ECLINICAL VISIONS

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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

www.oracle.com www.touchbriefings.com

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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.

Published by Touch Briefings Printed by Imprenta Colour Ltd Worldwide distribution by Imprenta Ltd

Where opinion is expressed, it is that of the authors and does not necessarily coincide with the editorial views of Business Briefings Ltd. Statistical and financial data in this publication have been compiled on the basis of factual information and do not constitute any investment advertisement or investment advice. ©2008 All rights reserved

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Contents

ECLINICAL VISIONS CLINICAL TRIAL MANAGEMENT: ENABLING OPERATIONAL EFFICIENCY Introduction New Challenges Call for Innovative Approaches

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Rachel Yang , MD , PhD Director, Product Strategy, Oracle Health Sciences Global Business Unit

eClinical Visions Implementation of a Clinical Management Technology System

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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

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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

12

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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. ■

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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

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eClinical Visions

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Oracle Health Sciences – Clinical Development & Safety Applications

Clinical Trial Management (Siebel Clinical)

Electronic Data Capture (Oracle Remote Data Capture) Clinical Data Management System (Oracle Clinical)

Safety Reporting & Call Center (Oracle Adverse Event Reporting System)

Term Classification/Dictionary Management (Oracle Thesaurus Management System)

Clinical Integration, Warehousing & Reporting (Oracle Life Sciences Data Hub)

Accelerating Insights for Better Health.

Contact Oracle Corporation 500 Oracle Parkway, Redwood Shores, CA 94065

[email protected] www.oracle.com/industries/health_sciences

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