensive
25%
Western Europe
and error-prone and requires costly conflict resolutions. Thus, integration
19%
with other systems becomes necessary. 30%
North America
Vendors who have built products/applications on standard-based open
19%
architecture offer compelling value in assisting biopharmaceutical 0%
5%
10%
15%
Adapted from McDonnell & Mooraj, AMR Research.
20%
25%
30%
35%
1
companies in their integration efforts. Service-oriented architecture (SOA) offers a new way to build open applications that can be shared by common processes across multiple applications. SOA essentially breaks
clinical trials, the cumulative result is a need for greater sharing of
down the traditional barriers between systems by providing a common
information between all stakeholders. Among CROs, sponsors, central
platform on which to build solutions that can be shared as interoperable
laboratories, and other participating service providers, the need for
services. Oracle is leading the effort to develop next-generation SOA-
increased data sharing is inevitable. CTMS that are built on open
based applications for the clinical industry. These will provide better
architecture and facilitate data exchange with third-party applications
support for business processes that span multiple applications, and will
bring significant cost savings to biopharmaceutical companies and
reduce the need for costly point-to-point integration.
CROs. Increased outsourcing also means that biopharmaceutical companies will likely work more with different CROs in the future, and
Declining Number of Investigators and a
vice versa. Thus, having a flexible CTMS that can be easily modified as
Limited Number of Trial Sites
business needs change offers long-term benefits to biopharmaceutical
Tufts reports a continuing decline in the number of US investigators.
companies and CROs.
Moreover, there has been an increased use of first-time investigators, with 50% of investigators never conducting a second trial. This issue of
Growing Demand for Post-marketing Studies
poor investigator retention, especially in the US, is a major challenge.
Another recent trend is the growing demand from regulatory agencies in
Investigator recruitment and retention remains one of the most
the US, Europe, and Japan for large-scale post-marketing studies as a
important aspects of clinical trials. Poor retention rates suggest that there
condition for approval. Indeed, according to Tufts, between 1998 and
is a need to innovate the approaches currently used to identify and target
2008 75% of new drugs approved in the US and the EU, and 50% of
suitable investigators, and to retain good investigators.
those approved in Japan, had post-marketing study commitments attached to the approvals.2 Post-marketing studies are typically much
Biopharmaceutical companies need to build stronger, more personalized
larger in scale, with hundreds or even thousands of sites and many more
relationships with investigators to foster loyalty. Investigator loyalty gives
patients. Managing large-scale trials carries unique challenges. While
biopharmaceutical companies a strong competitive advantage. There are
pre-marketing studies focus on data quality for each individual patient,
several strategies that biopharmaceutical companies can use to
post-marketing studies place greater emphasis on sampling and
strengthen the relationships with their investigators: by providing the
automation. CTMS that have built-in workflows that can be easily set up
necessary information at their fingertips with easy-to-use productivity
and modified are well suited to the rigors of post-marketing studies.
tools that make conducting clinical trials less time- and resourceconsuming, by paying investigators quickly and accurately, etc.
The greater focus on safety monitoring and pharmacovigilance also
Fortunately, leading CTMS vendors have adopted a customer
means that CTMS that support both pre- and post-approval clinical trials
relationship management paradigm and methodology and developed
offer distinct advantages. Integration with safety surveillance systems that
robust features to allow companies do just that. By assisting
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New Challenges Call for Innovative Approaches
investigators and providing them with the best possible trial experience,
The Reality Now and Looking to the Future
individual companies set themselves apart from their peers and see
Increasing globalization of clinical trials, driven by the need to lower costs
improvement on investigator retention.
and recruit participants; greater outsourcing; more complex trials and postmarketing studies. These are just some of challenges facing the
As more companies conduct EDC trials, investigators are required to enter
biopharmaceutical industry. Many of these issues can be addressed to some
data directly into each company’s EDC systems. For those who are
degree with currently available IT technology. However, as the technology
performing multiple EDC trials, this often means having to log on to
evolves, it will sustain and drive forward the eclinical vision. Collaboration
multiple different systems, or even carry several laptops. There are also
tools that make all participants in clinical trials more productive can only be
CTMS portals that provide useful trial information as well as differentiated
beneficial, and robust CTMS solutions that are built to support business
services to investigators. While each of these applications has a unique
processes instead of focusing on collecting data will come to the fore.
value, the challenge for the industry is to come up with a holistic approach and build solutions on a common technology platform that addresses the
For this publication, we have received contributions from experts within
clinical trial needs of investigator sites. This is also why it is so important
and supportive of the biopharmaceutical industry. These experts talk
for the technology industry to work closely with regulatory agencies and
about their overall views of the future of clinical trials and the process of
standards bodies such as the Clinical Data Interchange Standards
implementing a CTMS that not only helps their day-to-day job but also
Consortium (CDISC), SAFE, and the Clinical Research Information
brings efficiency to their organizations.
Exchange (CRIX). A greater culture of collaboration, with crossgovernment and cross-industry initiatives that look at the business process
Jennifer Hunt, Genzyme, describes the thought processes engaged and
in terms of addressing needs rather than from the traditional multiple
the procedures followed when Genzyme set out to search for a CTMS.
platforms from multiple vendors aspect, will help to streamline the process
The dual aims of the quest were to contain trial costs and provide insight
and create greater efficiency.
into study progress across the entire organization. The resultant CTMS system, while still very much a work in progress, is slowly becoming the
Adaptive Trials—A Reality of Clinical Trial Evolution
authoritative source for clinical trial information at Genzyme.
Adaptive trials will become a reality or even a necessity rather than just a concept. Regulatory agencies in the major markets have implemented
Kevin Jarrell, Duke Clinical Research Institute (DCRI), shares with us the
evolving positions on adaptive clinical trial design, and information
business benefits of implementing a CTMS. It has been customized to suit
technology (IT) vendors are developing software to support adaptive
the particular needs of DCRI as an academic research organization, and
designs. Adaptive design uses accumulating data to decide how to
has empowered the decision-makers and encouraged collaborative
modify aspects of the study so that the right development questions
working across the whole organization.
can be answered more efficiently and accurately without undermining the validity and integrity of the trial. Adaptive design also provides
Jeannie Inge and Jason Packwood, PRA International, illustrate how a
patients participating in a trial with a greater probability of being
forward-looking company can embark on a technology expedition and
allocated to treatment that works than in a traditionally designed trial.
use IT creatively to improve operational efficiency, optimize decision-
Much of the focus has been on statistical design of adaptive trials and
making, and contain costs. PRA’s CTMS has allowed the CRO to steadily
impact on patient data capture, while very little has been done in terms
grow its client base, its geographical footprint, and the size and
of supporting adaptive trials from the trial management and
complexity of the clinical trials it runs.
operational perspectives. Traditionally, a study is set up when just about every step has been properly mapped out in a study protocol.
Henry Levy, Accenture, describes technology as an enabler of high
Adaptive trials challenge the traditional model and call for greater
performance. He outlines Accenture’s view of macro and micro trends in
flexibility on study set-up, site set-up, study design, and patient
the biopharmaceutical industry and how these will help drive faster
enrollment. Unfortunately, many current CTMS are built for the
technology adoption. For companies that seek to employ technologies in
traditional clinical design, and only a very few CTMS vendors have
general—and CTMS in particular—it is not enough to simply ‘plug and
started building functionalities that provide the flexibility for adaptive
play’; firms must adapt their organization to take full advantage of the
trial designs.
technologies and improve their business.
One adaptive element that is not talked about in the context of
We are grateful to our authors and contributors for their insights, and
adaptive trials is the ability to ‘adapt’ and modify how trials should be
trust you will find their experiences and views relevant and enlightening.
‘executed’ rather than ‘designed’ based on realtime information
Looking ahead, Oracle sees great opportunities to help the
available on the study progress. Embedding analytics solutions in
biopharmaceutical industry re-energize drug development by providing
clinical applications transforms applications such as CTMS and clinical
innovative technologies. Oracle’s vision is to provide a set of integrated
data management systems (CDMS) from being places where data are
clinical trial solutions that is SOA-based and built on standard middleware
simply entered and stored to places where business intelligence is
technology with integrated business intelligence, and can be offered as
gained and actionable insights are generated by and for the end-users.
‘software as service.’
Embedded business intelligence will not only enhance the value of clinical systems, but also help drive end-user adoption.
1.
McDonnell W, Mooraj H, Clinical Trials Are Moving Out, May 13, 2008. Available at: www.amrresearch.com
ECLINICAL VISIONS
2.
We look forward to your thoughts and feedback. ■
Postmarketing studies are becoming the norm in U.S., Europe, and Japan, Tufts CSDD Impact Report, 2008;10(4).
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Implementation of a CTMS
Implementation of a Clinical Management Technology System
a report by
Jennifer Hunt Senior Director, Clinical Research, Genzyme Corp.
There are many benefits to be realized from having a clinical trial
Contemplating Clinical Trial Management Systems
management system (CTMS). It acts as a central repository for all best
Genzyme initially had a system that had been built in-house by the Data
practices and company-specific information, as well as providing a way
Management group, which fulfilled that group’s needs very well: it could
to control and streamline clinical operations. This article will explore
track case report forms (CRFs) and data clarification forms and manage
the process of selecting, deploying, and maintaining a CTMS within an
workload. However, attempts to build in functionality, such as that found
international biopharmaceutical firm, highlighting issues and
in a CTMS, to help the Clinical Research department were not successful.
unexpected benefits that have been encountered along the way.
As a result, people within Clinical Research did not use it. Thus, primarily through the use of spreadsheets, each team developed its own solution.
Genzyme is a biopharmaceutical company that has grown from a small Boston-based start-up in 1981 into a global diversified enterprise
The current CTMS effort began in 2004, with basic discussions around
employing more than 10,000 people. Having started as a specialist in
containing costs and getting more insight into study progress across all
ultra-orphan indications of rare genetic diseases, Genzyme now has
of the therapeutic areas. There was a need to create efficiencies by
several different clinical groups, focusing on lysosomal storage
looking at best practices, centralizing all information about the
disorders, oncology, orthopaedics/biosurgery, transplant/immune
studies, and providing a tool for clinical users to help manage their
diseases, and renal, as well as a genetics/diagnostics group. As a way
daily operational activities. It was a long process, and everyone
to help facilitate the conduct of its clinical trials and provide support
involved from Genzyme was fully allocated to project work in addition
for the tools and resources across all of the therapeutic areas for the
to being part of this initiative. However, there was a common passion
company globally, in early 2008 Genzyme established a Global Clinical
directed toward realizing operational improvements.
Operations department. Having engaged a consultant to come in and help with the process of Typically, for the majority of its clinical trials Genzyme performs its own
selecting a system, the next step was to define Genzyme’s requirements
project management, particularly for the ultra-orphan indications that
and needs from a CTMS. It was also important to examine the most
require highly specialized knowledge. For most indications, the
crucial standard operating procedures (SOPs), breaking them down into
company also employs external monitors (clinical research associates
process maps to see where a CTMS could be utilized to automate
[CRAs]) to provide flexibility in recruiting monitors across the
the process. Only once this had been done was it worth looking at the
geographies. Whether internal or external, CRAs travel to study
different CTMS options available and matching them up with
locations and ensure that the investigators and institutions are
Genzyme’s needs. All of the top choices came in and presented.
adhering to good clinical practices (GCPs) and following the clinical study protocol, as well as checking that the subjects recruited meet the
Although the different systems had superficially very similar
criteria for the study and making sure that all of the regulatory
functionality, significant differences existed. The Siebel CTMS from
documents are in order. The study data are brought in-house and
Oracle has a sales history and therefore has a built-in concept of what
processed by Genzyme’s Data Management group.
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
Jennifer Hunt is Senior Director of Clinical Research at Genzyme Corp. Since joining Genzyme’s Clinical Research Department in 2001, she has worked on programs for ultra-orphan lysosomal storage disorders, before moving in early 2008 to the newly formed Global Clinical Operations Group. For most of her tenure, she was the global Biomedical and Regulatory Affairs team leader for Myozyme®, which was approved in 2006 to treat Pompe disease. 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, a biotechnology company focusing on xeno- and cell transplantation. She began her career as a Clinical Research Associate at Quintiles. Jennifer has a BSc in biology with a concentration in biotechnology from the State University of New York College of Environmental Science and Forestry at Syracuse, and an MSc in management from Lesley University.
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
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Implementation of a CTMS
Figure 1: New Clinical Trial Management System Users Created 90 80
70
Number of users
60
50
40
30
20
10 0 Dec 2006
Feb 2007
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
Jan 2008
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
that of other companies as Genzyme’s CTMS went live with the knowledge
studies. If someone is initiating a new program, he or she can contact
that, while the initial design was not perfect, sufficient useful functionality
Global Clinical Operations and get help in laying the foundation,
would drive end-user utilization, which in turn would create the helpful
including finding the resources, entering the protocols into the CTMS,
feedback for additional releases. This has proved to be the case, with an
retrieving the information, and any other technology needs.
increasing number of users adopting the system (see Figure 1). Within Global Clinical Operations is the Clinical Process and Technology One of the trade-offs is that the more customized a system is to meet
group, which manages the CTMS, including evaluating the use of
specific needs, the more of a challenge it can be to upgrade to the
electronic trial master files, dealing with reporting issues, planning for
next standard. While Siebel CTMS is highly configurable with the
studies, and helping people use the technology to make their jobs
Siebel Tools and provides full upgrade paths for configurations,
easier. There are also groups that focus on resourcing, contracts and
excessive customization is highly discouraged as it can make upgrades
vendors, study feasibility and subject recruitment, pharmacy-related
challenging. Judicious use of the Siebel Tools to configure the
issues, and, lastly, handling SOPs, best practices, and training.
application is the key, and in fact Genzyme has been able to keep configuration to less than 15%.
Learning the New System Having now implemented CTMS at Genzyme, there is an opportunity to
Organizational Linkages
reflect on the other in-house systems in order to identify clinical
Bringing in a CTMS creates waves. It is not an enclosed system: there
processes that do not currently have an effective tool and see whether
are many opportunities for integration with other systems and
the CTMS can help solve them. It has also been very helpful for Genzyme
opportunities to share data. Sometimes that will include taking a step
to become active with the extended Oracle user community. The system
back and determining the authoritative source: identifying the sole
is very flexible and different companies are using it in a variety of ways.
place within Genzyme where a data element is first entered, regardless
Communicating with other organizational users of Siebel CTMS is a
of system, and then sharing it. Doing this makes it possible to avoid
valuable strategy: it has allowed Genzyme to share its experiences and
redundancy and duplicative entry, which can lead to errors.
best practices with other firms, and vice versa. For example, one of these organizations is a pharmaceutical company that is much larger than
Similarly, along with unifying the data system, by creating the Global
Genzyme, and there have been periods of collaboration over the past
Clinical Operations group the hope is that the task of running this
two years that involve sharing non-confidential ideas about training and
system can be centralized. This will allow others in Clinical Research
system enhancements, often resulting in suggestions for improvements
more time to focus on conducting clinical trials. Global Clinical
that are then passed on to Oracle.
Operations can assume responsibility for not only executing CTMS but also looking to create synergies elsewhere as the company as a whole
Overall, adoption at Genzyme has been very good. People have been very
moves toward an even more global outlook: expanding into China and
pleased with the functionality. The CRAs, for example, have to create a
India, for example. It is important to be able to create consistency,
report after a site visit; previously this was written using a Microsoft Word
even while running studies in several geographies across different
template, but with the CTMS all of the templates and all of the questions
therapeutic areas in each of the business units. This group will help
are now in the system, making the process of reporting simpler and
move resources quickly and provide senior management with a
quicker. One of the main intentions of the system is to try to stop people
common understanding and insight into the progress of the clinical
from creating their own spreadsheets to track details about any given
development programs. It is also intended to be a resource for all new
study. A survey was conducted at Genzyme’s European headquarters in
ECLINICAL VISIONS
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Implementation of a CTMS Amsterdam that calculated how many spreadsheets people used before
Genzyme has seen benefits and cost savings since it started using
the implementation of CTMS compared with afterwards. Between April
CTMS; however, quantifying the cost savings remains a challenge.
and December 2007, there was a 20–40% decrease in the number of
Costs can be decreased in several ways: a task that used to take four
spreadsheets used, but not total elimination. However, instead of
hours to complete may take only two hours with CTMS; therefore,
banishing the spreadsheets, following the implementation of phase one
people can do more tasks. Alternatively, the actual external dollars now
the users in Clinical Research were asked what they were still tracking in
spent can be compared with former spend: for example, a CRA’s trip
spreadsheets, and as a consequence several pieces of functionality are
report would have previously been sent—signed with a wet signature—
being added in phase two.
by Federal Express; with CTMS, the approval process is completed electronically. The actual costs have not yet been calculated, although
Issues and Teething Problems
an administrative survey was carried out prior to the initial roll-out. This
The process of deployment and assessment has not only uncovered
survey addressed the time taken for common tasks; a re-administration
additional functionality to be added, but has also highlighted
of the survey will be able to assess any change.
unnecessary functionality that can be removed. This includes some requirements determined prior to system selection. One example is the
The Authoritative Source
ability to work and write reports within CTMS while users are offline.
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
By making CTMS the authoritative
CTMS. Thus, there needs to be a reporting tool to allow data retrieval,
source, people will not have to
is a high level of compliance.
but it is also vital to ensure that the data are accurate and that there
reinvent the wheel each time to deal In addition, terminology needs to be standardized so that protocols
with a specific problem.
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
This was considered useful for the CRAs who regularly travel across
consistent, technology-independent nomenclature overseen by one
the country and could not always connect to the Internet to access the
Genzyme-wide group. A word proposed for a new protocol status can
system. This capability enabled CRAs to have full access to CTMS
be posted centrally and assessed by all users. For example, the word
functionality without being connected to the Internet. The idea was
‘active’ when applied to a trial seemed ambiguous, and was changed
that CRAs would synchronize at least daily to upload all of their offline
to a status of ‘enrollment open.’ Once a decision such as this is made,
reports into the system and download any changes from the system.
the system is then manually cleaned up and made consistent.
While the remote capability did help CRAs be more productive while
Applying the highest standards possible to the CTMS has
on the road, it also brought some unanticipated challenges. For
encouraged other groups to ask whether they can pull data from
instance, if a contractor suddenly leaves the company with information
the system because it has become the authoritative source—the
stored in his or her computer, this weakens the system and raises a
first place that any piece of data will be entered. People from the
potential issue of confidentiality. If synchronization is not completed
business units use it to generate high-level reports about all of
frequently, data integrity and speed can be affected. After weighing
Genzyme’s programs. Furthermore, given the US Food and Drug
the pros and cons of enabling remote capability, Genzyme has now
Administration’s requirements for posting of clinical trials and results,
made a decision to disable the remote capability. Currently, Genzyme
this type of information can also be drawn from the CTMS by
issues wireless cards to certain staff who travel frequently so they can
Regulatory Affairs Compliance groups. Such groups will have
log on through a mobile telephone system, connecting through a
additional data requirements that can in turn be added to the system
private virtual network. In this way users are always securely
where appropriate.
connected to the live system and no data are stored on laptops. By making CTMS the authoritative source, people will not have to The ability to produce reports from the data contained within the
reinvent the wheel each time to deal with a specific problem. The
system has also taken time to develop. It would have been a very time-
CTMS can drive best practices and help establish a common agenda
consuming process to analyze and derive a top 10 list of reports in the
for a set of reports, allowing clinical professionals to focus on running
development phase. Therefore, an alternative is to allow ad hoc
studies and, ultimately, getting products approved. The process of
reporting, which will be released shortly. This will be monitored and
determining which system to install and how to use and maintain the
the data collected so that it is possible to determine which reports
system is a significant undertaking. Ultimately, successful adoption
work and which ones do not, and which ones are very popular and
should improve and streamline all functions within Genzyme and help
which ones less so. From the ad hoc reporting tool, a list of 20 or more
unite the different departments. A big part of the learning process
reports can be compiled and made available to all users in the system,
with CTMS is that simply installing a system is not sufficient to allow
removing the need to use ad hoc reporting and creating uniformity
declaration of success. There is much more work to be done to ensure
and speed.
that a CTMS is useful, and to achieve and maintain these goals. ■
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Clinical Trials Management of the Future a report by
M i c h e l l e G r a y s o n 1 and C l a i r e T h o m a s 1 with contributions from
J e a n n i e I n g e 2 and J a s o n P a c k w o o d 3 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
However, times are changing. Developments in Oracle’s systems have
pressure on a company’s ability to conduct them efficiently. This has
enabled CTMS to be offered at a lower cost than before, allowing more
led to the need for clinical development firms to implement new
companies access to the technology. Now, many companies are reliant
technologies such as clinical trial management systems (CTMS) to
on CTMS technology to manage numerous trials. With this reliance has
improve workflow efficiency. Furthermore, firms can maximize the
come the demand for information and ease of access to this information
potential of systems such as these by using them in innovative ways to
so that individuals can make rapid business decisions. This demand is
cut the time and costs required to take a drug through development.
what has necessitated pushing CTMS tools to a new level of performance, use, and scalability. In addition, the notion of transparency
Clinical
research
organization
(CRO)
PRA
International
has
between the client and CRO is paramount.
implemented some 20 enterprise systems in the last eight years. This article will discuss PRA’s experience with these systems, primarily
PRA’s experience using CTMS has been positive, and the key to that
CTMS, and how they have increased efficiency and reduced costs. It
success has been thinking ahead: the firm had been anticipating the
also describes how PRA has leveraged its current technology to meet
market and preparing its systems so that it could ‘slot’ a CTMS into the
new needs and how this bodes for the firm’s future. The article will
established business model. The company envisioned a 10-year plan
also look at ways to use CTMS to cope with changing trends and keep
(beginning in 1998) to create a standardized, robust, and scalable
pace with future developments in the field.
information technology (IT) infrastructure that is able to adapt as the business grows, taking on more and more complex trials. It has also
The Changing Face of Clinical Trials
proved important to develop a standardized network infrastructure, where
Over the last 10 years, PRA has seen its client base grow dramatically.
all employees across the world have the same hardware and software, to
It has gone from a company managing trials confined to one country,
avoid complications with maintenance as the company expands.
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
At the fundamental level of the technology plan are the enterprise systems
than 30 countries. As PRA has grown, the firm has had to adapt its
themselves, which comprise various applications (see page 10). All the data
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
Jeannie Inge is Vice President for Information Technology (IT) at PRA International, and is responsible for the global management of PRA’s technology and telecommunications infrastructure, application suites, and customer support. With more than 20 years of experience in business management, she has worked in marketing, business administration and accounting, training, and compliance. For the past 14 years she 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) (Siebel eClinical), and the Oracle adverse event reporting system (AERS), among other projects. She holds an MSc in information technology from the University of Virginia and is a certified Project Management Professional.
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
Jason Packwood is Vice President for Business Solutions at PRA International, spearheading various cross-functional system and process improvement initiatives for the company. He has been working in the biopharmaceutical industry for 15 years and has experience in clinical operations, information technology, application development, data management, and the 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 of electronic data capture (EDC) providers and the procurement process for identifying an in-house EDC solution: ClinPhone EDC. Today, he is the system owner for PRA’s CTMS (Siebel eClinical).
amounts of hardware and training, not to mention the license cost.
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Clinical Trials Management of the Future from here are stored in a data warehouse that can assemble the required
Prior to 2007, PRA compiled reports for monthly project status reviews by
information as necessary, allowing it to be viewed via the delivery portal.
collecting data from different systems and populating very complicated
The nuts and bolts of this infrastructure include a standardized IT solution
Excel spreadsheets. As well as encroaching on staff time—reports can
on Dell Hardware, Microsoft platforms, and, largely, Oracle databases. The
require around 600–700 different data points from many different
infrastructure is based on Cisco Networks, with AT&T being the global
functional areas—the company estimated that it was costing more than
provider. As noted previously, the company boasts the success of 20
$1 million to prepare these project metrics each year.
individual enterprise systems since 2000, all of which met project deadlines and budgets. Among these notable industry leaders include:
In order to start focusing on analyzing the information rather than preparing it, the firm tried to find a way to automate this process by
• Electronic Trial Master File System—a proprietary document management system based on Documentum;
leveraging its existing enterprise systems. Data warehousing technology is used to extract all of the data needed from systems such as Lawson
• Lawson ERP;
Financials, CTMS, and Oracle Clinical. These data are transformed into
• Siebel eClinical and Customer Relationship Management;
useable information compiled into a single report and delivered by
• Oracle Adverse Event Reporting System with E2B compliance;
PRA’s portal.
• ClinPhone EDC; • Siebel Analytics (OBIEE) for Data Warehousing;
Clinical Trial Management Systems for the Client
• Oracle Clinical and Remote Data Capture;
Despite all of the benefits of using CTMS, there can still be issues with
• Insight Publisher with eCTD Compliance;
user acceptance—the ‘what’s in it for me?’ problem. Does the system
• Cisco Enterprise Call Center;
provide the data that both the client and the PRA team need? The best
• Thermo Fisher’s Watson LIMS;
practice is to involve users in the process early, thereby allowing them to
• Oracle Portal—interactive extranets; and
understand the value of the system and how it can make their work life
• Integrated Clinical’s J-Review.
simpler. For PRA, evaluating client needs during implementation was also critical to ensure key data points were captured. Users need not see
Using the System
CTMS as a technology, but rather as an enabling tool to help support the
CTMS can prove very useful as part of a cross-functional enterprise
customer’s ability to bring drugs to the market sooner, essentially by
system. This might include systems for managing clinical operations,
improving the efficiency of clinical trials.
safety, data management, analysis, and reporting, and even financial data. The technology can significantly improve the value of a company’s
Another important feature of the technology is the ability to calculate
internal systems to facilitate communication and collaboration. The aim
performance metrics and hence make rapid business decisions. If a
of such systems is to allow ease of access to information for staff and
company can monitor how well it performs certain tasks, or how well it
increased visibility of study progress. In this way, different parts of the
carries out an activity in a certain country, it can use those data to
business can communicate—from the investigators, to the clients, to
optimize its workflow, creating a predictive, rather than reactive, system.
the consultants—in a near-realtime fashion.
This of course has huge implications for optimizing decision-making processes, and ultimately benefits the client relationship.
Getting the Information At PRA, using CTMS as the foundation, clients can log into the Oracle
Performance data can be used to help construct proposals and give the
Portal, PRA’s technology for interactive websites, and see information
client a more accurate picture of what is possible within a certain timeline.
about progress of their trial in near-realtime—that is, at a four- to eight-
Being able to set expectations for a deliverable far in advance helps to
hour refresh rate depending on the latency of the data. In the past, this
reduce the uncertainty of questions such as ‘Can we meet enrollment
process would involve running reports, reviewing and aggregating output
based on historical data? In which countries? Using which investigators?’
from other reports, reformatting, and sending to the client via email—a
Consequently, a business development team can go forward with
lengthy and far from ideal situation.
confidence about what it is partnering with the client on, and hence firms can avoid the risk of over-promising and underperforming—or, to put in
Moreover, as the client is able to log in and monitor progress in near-
another way, selling something you cannot deliver.
realtime, there are procedures in place to ensure that the data are clean and that they accurately reflect the current status of a clinical trial. It is
Chasing Clients Not Technology
possible to monitor progress by individual protocol, country, and/or
When praising what CTMS is capable of, it is important not to get carried
investigative site; therefore, access controls limit who has access to
away with technology for technology’s sake. CTMS is only ever useful in
update and alter that information to protect its integrity and validity.
how it can serve the client on a practical level. Clearly, it is important to take pride in the technology your company offers, keeping abreast of
Practical Uses
developments in the field and keeping pace with what other consulting
One area where CTMS can considerably improve workflow is in preparing
firms with the same business model are doing. However, when
project status reviews. Essentially, what used to require up to one week of
considering these technologies it is important to keep the client in mind
staff time can now be completed using an automated process that lasts
by taking feedback and keeping track of actual market need via networks
for around 10 minutes. Using the Siebel eClinical System in conjunction
of professionals and informal community committees. All too often, IT
with a data warehouse, PRA compiles information from a variety of
shops will go out and chase the latest technology without first
sources to construct a high-level status report so that management can
considering what the client really needs and whether the demand exists.
compare data and monitor the progress of a particular clinical trial.
Indeed, CTMS can cause problems and inevitably fail if too much focus is
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placed on acquiring new technologies, rather than what is right for, and
PRA has made changes that actually simplify the system for very-high-
what will fit with, your company.1
volume trials with thousands of investigators and subjects—especially in the areas of managing the recruitment of investigators and managing the
Getting Creative with Clinical Trial Management Systems
thousands of accounts and contacts needed to support the trial.
While CTMS has been an important feature of PRA’s Enterprise Systems for four years, its maximum benefit is gained when utilizing it in a powerful
In combination with the portal, the information delivery system was a
combination of tools. Too often, trying to access the hundreds of variable
focal point with a large client. The technology tools allowed PRA to keep
data points for a large global study to analyze information is difficult at
track of potential subjects to enroll in a trial so that it was easy to identify
best, and transactional reports will not present information in a usable way.
the individuals coming in at different periods and hence notify the client. At the time, this functionality was not available within existing systems.
While CTMS contains critical trial information, it is most powerful when
However, PRA adapted the technology it had to suit those needs, coming
combined with data from other systems and presented in such a way that
up with the idea of web forms and using its portal and portal logs to keep
raw data have been transferred to ‘just in time’ information. PRA has
track of this information, thereby making it possible to contact the client
constructed a custom data warehouse that combines key information
to keep them updated.
from CTMS with information from its other enterprise systems. Key performance indicators and metrics presented together give a 360º view
Enhancements for the Future
of the project for both business and clinical intelligence. When delivered
In the coming months, PRA will be expanding its project status review
to the study team and client through PRA’s interactive web portal, the
reporting capabilities to provide executives with an interactive reporting
barriers to access are removed and true transparency can be established,
solution that presents key financial and operational metrics for each
uniting the client and PRA in a common view to meet a common goal.
executive’s portfolio of projects. Using Siebel Analytics, executives will be presented with a dashboard that aggregates key performance indicators
Some clients opt to skip the investment in their own CTMS and use PRA’s
across client programs. Each dashboard will support drill-down
global platform as the foundation. This enables them to focus on their
functionality so that executives can very quickly ‘dig into’ metrics for
product and place their investment in development, not in technology.
individual projects and/or subject areas of interest to them.
Others, however, choose to deploy a CTMS system and are working with PRA on exports of information so that they have a complete repository of
In the next year, PRA plans on integrating CTMS with its Cisco Enterprise
their trial data. With CTMS and the data warehouse, PRA has been able
Call Center software, providing a unified call center that will allow PRA
to largely automate these exports and quickly transform the data to client
employees to provide a higher level of service to their customers. The unified
systems, making this a repeatable process for any study.
call center will be used to enhance existing services such as study start-up, safety and risk management, product call centers, and PRA’s EDC helpdesk.
Thinking Outside the Box By ‘getting creative,’ CTMS alone and in combination with other tools
Going forward with CTMS, it is important to look at the areas where it
enables the system to push past traditionally viewed limitations. PRA
has succeeded and failed. It can prove difficult to integrate a successful
recently integrated data from CTMS and its electronic trial master file (eTMF)
system without forward planning—this can leave firms having to ‘make
system to solve the problem of case report form (CRF) forecasting and
space’ for CTMS in their infrastructure, which may interfere with ongoing
reconciliation. Understanding when CRFs will be available to be monitored
clinical trials and actually hinder workflow.
and retrieved at an investigative site greatly enhances an organization’s ability to effectively conduct interim monitoring visits, ensuring that study
Clinical Trial Management Systems—
monitors schedule site visits appropriately. In other words, it is not cost-
Past, Present, and Future
effective to monitor too frequently or too infrequently. This, in turn, allows
PRA foresaw that CTMS technology would become increasingly useful as
data management personnel to predict CRF volume and appropriate
clinical trials became more complex and its client base grew, and it is this
resources for high-volume periods so that data entry and review can be kept
forethought that has enabled successful implementation of the
current and backlogs do not threaten study timelines. Integrating data from
technology. Furthermore, the implementation of a standardized
the two systems created the value proposition for the project team members
infrastructure can reduce maintenance costs as a firm grows. Once in
performing the work: it allowed the automatic reconciliation of expected
use, it is important to maximize your CTMS technology by trying to find
CRFs with received CRFs. Previously, this reconciliation was a manual and
new and different ways to use and adapt it for your needs, as
time-intensive process; now it is fully automated, giving study monitors a
demonstrated by the many examples in this article.
valuable reason for keeping CTMS data current and thereby allowing management to make well-informed decisions regarding study monitoring
At present, CTMS appears to be a technology that has now come into its
and data management resources.
own, proving to be an important enabling tool in the management of the large complex trials that have become increasingly common. However, it is
Another way in which firms can extend the reach of this technology is by
not enough simply to install the system—to maximize its value a company
adapting it for use in all trial phases as soon as possible. Currently, most
should be innovative and progressive, looking to exploit all of its systems to
CROs limit their use of CTMS to phases II and III of clinical testing.
support its business. Looking ahead, it seems that this technology will only
However, PRA has been using it across all phases, including phase IV and
become more vital for progress as trials become larger and more complex,
even in some phase I trials. In the case of phase IV and late-phase testing,
spanning more and more populations across the globe. ■
1.
Pratt T, The CTMS Story: Focusing on Need, Applied Clinical Trials, 2006.
ECLINICAL VISIONS
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Clinical Trial Management Systems in the Wild
a report by
Kevin Jarrell Project Leader, Duke Clinical Research Institute
The Duke Clinical Research Institute (DCRI) is the largest clinical academic
CTMS. In parallel, we initiated a project to identify all trials that were
research organization (ARO) in the world. It combines clinical expertise
using the previous programs and, with the aid of a specially designed
and academic excellence with the full-service operational capabilities of a
matrix, determined the ones that were candidates for migration to
major contract research organization (CRO). The DCRI operates with an
CTMS. Some projects were left to simply run out their lifecycle within
approximate 50/50 balance between government-sponsored clinical trials
the old system, while we actively migrated others—at least 10
and industry-sponsored clinical trials, in addition to our academic work,
projects—to CTMS. We are now at a point where we are 100% using
which makes us a niche player in the clinical trial arena.
CTMS, and the previous tools have been retired.
One of the benefits of the CRO-type offering from an institution such as
With the one, holistic product we now have a much higher competency
the DCRI is that we have an academic aspect to our work. We have a real
center, so if end-users have issues they call my team and we are able to
desire to understand the research, understand what the data are saying,
answer their questions. Furthermore, within the clinical operations
and work out how that affects the patient. This attitude can be plainly
organization, because everyone is using the same product you can get
seen in different meetings, in the hallways, and within the DCRI in
immediate help from the person sitting next to you. There are five
general: there is a huge focus on patient care, which is the end goal of
distinct areas where the CTMS has provided benefits to the DCRI.
every clinical trial. Single Source of Information My role is a Line of Business Owner: essentially, I represent the business
The CTMS is our single source of all trial information relating to site
and the business needs. I am the day-to-day decision-maker on what we
management and monitoring, and is useful in helping us get an
do with our clinical trial management system (CTMS) from Siebel (now
understanding of how long it takes for sites to become active and to
part of Oracle). I coordinate with the Director of Clinical Operations.
start enrollment. Once enrollment is under way the system can also help
Together with the Information Technology (IT) Product Manager, I am
us keep track of enrollment trends, how sites have performed, and how
responsible for growing and enhancing the product within the DCRI.
we have performed in reaching enrollment goals.
The Business Value of the Clinical Trial
Such historical information is crucial for successful future trial planning.
Management System
When the DCRI is starting up a new study with specified parameters, it
We have officially been using the CTMS for a little over two years for
is important that my team is able to provide the data that make it
all new projects. Pre-CTMS, we were using two different programs
possible to compare the new study with similar trials that have already
that had been written in-house to capture the same type of
been completed. Timing is the hardest thing to factor in, as it is so
information, both of which were in a production environment, and as
variable among trials. There are large and small trials, long and short
such it was difficult to support and build on the programs.
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
We started out by introducing CTMS in a couple of test projects in a
of all of the data is a very complex job. It has been made easier with the
pilot phase. Once that was deemed successful, we rolled it out across
advent of CTMS because we can query the data, filter them, and then
the organization, and since then all new projects have had to use
receive a report. Previously, we would run a series of separate reports, which were then combined in a spreadsheet for manual analysis.
Kevin Jarrell is a Project Leader for the Duke Clinical Research Institute’s (DCRI’s) clinical trial management system (CTMS). He joined the DCRI in 2007, and since joining the CTMS team he has led several successful major and minor releases/upgrades to CTMS. In addition to managing the day-to-day support team, he is actively planning future development to align with the strategic direction of the DCRI. Mr Jarrell started his career as a Laboratory Technologist in the genetics laboratory of a major central laboratory. He then changed industries and began working at a major clinical research organization as a Clinical Research Associate and Clinical Trainer, before switching departments to become a Senior Information Technology Business Analyst, focusing on improving the company’s CTMS. He received a BSc in biology from Longwood College, Farmville, Virginia.
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
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for another trial we may want 10, and for a third trial we may require 30.
Enhanced Efficiency
Moreover, one trial may need conversation logs while others do not.
The main savings we have realized using CTMS have been in terms of
Similarly, we can specify the number of documents required per trial, and
operational efficiency. The Siebel eClinical product is web-enabled,
so on. Essentially, for each trial we can determine how much or how little
and we have also made it HTTPS-secure so that our monitors can
of each item it needs or the trial team wants to use. Of course,
access it from virtually anywhere. As a general rule, people are much
standardization—for example standard terminology and definitions—
more accustomed to a web interface than to any bespoke program,
sometimes brings its own restrictions. There are always rare examples
and the layout appears logical to them. Using a standard Internet
where one particular group will need something very different from the
browser, users can access the system, enter data, run reports, and
norm, and that is always a challenge. It is a balancing act, trying to meet
obtain information, which was not possible before. The response time
the needs of the 90% without excluding the needs of the 10%.
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.
Regular Upgrades With the CTMS platform, we have been able to structure our software
The major time savings we have seen so far have been around enabling
development lifecycle in such a way that we can put out new
the decision-maker. Having a single place, standard definitions, and
functionality every three to four months. This means that if the end-
standard ways to enter data, allowing all of the different trial team
users identify something they would like to change, we are able to
members to put their data into one place, and then being able to run
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
The major time savings we have
added fields to existing data components or pick lists and segregated
seen so far have been around enabling
data so that only certain users can see them. While this is implicit in
the decision-maker.
the role-based security that the system offers, we have also added extra security. Accounting for Cost
reports on the data, have probably been the areas where we have seen
The labor costs in terms of running and maintaining CTMS are treated
the greatest time savings and the most efficiency. Regardless of the
as an infrastructure expense. Now that we have implemented the
interface, it still takes a clinical research associate the same amount of
product, we are in the maintenance and ongoing enhancement mode.
time to type up a trip report, and there is not a tremendous amount of
This means that for development, as we follow the software
time saved regarding most of the day-to-day routine tasks. Nevertheless,
development lifecycle, we do not have to go back to the Technology
having a tool that users go to every day and become accustomed to and
Steering Committee and request more funds. We are able to dedicate
proficient with in itself generates efficiency: if a task can be completed
staff to the CTMS product and continue to build or enhance it. Using
more quickly, it frees up time to do something else.
this structure, we have been able to build up the product very quickly. 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
It is a balancing act, trying to meet the
has allowed us to integrate and automate some aspects of our
needs of the 90% without excluding
over the next couple of years: trying to ingrain CTMS into our business
the needs of the 10%.
and into our business processes, and in so doing further maximizing
business that are unique to us. This is the aspect that will occupy us
our investment. Having the eClinical product built around our business needs has Targeted User Groups
proved very supportive. We are mindful of what else we could do with
For each new release or upgrade we try to target a primary user group.
the extended functionality, and there are high-level discussions around
While there may be other enhancements that may fit the needs of
where our business could go, but we do not want to be in a position
many other groups, from our perspective the best way to implement
where the software drives the business. Therefore, so far,
an upgrade is to focus mainly on just one user group and deliver
implementing CTMS has not changed our services.
something significant to them. Most of the advantages we have achieved are due to the good At the DCRI there are various user groups, including those that deal with
collaborative working relationship we have at the DCRI between the
site management, site monitoring, safety, and data management;
business and IT sides of the organization. Both sides are in alignment
groups that are responsible for business administration and liaising with
in wanting to do the best we can for the organization, which is not
sponsors; a management team that runs the clinical operations
always the case. Working on a unifying project such as this has helped
organization; a contracts group; and a group that deals with the
cement that relationship, and will hopefully create new ones further
regulatory side.
down the line. ■
ECLINICAL VISIONS
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High Performance—The Place of CTMS
Technology as the Enabler of High Performance— The Place of Clinical Trial Management Systems a report by
Henry Levy Senior Executive, Accenture
In the current climate, the biopharmaceutical industry is experiencing
implemented nearly two decades ago. From these early beginnings, it
unprecedented pressures on multiple fronts. Drug development costs
was expected that clinical trial data collection and management would
continue to spiral upwards, there is increasing generic competition,
rapidly evolve from a paper-based system to an electronic environment,
pipelines are shrinking, and there are pricing pressures from healthcare
with more than 50% of trials being performed using EDC within two to
providers. So, it is no surprise that the industry watchwords in these
three years. The reality is that, due to several factors, progress has been
turbulent times are efficiency, accountability, and control. Based on its
very slow, and it is only in the last two years that Accenture has seen the
experience, Accenture believes that biopharmaceutical companies on the
true adoption of the new model for data acquisition and management.
path to achieving high performance not only need to keep costs contained but also need to ensure accountability of expenditure. Thus, more
Many in the biopharmaceutical industry can now see the value and
companies are embracing technological solutions to help manage their
importance of effective IT and how it can help drive high performance in
portfolio of developmental projects as well as to execute their clinical trials
an organization. However, the need to invest significant capital in
in an efficient and controlled manner. This article discusses some of the
enabling software or technology has been another major barrier to the
major information technology (IT) trends that have affected and will
implementation of effective IT initiatives. To overcome this obstacle there
continue to affect the biopharmaceutical world, and examines the role of
has been a shift away from large single capital investments—often in
clinical trial management systems (CTMS) within this environment.
the range of $20–30 million—toward making IT investment part of the annual expenditure budget. Companies now look to purchase software
Industry Trends
or technology using different financial models that have had a significant
The number of industry-sponsored clinical trials has been steadily rising in
impact on the application landscape. Application service provider models,
recent years. Investigational New Drug submissions at the US Food and Drug
or one-time/per-study/per-site contracting, are examples of these flexible
Administration (FDA) have increased from 542 in 2004 to 662 in 2007—a
approaches to financing clinical trial technology. We have seen how
22% increase.1 Not only are there more trials today, but there is also a trend
these new models allow biopharmaceutical companies to regulate cash
of an increasing number of patients per trial. Trials are also becoming more
flow and, critically, to significantly reduce large capital investments. The
complex and require a higher statistical power to prove safety, specifically in
biopharmaceutical companies are still, in effect, making the same
those areas where new products are targeted to major populations.
investment in terms of overall expenditure, but the new models give
Coupled with the related trend for the biopharmaceutical industry to tackle
companies flexibility in their overall budgeting process and, importantly,
more novel, multifactorial diseases, this all points to trials of greater
are reflected in the figures that are presented to the financial markets.
complexity and longer duration. Furthermore, FDA figures show that the number of new drug approvals has been in general decline since the mid-
Macro Trends
1990s: only 18 innovative new drugs were approved in 2007 (see Figure 1).
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
Micro Trends
decades, the early research phases were perceived purely as a means to
Paradoxically, for an industry that is often at the forefront of scientific
generate innovation and create pipelines. With the considerable decline of
discoveries, the biopharmaceutical sector in general has been a slow
productivity across the pharmaceutical industry, coupled with a near two-
adopter of new IT. Electronic data capture (EDC) technology began to be
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.
Henry Levy is a senior executive with Accenture, based in the US. He is a member of the leadership team for Accenture’s global Life Sciences Research and Development (R&D) practice, where he leads the portfolio of global R&D business and system integration projects. His primary focus for the last 14 years has been clinical development, and his expertise ranges from defining clinical development strategies to implementation of enabling systems, as well as deployment of outsourcing services to support key development processes. Mr Levy speaks regularly at global conferences on a broad range of topics, including new paradigms in clinical development, impact of data integration in the development process, and IT landscape and future trends in R&D. He is a recognized thought leader in these areas. E:
[email protected]
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.
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High Performance—The Place of CTMS
Impact on Research and Development Accenture realizes that the trends discussed previously will have an
Figure 1: Research and Development Spend versus New Drug Approvals
impact on the R&D activities of biopharmaceutical firms. One major effect
50
40
will be rationalization—of pipelines, clinical trials, and patients. At the highest level, this rationalization will result in a reduction in the number
45
35
of trials: companies will have to decide what the focus of their pipeline is
40 30
and make some difficult decisions about which trials to conduct.
optimize ongoing clinical trials. We also anticipate that companies will reduce the number of trials run in
25 No of NMEs
reach a ‘kill’ decision regarding trials more quickly, and can also help
30 25
20
20
15
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
15 10 10
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
5 0
5
2001
2002
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.
R&D spend $bn
35
Adaptive trial design will come to the fore as it will allow companies to
2003 Total NMEs
2004
2005
2006
2007
0
R&D spend (PhRMA members)
Data courtesy of Pharmalicensing. Sources: Burrill & Co, Biotech 2007 Life Sciences: A Global Transformation, PhRMA Annual Membership Survey, 2008; fda.gov NME = new molecular entity.
Outsourcing can potentially achieve a 30–40% reduction in the cost of
customizable, highly configurable CTMS—one that is able to manage
non-core components such as clinical data management, document
different types of environment, from pre-marketing trials to phase IV
management, IT, and application management, and can even reduce
post-marketing studies or country-specific accounts—offers a control
certain costs related to pharmacovigilance and regulatory submissions.
system that can effectively manage disparate resources.
Depending on the company, between 3 and 7% of R&D costs may reflect such non-core elements.
Operational Excellence Operational efficiency—with the ultimate goal of operational excellence—
Crucial Drivers
is essential for proper execution of clinical trials. Achieving operational
For biopharmaceutical companies to meet the objectives of increasing
excellence requires a clear plan and knowledge of both the critical
clinical trial throughput and reducing costs, Accenture sees the need for
milestones and the relevant dependencies. Effective management of a
improvement on several fronts, including control, operational efficiency—
project as complex as a clinical trial requires access to accurate reports that
with a goal of reaching operational excellence—and better decision-
detail the daily status of patient enrollment, updates on how much new
making. Clinical trial management technologies play a central role in
data has been gathered and cleaned, key dependencies on regulatory
providing these capabilities to evolving development organizations.
approvals at the site, and the status of payments to the investigator site. With this information, the heads of clinical development can develop an
Control
understanding of their workload within the context of their whole trial
Go to any biopharmaceutical company today and ask the question: In
portfolio and manage their trial and submissions timelines effectively. With
each therapeutic area, how many trials are you running, and how many
proper resource and project management capabilities, the development
are in phase I, phase II, phase III, or phase IV? Typically, nine out of 10
organization is able to manage its resources effectively and nimbly
companies would take several days to collect and provide that
reallocate resources as projects are cancelled or as priorities change.
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
Decision-making
plans rather than from actual executed plans. This problem is endemic and
Accenture believes that data analytics can add significant value to
can be seen at multiple levels: the number of sites that a company has
improving or optimizing decision-making, while also making the decision-
active at any one time, the number of qualified investigators available to
making process more strategic. Taking advantage of current and
conduct the trials, the number of required certified laboratories—
historical data allows a development manager to be more proactive;
essentially anything related to control over the clinical trial portfolio. These
through modeling and simulation he or she can predict the success of
discrepancies can represent organizational, technological, local, or global
upcoming trials and therefore adjust, in advance, either the design of the
issues. A company may have control over individual pieces of the clinical
trial or the method by which it is executed to reach the optimal level of
trial process, but not consistent and comprehensive control—and without
performance. This predictive capability is achieved by examining the data
that the company lacks the ability to manage its resources effectively.
from, for example, the performance of one investigator over the last five years, combined with knowledge about the relationship between the
The need for control is a principal reason for implementing a CTMS such
clinical trial sponsor and that investigator. In addition, historical site-
as the Siebel Clinical from Oracle. Siebel Clinical’s origins in sales force
performance data across enrollment, quality of data delivered,
automation and customer relationship management provide flexibility in
compliance, and specific patient populations can increase the success
helping companies manage different types of trial. This kind of highly
rates of a site in a clinical trial. As we look forward, we see that coupling
ECLINICAL VISIONS
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High Performance The Place of CTMS of this existing information with new sources such as payer or
10–20% duplicate entries. This inability to distinguish whether the data
prescription data can further improve trial execution.
are clean will hamper new implementations, or at least significantly decrease the value of them. Keeping good data requires intervention.
Within a CTMS, a pre-defined analytics data model coupled with a
This can be achieved by providing appropriate data visibility to multiple
supporting technology platform for mining complex data are now critical
layers of the host organization, including development leaders. Similarly,
parts of the decision-making process for system selections and are key
exposing the data to sites accessible through investigator portals can
differentiators for those vendors that can provide an off-the-shelf
stimulate compliance with data quality initiatives.
analytics capability. Future Perspectives Critical Factors for Achieving High Performance
Accenture
Even after selecting an appropriate CTMS vendor, companies face many
biopharmaceutical firms is how to do more—or at least the same—with
recognizes
that
the
main
challenge
now
facing
pitfalls that can cause delay, increase costs, influence adoption, and,
less, which entails driving productivity and reducing costs. Therefore,
sometimes, lead to failed projects. Critical factors related to avoiding
maximizing the value of data, including clinical and trial management
these pitfalls and achieving high performance include the ability to
data, will be a critical part of development organizations’ objectives. At
manage scope and avoid excessive customization, and avoiding the
the top of the agenda for all R&D leaders who seek high performance is
overintegration of CTMS capabilities with point-to-point interfaces rather
development and enforcement of discipline concerning effective data
than leveraging a service-oriented architecture. However, the most
capture, maintenance, and analysis. This will enable decision-makers to
common reasons for suboptimal implementation of CTMS solutions
more effectively influence clinical trial design and strategic direction while
relate to a lack of balance between system implementation and process
taking a drug through the approval process.
or organizational change during the implementation, and to poor adoption and lack of quality data after roll-out.
Current trial management and data analytics systems can provide companies with effective platforms for achieving better utilization of
Business Integration versus Systems Integration
data. However, companies who seek to be high-performance businesses
Implementing a CTMS is never a solution in and of itself. Appropriate
must also adapt their organizations and their cultures to take full
processes and the right organizational support model must be in place if
advantage of the capabilities available to them, allowing them to be
the technology is to truly enable high performance. In successful
more competitive in the increasingly challenging and complex
implementations the focus is on business integration, not just systems
environment of the pharmaceutical future. ■
integration. Achieving high performance starts with determining business needs and its current processes, identifying the appropriate operating
For more information on how Accenture can help you achieve high
model, and then using technology as an enabler, not as the main solution.
performance, contact Henry Levy at +1 267 216 1827 or
[email protected].
The complexities of data analytics mean that there is more to the process than simply gathering and manipulating vast quantities of data. Many
For more information on Accenture’s High Performance Business research
companies gather and store large amounts of data, yet use only 5–10%
initiative, visit www.accenture.com/global/High_Performance_Business
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
About Accenture’s Health & Life Sciences Group
awareness,’ companies must do more than simply experiment with
Accenture’s Health & Life Sciences professionals deliver innovation and insight to both
techniques and hope for a positive end result. Biopharmaceutical
the private and public sectors of the marketplace, including integrated healthcare
companies must understand good methodology in terms of data
providers, health insurers, managed care organizations, public health organizations,
analytics: to observe what is happening, make a determination, develop
and pharmaceutical, biotechnology, and medical products companies. With more than
theories, and then understand what the actual questions are that must be answered. This type of fundamental scientific thinking is critical before
8,000 professionals dedicated to serving the health and life sciences industry, Accenture is committed to working with clients across the industry to help them achieve and sustain high performance. Accenture works with companies of all sizes,
data analytics can be utilized effectively. By starting with the question to
including 25 of the 27 healthcare and pharmaceuticals companies in the FORTUNE®
be answered before collating the actual data and performing meaningful
Global 500. Its home page is www.accenture.com/h&ls
analytics, companies can create a feedback loop that might allow for the discovery of some of the unknowns in the equation.
About Accenture Accenture is a global management consulting, technology services, and outsourcing company. Combining unparalleled experience, comprehensive capabilities across all
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,
industries and business functions, and extensive research on the world’s most successful companies, Accenture collaborates with clients to help them become highperformance businesses and governments. With more than 186,000 people serving
up-to-date, quality data. This is a particular problem for larger
clients in over 120 countries, the company generated net revenues of $23.39 billion for
biopharmaceutical companies with vast amounts of legacy data. An
the fiscal year ended August 31, 2008. Its home page is www.accenture.com ■
investigator database at any company potentially contains as many as
1. 2.
Parexel, Bio/Pharmaceutical R&D Statistical Sourcebook 2008/2009, Cambridge Healthtech Institute. Press release from Bristol-Myers Squibb, July 24, 2008. Available at: www.investor.bms.com
16
3. 4. 5.
‘Project Impact’ announced in Q4 2007 results on January 31, 2008. Available at: www.wyeth.com/news Global restructuring program announced November 28, 2005. Press release on April 5, 2005. Available at:
6.
www.pfizer.com/news Announced December 13, 2007. Press release available at: www.novartis.com/newsroom/media-releases
ECLINICAL VISIONS
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Clinical Trial Management (Siebel Clinical)
Electronic Data Capture (Oracle Remote Data Capture) Clinical Data Management System (Oracle Clinical)
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Term Classification/Dictionary Management (Oracle Thesaurus Management System)
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Accelerating Insights for Better Health.
Contact Oracle Corporation 500 Oracle Parkway, Redwood Shores, CA 94065
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