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HEALTH SCIENCES

BRIEFINGS

eClinical Visions

Clinical Trial Management: Enabling Operational Efficiency

Contents:
New Challenges Call for Innovative Approaches Rachel Yang, Oracle HealthSciences

Technology as the Enabler of High Performance—The Place of Clinical Trial Management Systems Henry Levy, Accenture

Implementation of a Clinical Trial Management System Jennifer Hunt, Genzyme

Clinical Trials Management of the Future Jeannie Inge and Jason Packwood, PRA International

Clinical Trial Management Systems in the Wild Kevin Jarrell, Duke Clinical Research Institute

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ECLINICAL VISIONS
CLINICAL TRIAL MANAGEMENT:
ENABLING OPERATIONAL EFFICIENCY
Editorial
Managing Editor Michelle Grayson Technical Editors Dr Patrick Wong Claire Thomas Sub-editorial Manager Claire Dunn

BRIEFINGS

Operations
Associate Director—Operations Tim Green Designer Christian Fanslau

Business Development
Associate Director—Bespoke Publications David Ramsey

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Michelle Grayson T: +44 (0) 20 7452 5181 F: +44 (0) 20 7452 5050 E: michelle.grayson@touchbriefings.com

In association with:

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Tim Green T: +44 (0) 20 7452 5023 F: +44 (0) 20 7452 5610 E: tim.green@touchbriefings.com

HEALTH SCIENCES

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Contents

ECLINICAL VISIONS
CLINICAL TRIAL MANAGEMENT:
ENABLING OPERATIONAL EFFICIENCY
Introduction
New Challenges Call for Innovative Approaches
Rachel Yang , MD , PhD
Director, Product Strategy, Oracle Health Sciences Global Business Unit

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eClinical Visions
Implementation of a Clinical Management Technology System
Jennifer Hunt
Senior Director, Clinical Research, Genzyme Corp.

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Clinical Trials Management of the Future
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

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Clinical Trial Management Systems in the Wild
Kevin Jarrell
Project Leader, Duke Clinical Research Institute

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Technology as the Enabler of High Performance— The Place of Clinical Trial Management Systems
Henry Levy
Senior Executive, Accenture

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© TOUCH BRIEFINGS 2008

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 undergoing a remarkable transformation. Coupled with this muchneeded evolution are new challenges specific to the increasing role that information technology will play to enable the new clinical development landscape. Of the many challenges facing the biopharmaceutical industry today, the critical need for greater operational efficiency in clinical drug development is paramount. With flat and even declining productivity, rising research and development (R&D) costs, more complex preapproval trials and large post-approval studies driven by the shift toward biological agents, and increasing regulatory demands, it is essential that clinical trials are managed more effectively and efficiently. While progress has been made in addressing these challenges, companies are increasingly turning to clinical trial management systems (CTMS) to improve trial efficiencies, cut trial costs, and enhance the productivity of trial participants. The Globalization of Clinical Trials The global clinical trial, while not new to either sponsors or clinical research organizations (CROs), is becoming more prevalent. Clinical trials are increasing in size and complexity and more global trials are being conducted with sites across diverse geographical regions. The predicted trend is that there will be a significant shift from North America/Western Europe to the Asia-Pacific region (APAC). Between 2008 and 2010 the percentage of trials conducted in North America/Western Europe is expected to fall from 55 to 38% (see Figure 1).1 Clinical trials conducted in APAC countries offer potential cost savings as well as large patient populations, particularly of treatment-naïve patients. This shift will also have certain implications. Sponsors and CROs will need to support all operational aspects of global trials: languages, logistics, access control, regional requirements, and region-specific business processes. Furthermore, it will be necessary to understand and meet local regulatory requirements. To manage global trials more efficiently, many companies turn to commercial CTMS. These CTMS are typically implemented as enterprise applications. A fundamental value proposition of an enterprise CTMS is the provision of a centralized trial repository, which enables standard trial management processes across the enterprise and provides end-users, who increasingly are more geographically diverse, with realtime data visibility into study progress. However, this does not necessarily mean that everybody who is involved in a study should have access to all information about it. Organizations should balance the need to empower their employees with access to available information against keeping tight control over data access, allowing only those with proper authorization into the appropriate files. Fortunately, technology solutions exist that provide

the access control necessary for the clinical trial industry, as well as tools that significantly reduce the administrative overhead. The globalization of clinical trials needs to be truly worldwide rather than just a process of more trials conducted in different locations. This will require global unified systems with built-in functionality that supports specific regional needs. The current mindset, however, is still more or less focused toward the traditional North America/Western Europe requirements and supporting prevailing business needs. For a truly global system, this view needs to change to ensure individuals and departments have an understanding of where they fit into the business process. Regional units need to understand how their work affects others in the process so that effective collaboration can take place. It is also important to assess the impact or implication that local infrastructure and culture might have on conducting clinical trials in developing countries. Understanding the local environment and requirements often drives innovation that brings about substantial impact. Innovative solutions that are very site-focused, very pragmatic, and very specific to the local infrastructure may overcome barriers. For example, patient follow-up is a significant issue in China. A large Chinese CRO has proposed utilizing mobile technology, in the form of cell phones, as a component of its site management system. The proposed system would allow stakeholders to send the alerts or messages via SMS, or push reminders to patients regarding visits. This form of collaborative tool, along with better data visibility, will help clinical research associates (CRAs) better manage their sites and increase study compliance. Increased Outsourcing of Clinical Trials It is estimated that 20% of the biopharmaceutical industry’s R&D spend is on outsourcing. Coupled with the increasing globalization of

Rachel Yang, MD, PhD, is Director of Product Strategy 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: rachel.yang@oracle.com

© TOUCH BRIEFINGS 2008

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Introduction
allow both pre-marketing and post-marketing safety data to be viewed holistically and longitudinally will become increasingly necessary.
Eastern Europe 10% 13% 3% 5% 3% India 5% 4% China 7% 2006 2010

Figure 1: Geographical Distribution of Clinical Trials

eClinical Adoption Drives Systems Integration and Support of Cross-application Business Processes Electronic data capture (EDC) is taking hold and significant progress has been made in the last decade in terms of leveraging EDC and other eclinical technologies in conducting clinical trials. Consequently, subject enrollment information no longer comes in the form of faxed enrollment logs. Rather, it often comes from interactive voice response systems (IVRS) or EDC. This means that CRAs can obtain strategic information about a trial’s progress and case report form (CRF) information during a trial without having to travel to the site. Therefore, CTMS is no longer the system of entry for many such data, yet

Rest of Asia

Middle East and Africa

7% 14%

to get a clear picture of study conduct, view actual patient enrollment against plan, track actual payments against budget, and forecast workload and resources needs, it is imperative for CTMS to have accurate data on information such as patient enrollment as well as CRF completion. Manually entering data into CTMS after they have been
25% 19% 30% 19%

Central and South America

15% 11%

Western Europe

entered into other systems is highly undesirable since it is labor-intensive and error-prone and requires costly conflict resolutions. Thus, integration with other systems becomes necessary.

North America

Vendors who have built products/applications on standard-based open architecture offer compelling value in assisting biopharmaceutical
25% 30% 35%

0%

5%

10%

15%
1

20%

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 down the traditional barriers between systems by providing a common platform on which to build solutions that can be shared as interoperable services. Oracle is leading the effort to develop next-generation SOAbased applications for the clinical industry. These will provide better support for business processes that span multiple applications, and will reduce the need for costly point-to-point integration. Declining Number of Investigators and a Limited Number of Trial Sites Tufts reports a continuing decline in the number of US investigators. Moreover, there has been an increased use of first-time investigators, with 50% of investigators never conducting a second trial. This issue of poor investigator retention, especially in the US, is a major challenge. Investigator recruitment and retention remains one of the most important aspects of clinical trials. Poor retention rates suggest that there is a need to innovate the approaches currently used to identify and target suitable investigators, and to retain good investigators. Biopharmaceutical companies need to build stronger, more personalized relationships with investigators to foster loyalty. Investigator loyalty gives biopharmaceutical companies a strong competitive advantage. There are several strategies that biopharmaceutical companies can use to strengthen the relationships with their investigators: by providing the necessary information at their fingertips with easy-to-use productivity tools that make conducting clinical trials less time- and resourceconsuming, by paying investigators quickly and accurately, etc. Fortunately, leading CTMS vendors have adopted a customerrelationship management paradigm and methodology and developed robust features to allow companies do just that. By assisting

Adapted from McDonnell & Mooraj, AMR Research.

clinical trials, the cumulative result is a need for greater sharing of information between all stakeholders. Among CROs, sponsors, central laboratories, and other participating service providers, the need for increased data sharing is inevitable. CTMS that are built on open architecture and facilitate data exchange with third-party applications bring significant cost savings to biopharmaceutical companies and CROs. Increased outsourcing also means that biopharmceutical companies will likely work more with different CROs in the future, and vice versa. Thus, having a flexible CTMS that can be easily modified as business needs change offers long-term benefits to biopharmaceutical companies and CROs. Growing Demand for Post-marketing Studies Another recent trend is the growing demand from regulatory agencies in the US, Europe, and Japan for large-scale post-marketing studies as a condition for approval. Indeed, according to Tufts, between 1998 and 2008 75% of new drugs approved in the US and the EU, and 50% of those approved in Japan, had post-marketing study commitments attached to the approvals.2 Post-marketing studies are typically much larger in scale, with hundreds or even thousands of sites and many more patients. Managing large-scale trials carries unique challenges. While pre-marketing studies focus on data quality for each individual patient, post-marketing studies place greater emphasis on sampling and automation. CTMS that have built-in workflows that can be easily set up and modified are well suited to the rigors of post-marketing studies. The greater focus on safety monitoring and pharmacovigilance also means that CTMS that support both pre- and post-approval clinical trials offer distinct advantages. Integration with safety surveillance systems that

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ECLINICAL VISIONS

New Challenges Call for Innovative Approaches

investigators and providing them with the best possible trial experience, individual companies will set them apart from their peers and see improvement on investigator retention. As more companies conduct EDC trials, investigators are required to enter data directly into each company’s EDC systems. For those who are performing multiple EDC trials, this often means having to log on to multiple different systems, or even carry several laptops. There are also CTMS portals that provide useful trial information as well as differentiated services to investigators. While each of these applications has a unique 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 clinical trial needs of investigator sites. This is also why it is so important for the technology industry to work closely with regulatory agencies and standards bodies such as the Clinical Data Interchange Standards Consortium (CDISC), SAFE, and the Clinical Research Information Exchange (CRIX). A greater culture of collaboration, with crossgovernment and cross-industry initiatives that look at the business process in terms of addressing needs rather than from the traditional multiple platforms from multiple vendors aspect, will help to streamline the process and create greater efficiency. Adaptive Trials—A Reality of Clinical Trial Evolution Adaptive trials will become a reality or even a necessity rather than just a concept. Regulatory agencies in the major markets have implemented evolving positions on adaptive clinical trial design, and information technology (IT) vendors are developing software to support adaptive designs. Adaptive design uses accumulating data to decide how to modify aspects of the study so that the right development questions can be answered more efficiently and accurately without undermining the validity and integrity of the trial. Adaptive design also provides patients participating in a trial with a greater probability of being allocated to treatment that works than in a traditionally designed trial. Much of the focus has been on statistical design of adaptive trials and impact on patient data capture, while very little has been done in terms of supporting adaptive trials from the trial management and operational perspectives. Traditionally, a study is set up when just about every step has been properly mapped out in a study protocol. Adaptive trials challenge the traditional model and call for greater flexibility on study set-up, site set-up, study design, and patient enrollment. Unfortunately, many current CTMS are built for the traditional clinical design, and only a very few CTMS vendors have started building functionalities that provide the flexibility for adaptive trial designs. One adaptive element that is not talked about in the context of adaptive trials is the ability to ‘adapt’ and modify how trials should be ‘executed’ rather than ‘designed’ based on realtime information available on the study progress. Embedding analytics solutions in clinical applications transforms applications such as CTMS and clinical data management systems (CDMS) from being places where data are simply entered and stored to places where business intelligence is gained and actionable insights are generated by and for the end-users. Embedded business intelligence will not only enhance the value of clinical systems, but also help drive end-user adoption.

The Reality Now and Looking to the Future Increasing globalization of clinical trials, driven by the need to lower costs and recruit participants; greater outsourcing; more complex trials and postmarketing studies. These are just some of challenges facing the biopharmaceutical industry. Many of these issues can be addressed to some degree with currently available IT technology. However, as the technology evolves, it will sustain and drive forward the eclinical vision. Collaboration tools that make all participants in clinical trials more productive can only be beneficial, and robust CTMS solutions that are built to support business processes instead of focusing on collecting data will come to the fore. For this publication, we have received contributions from experts within and supportive of the biopharmaceutical industry. These experts talk about their overall views of the future of clinical trials and the process of implementing a CTMS that not only helps their day-to-day job but also brings efficiency to their organizations. Jennifer Hunt, Genzyme, describes the thought processes engaged and the procedures followed when Genzyme set out to search for a CTMS. The dual aims of the quest were to contain trial costs and provide insight into study progress across the entire organization. The resultant CTMS system, while still very much a work in progress, is slowly becoming the authoritative source for clinical trial information at Genzyme. Kevin Jarrell, Duke Clinical Research Institute (DCRI), shares with us the business benefits of implementing a CTMS. It has been customized to suit the particular needs of DCRI as an academic research organization, and has empowered the decision-makers and encouraged collaborative working across the whole organization. Jeannie Inge and Jason Packwood, PRA International, illustrate how a forward-looking company can embark on a technology expedition and use IT creatively to improve operational efficiency, optimize decisionmaking, and contain costs. PRA’s CTMS has allowed the CRO to steadily grow its client base, its geographical footprint, and the size and complexity of the clinical trials it runs. Henry Levy, Accenture, describes technology as an enabler of high performance. He outlines Accenture’s view of macro and micro trends in the biopharmaceutical industry and how these will help drive faster technology adoption. For companies that seek to employ technologies in general—and CTMS in particular—it is not enough to simply ‘plug and play’; firms must adapt their organization to take full advantage of the technologies and improve their business. We are grateful to our authors and contributors for their insights, and trust you will find their experiences and views relevant and enlightening. Looking ahead, Oracle sees great opportunities to help the biopharmaceutical industry re-energize drug development by providing innovative technologies. Oracle’s vision is to provide a set of integrated clinical trial solutions that is SOA-based and built on standard middleware technology with integrated business intelligence, and can be offered as ‘software as service.’ We look forward to your thoughts and feedback. ■

1.

McDonnell W, Mooraj H, Clinical Trials Are Moving Out, May 13, 2008. Available at: www.amrresearch.com

2.

Postmarketing studies are becoming the norm in U.S., Europe, and Japan, Tufts CSDD Impact Report, 2008;10(4).

ECLINICAL VISIONS

5

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 management system (CTMS). It acts as a central repository for all best practices and company-specific information, as well as providing a way to control and streamline clinical operations. This article will explore the process of selecting, deploying, and maintaining a CTMS within an international biopharmaceutical firm, highlighting issues and unexpected benefits that have been encountered along the way. Genzyme is a biopharmaceutical company that has grown from a small Boston-based start-up in 1981 into a global diversified enterprise employing more than 10,000 people. Having started as a specialist in ultra-orphan indications of rare genetic diseases, Genzyme now has several different clinical groups, focusing on lysosomal storage disorders, oncology, orthopaedics/biosurgery, transplant/immune diseases, and renal, as well as a genetics/diagnostics group. As a way to help facilitate the conduct of its clinical trials and provide support for the tools and resources across all of the therapeutic areas for the company globally, in early 2008 Genzyme established a Global Clinical Operations department.

Contemplating Clinical Trial Management Systems Genzyme initially had a system that had been built in-house by the Data Management group, which fulfilled that group’s needs very well: it could track case report forms (CRFs) and data clarification forms and manage workload. However, attempts to build in functionality, such as that found in a CTMS, to help the Clinical Research department were not successful. As a result, people within Clinical Research did not use it. Thus, primarily through the use of spreadsheets, each team developed its own solution. The current CTMS effort began in 2004, with basic discussions around containing costs and getting more insight into study progress across all of the therapeutic areas. There was a need to create efficiencies by looking at best practices, centralizing all information about the studies, and providing a tool for clinical users to help manage their daily operational activities. It was a long process, and everyone involved from Genzyme was fully allocated to project work in addition to being part of this initiative. However, there was a common passion directed toward realizing operational improvements. 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 project management, particularly for the ultra-orphan indications that require highly specialized knowledge. For most indications, the company also employs external monitors (clinical research associates [CRAs]) to provide flexibility in recruiting monitors across the geographies. Whether internal or external, CRAs travel to study locations and ensure that the investigators and institutions are adhering to good clinical practices (GCPs) and following the clinical study protocol, as well as checking that the subjects recruited meet the criteria for the study and making sure that all of the regulatory documents are in order. The study data are brought in-house and processed by Genzyme’s Data Management group.

selecting a system, the next step was to define Genzyme’s requirements and needs from a CTMS. It was also important to examine the most crucial standard operating procedures (SOPs), breaking them down into process maps to see where a CTMS could be utilized to automate the process. Only once this had been done was it worth looking at the different CTMS options available and matching them up with Genzyme’s needs. All of the top choices came in and presented. Although the different systems had superficially very similar functionality, significant differences existed. The Siebel CTMS from Oracle has a sales history and therefore has a built-in concept of what it takes to make a study site: the doctor, who is the ‘contact’; a hospital as an ‘account’; and then the study protocol on top. The Siebel system also had an inherent flexibility to permit customization to conform to Genzyme’s particular processes. In addition, it had the best feedback and very good references of the choices presented. Overall, selection of a system was a long and challenging process. It involved comparing Genzyme’s requirements against each of the system’s capabilities. However, while requirements and capabilities may align on paper, until a system is deployed and utilized both the strength of the requirements and the depth of the capabilities cannot be fully tested. Deployment Timescale The initial deployment occurred in February 2007, and by the end of 2008 Genzyme will have completed the second phase of development, which includes many updates and enhancements. This process has differed from

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.

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© TOUCH BRIEFINGS 2008

Implementation of a CTMS

Figure 1: New Clinical Trial Management System Users Created
90 80

70 60 Number of users

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 that, while the initial design was not perfect, sufficient useful functionality would drive end-user utilization, which in turn would create the helpful feedback for additional releases. This has proved to be the case, with an increasing number of users adopting the system (see Figure 1).

studies. If someone is initiating a new program, he or she can contact Global Clinical Operations and get help in laying the foundation, including finding the resources, entering the protocols into the CTMS, retrieving the information, and any other technology needs. Within Global Clinical Operations is the Clinical Process and Technology

One of the trade-offs is that the more customized a system is to meet specific needs, the more of a challenge it can be to upgrade to the next standard. While Siebel CTMS is highly configurable with the Siebel Tools and provides full upgrade paths for configurations, excessive customization is highly discouraged as it can make upgrades challenging. Judicious use of the Siebel Tools to configure the application is the key, and in fact Genzyme has been able to keep configuration to less than 15%. Organizational Linkages Bringing in a CTMS creates waves. It is not an enclosed system: there are many opportunities for integration with other systems and opportunities to share data. Sometimes that will include taking a step back and determining the authoritative source: identifying the sole place within Genzyme where a data element is first entered, regardless of system, and then sharing it. Doing this makes it possible to avoid redundancy and duplicative entry, which can lead to errors. Similarly, along with unifying the data system, by creating the Global Clinical Operations group the hope is that the task of running this system can be centralized. This will allow others in Clinical Research more time to focus on conducting clinical trials. Global Clinical Operations can assume responsibility for not only executing CTMS but also looking to create synergies elsewhere as the company as a whole moves toward an even more global outlook: expanding into China and India, for example. It is important to be able to create consistency, even while running studies in several geographies across different therapeutic areas in each of the business units. This group will help move resources quickly and provide senior management with a common understanding and insight into the progress of the clinical development programs. It is also intended to be a resource for all new

group, which manages the CTMS, including evaluating the use of electronic trial master files, dealing with reporting issues, planning for studies, and helping people use the technology to make their jobs easier. There are also groups that focus on resourcing, contracts and vendors, study feasibility and subject recruitment, pharmacy-related issues, and, lastly, handling SOPs, best practices, and training. Learning the New System Having now implemented CTMS at Genzyme, there is an opportunity to reflect on the other in-house systems in order to identify clinical processes that do not currently have an effective tool and see whether the CTMS can help solve them. It has also been very helpful for Genzyme to become active with the extended Oracle user community. The system is very flexible and different companies are using it in a variety of ways. Communicating with other organizational users of Siebel CTMS is a valuable strategy: it has allowed us to share our company’s experiences and best practices with other firms, and vice versa. For example, one of these organizations is a pharmaceutical company that is much larger than Genzyme, and there have been periods of collaboration over the past two years that involve sharing non-confidential ideas about training and system enhancements, often resulting in suggestions for improvements that are then passed on to Oracle. Overall, adoption at Genzyme has been very good. People have been very pleased with the functionality. The CRAs, for example, have to create a report after a site visit; previously this was written using a Microsoft Word template, but with the CTMS all of the templates and all of the questions are now in the system, making the process of reporting simpler and quicker. One of the main intentions of the system is to try to stop people from creating their own spreadsheets to track details about any given study. A survey was conducted at Genzyme’s European headquarters in

ECLINICAL VISIONS

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Implementation of a CTMS
Amsterdam that calculated how many spreadsheets people used before the implementation of CTMS compared with afterwards. Between April and December 2007, there was a 20–40% decrease in the number of spreadsheets used, but not total elimination. However, instead of banishing the spreadsheets, following the implementation of phase one the users in Clinical Research were asked what they were still tracking in spreadsheets, and as a consequence several pieces of functionality are being added in phase two. Issues and Teething Problems The process of deployment and assessment has not only uncovered additional functionality to be added, but has also highlighted unnecessary functionality that can be removed. This includes some requirements determined prior to system selection. One example is the ability to work and write reports within CTMS while users are offline. The Authoritative Source A major revelation connected with CTMS is how much this system affects those outside of Clinical Research and the need to engage these groups. For example, metrics that help benchmark the efficiency of Genzyme’s clinical trials rely heavily on data contained within CTMS. Thus, there needs to be a reporting tool to allow data retrieval, but it is also vital to ensure that the data are accurate and that there is a high level of compliance. In addition, terminology needs to be standardized so that protocols We have seen benefits and cost savings since we started to use CTMS; however, quantifying the cost savings remains a challenge. Costs can be decreased in several ways: a task that used to take four hours to complete may take only two hours with CTMS; therefore, people can do more tasks. Alternatively, the actual external dollars now spent can be compared with former spend: for example, a CRA’s trip report would have previously been sent—signed with a wet signature—by Federal Express; with CTMS, the approval process is completed electronically. The actual costs have not yet been calculated, although an administrative survey was carried out prior to the initial roll-out. This survey addressed the time taken for common tasks; a re-administration of the survey will be able to assess any change.

By making CTMS the authoritative source, people will not have to reinvent the wheel each time to deal 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 the country and could not always connect to the Internet to access the system. This capability enabled CRAs to have full access to CTMS functionality without being connected to the Internet. The idea was that CRAs would synchronize at least daily to upload all of their offline reports into the system and download any changes from the system. While the remote capability did help CRAs be more productive while on the road, it also brought some unanticipated challenges. For instance, if a contractor suddenly leaves the company with information stored in his or her computer, this weakens the system and raises a potential issue of confidentiality. If synchronization is not completed frequently, data integrity and speed can be affected. After weighing the pros and cons of enabling remote capability, Genzyme has now made a decision to disable the remote capability. Currently, Genzyme issues wireless cards to certain staff who travel frequently so they can log on through a mobile telephone system, connecting through a private virtual network. In this way users are always securely connected to the live system and no data are stored on laptops.

consistent, technology-independent nomenclature overseen by one Genzyme-wide group. A word proposed for a new protocol status can be posted centrally and assessed by all users. For example, the word ‘active’ when applied to a trial seemed ambiguous, and was changed to a status of ‘enrollment open.’ Once a decision such as this is made, the system is then manually cleaned up and made consistent. Applying the highest standards possible to the CTMS has encouraged other groups to ask whether they can pull data from the system because it has become the authoritative source—the first place that any piece of data will be entered. People from the business units use it to generate high-level reports about all of Genzyme’s programs. Furthermore, given the US Food and Drug Administration’s requirements for posting of clinical trials and results, this type of information can also be drawn from the CTMS by Regulatory Affairs Compliance groups. Such groups will have additional data requirements that can in turn be added to the system where appropriate. By making CTMS the authoritative source, people will not have to

The ability to produce reports from the data contained within the system has also taken time to develop. It would have been a very timeconsuming process to analyze and derive a top 10 list of reports in the development phase. Therefore, an alternative is to allow ad hoc reporting, which will be released shortly. This will be monitored and the data collected so that it is possible to determine which reports work and which ones do not, and which ones are very popular and which ones less so. From the ad hoc reporting tool, a list of 20 or more reports can be compiled and made available to all users in the system, removing the need to use ad hoc reporting and creating uniformity and speed.

reinvent the wheel each time to deal with a specific problem. The CTMS can drive best practices and help establish a common agenda for a set of reports, allowing clinical professionals to focus on running studies and, ultimately, getting products approved. The process of determining which system to install and how to use and maintain the system is a significant undertaking. Ultimately, successful adoption should improve and streamline all functions within Genzyme and help unite the different departments. A big part of the learning process with CTMS is that simply installing a system is not sufficient to allow declaration of success. There is much more work to be done to ensure that a CTMS is useful, and to achieve and maintain these goals. ■

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Clinical Trials Management of the Future

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 pressure on a company’s ability to conduct them efficiently. This has led to the need for clinical development firms to implement new technologies such as clinical trial management systems (CTMS) to improve workflow efficiency. Furthermore, firms can maximize the potential of systems such as these by using them in innovative ways to cut the time and costs required to take a drug through development. Clinical research organization (CRO) PRA International has

However, times are changing. Developments in Oracle’s systems have enabled CTMS to be offered at a lower cost than before, allowing more companies access to the technology. Now, many companies are reliant on CTMS technology to manage numerous trials. With this reliance has come the demand for information and ease of access to this information so that individuals can make rapid business decisions. This demand is what has necessitated pushing CTMS tools to a new level of performance, use, and scalability. In addition, the notion of transparency between the client and CRO is paramount. PRA’s experience using CTMS has been positive, and the key to that success has been thinking ahead: the firm had been anticipating the market and preparing its systems so that it could ‘slot’ a CTMS into the established business model. The company envisioned a 10-year plan (beginning in 1998) to create a standardized, robust, and scalable information technology (IT) infrastructure that is able to adapt as the business grows, taking on more and more complex trials. It has also proved important to develop a standardized network infrastructure, where all employees across the world have the same hardware and software, to avoid complications with maintenance as the company expands. At the fundamental level of the technology plan are the enterprise systems themselves, which comprise various applications (see page 10). All the data

implemented some 20 enterprise systems in the last eight years. This article will discuss PRA’s experience with these systems, primarily CTMS, and how they have increased efficiency and reduced costs. It also describes how PRA has leveraged its current technology to meet new needs and how this bodes for the firm’s future. The article will also look at ways to use CTMS to cope with changing trends and keep pace with future developments in the field. The Changing Face of Clinical Trials Over the last 10 years, PRA has seen its client base grow dramatically. It has gone from a company managing trials confined to one country, for example in the US, Canada, or Germany only, to one that runs huge projects spanning the globe, in some cases with sites in more than 30 countries. As PRA has grown, the firm has had to adapt its technology to deal with a changing customer base and more complex clinical trials. When conducting multicenter trials based in 30 countries or more, the communication overheads can be staggering. Creating enterprise tools and developing solutions that can help to reduce that overhead and help teams communicate more effectively is one of the major challenges that clinical development firms face today. As well as facilitating communication, a CTMS can also be used to automate processes and cut administrative tasks to a minimum. The technology addresses organizational issues, allowing a firm to manage its resources with consistent control over all departments within the company. An effective CTMS can reduce communication overheads, support protocol feasibility, facilitate the management of investigative sites, cut down on administration, and save money in the process—something of extreme importance in the current economic climate. Clinical Trial Management Systems—A Brief History In the early days of CTMS, the pharmaceutical industry was quite conservative in its use of the technology owing to concerns over the security of data and the safety of intellectual property. A CTMS was also very costly to implement, with companies having to invest in large amounts of hardware and training, not to mention the license cost.
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). 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.

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Clinical Trials Management of the Future
from here are stored in a data warehouse that can assemble the required information as necessary, allowing it to be viewed via the delivery portal. The nuts and bolts of this infrastructure include a standardized IT solution on Dell Hardware, Microsoft platforms, and, largely, Oracle databases. The infrastructure is based on Cisco Networks, with AT&T being the global provider. As noted previously, the company boasts the success of 20 individual enterprise systems since 2000, all of which met project deadlines and budgets. Among these notable industry leaders include: • Electronic Trial Master File System—a proprietary document management system based on Documentum; • Lawson ERP; • Siebel e-Clinical and Customer Relationship Management; • Oracle Adverse Events Reporting System with E2B compliance; • ClinPhone EDC; • Siebel Analytics (OBIEE) for Data Warehousing; • Oracle Clinical and RDC; • Insight Publisher with eCTD Compliance; • Cisco Enterprise Call Center; • Thermo Fisher’s Watson LIMS; • Oracle Portal—interactive extranets; and • Integrated Clinical’s J-Review. Using the System CTMS can prove very useful as part of a cross-functional enterprise system. This might include systems for managing clinical operations, safety, data management, analysis, and reporting, and even financial data. The technology can significantly improve the value of a company’s internal systems to facilitate communication and collaboration. The aim of such systems is to allow ease of access to information for staff and increased visibility of study progress. In this way, different parts of the business can communicate—from the investigators, to the clients, to the consultants—in a near-realtime fashion. Getting the Information At PRA, using CTMS as the foundation, clients can log into the Oracle Portal, PRA’s technology for interactive websites, and see information about progress of their trial in near-realtime—that is, at a four- to eighthour refresh rate depending on the latency of the data. In the past, this process would involve running reports, reviewing and aggregating output from other reports, reformatting, and sending to the client via email—a lengthy and far from ideal situation. Moreover, as the client is able to log in and monitor progress in nearrealtime, 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 possible to monitor progress by individual protocol, country, and/or investigative site; therefore, access controls limit who has access to update and alter that information to protect its integrity and validity. Practical Uses One area where CTMS can considerably improve workflow is in preparing project status reviews. Essentially, what used to require up to one week of staff time can now be completed using an automated process that lasts for around 10 minutes. Using the Siebel eClinical System in conjunction with a data warehouse, PRA compiles information from a variety of sources to construct a high-level status report so that management can compare data and monitor the progress of a particular clinical trial. Chasing Clients Not Technology When praising what CTMS is capable of, it is important not to get carried away with technology for technology’s sake. CTMS is only ever useful in 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 developments in the field and keeping pace with what other consulting firms with the same business model are doing. However, when considering these technologies it is important to keep the client in mind by taking feedback and keeping track of actual market need via networks of professionals and informal community committees. All too often, IT shops will go out and chase the latest technology without first considering what the client really needs and whether the demand exists. Indeed, CTMS can cause problems and inevitably fail if too much focus is Performance data can be used to help construct proposals and give the client a more accurate picture of what is possible within a certain timeline. Being able to set expectations for a deliverable far in advance helps to reduce the uncertainty of questions such as ‘Can we meet enrollment based on historical data? In which countries? Using which investigators?’ Consequently, a business development team can go forward with 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 another way, selling something you cannot deliver. Another important feature of the technology is the ability to calculate performance metrics and hence make rapid business decisions. If a company can monitor how well it performs certain tasks, or how well it carries out an activity in a certain country, it can use those data to optimize its workflow, creating a predictive, rather than reactive, system. This of course has huge implications for optimizing decision-making processes, and ultimately benefits the client relationship. Clinical Trial Management Systems for the Client Despite all of the benefits of using CTMS, there can still be issues with user acceptance—the ‘what’s in it for me?’ problem. Does the system provide the data that both the client and the PRA team need? The best practice is to involve users in the process early, thereby allowing them to understand the value of the system and how it can make their work life simpler. For PRA, evaluating client needs during implementation was also critical to ensure key data points were captured. Users need not see CTMS as a technology, but rather as an enabling tool to help support the customer’s ability to bring drugs to the market sooner, essentially by improving the efficiency of clinical trials. 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 leveraging its existing enterprise systems. Data warehousing technology is used to extract all of the data needed from systems such as Lawson Financials, CTMS, and Oracle Clinical. These data are transformed into useable information compiled into a single report and delivered by PRA’s portal. Prior to 2007, PRA compiled reports for monthly project status reviews by collecting data from different systems and populating very complicated Excel spreadsheets. As well as encroaching on staff time—reports can require around 600–700 different data points from many different functional areas—the company estimated that it was costing more than $1 million to prepare these project metrics each year.

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Clinical Trials Management of the Future

placed on acquiring new technologies, rather than what is right for, and what will fit with, your company.1 Getting Creative with Clinical Trial Management Systems 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 combination of tools. Too often, trying to access the hundreds of variable data points for a large global study to analyze information is difficult at best, and transactional reports will not present information in a usable way. While CTMS contains critical trial information, it is most powerful when combined with data from other systems and presented in such a way that raw data have been transferred to ‘just in time’ information. PRA has constructed a custom data warehouse that combines key information from CTMS with information from its other enterprise systems. Key performance indicators and metrics presented together give a 360º view of the project for both business and clinical intelligence. When delivered to the study team and client through PRA’s interactive web portal, the barriers to access are removed and true transparency can be established, uniting the client and PRA in a common view to meet a common goal. Some clients opt to skip the investment in their own CTMS and use PRA’s global platform as the foundation. This enables them to focus on their product and place their investment in development, not in technology. 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 their trial data. With CTMS and the data warehouse, PRA has been able to largely automate these exports and quickly transform the data to client systems, making this a repeatable process for any study. Thinking Outside the Box By ‘getting creative,’ CTMS alone and in combination with other tools enables the system to push past traditionally viewed limitations. PRA recently integrated data from CTMS and its electronic trial master file (eTMF) system to solve the problem of case report form (CRF) forecasting and reconciliation. Understanding when CRFs will be available to be monitored and retrieved at an investigative site greatly enhances an organization’s ability to effectively conduct interim monitoring visits, ensuring that study monitors schedule site visits appropriately. In other words, it is not costeffective to monitor too frequently or too infrequently. This, in turn, allows data management personnel to predict CRF volume and appropriate resources for high-volume periods so that data entry and review can be kept current and backlogs do not threaten study timelines. Integrating data from the two systems created the value proposition for the project team members performing the work: it allowed the automatic reconciliation of expected CRFs with received CRFs. Previously, this reconciliation was a manual and time-intensive process; now it is fully automated, giving study monitors a valuable reason for keeping CTMS data current and thereby allowing management to make well-informed decisions regarding study monitoring and data management resources. Another way in which firms can extend the reach of this technology is by adapting it for use in all trial phases as soon as possible. Currently, most CROs limit their use of CTMS to phases II and III of clinical testing. However, PRA has been using it across all phases, including phase IV and even in some phase I trials. In the case of phase IV and late-phase testing,

PRA has made changes that actually simplify the system for very-highvolume trials with thousands of investigators and subjects—especially in the areas of managing the recruitment of investigators and managing the thousands of accounts and contacts needed to support the trial. In combination with the portal, the information delivery system was a focal point with a large client. The technology tools allowed PRA to keep track of potential subjects to enroll in a trial so that it was easy to identify the individuals coming in at different periods and hence notify the client. At the time, this functionality was not available within existing systems. However, PRA adapted the technology it had to suit those needs, coming up with the idea of web forms and using its portal and portal logs to keep track of this information, thereby making it possible to contact the client to keep them updated. Enhancements for the Future In the coming months, PRA will be expanding its project status review reporting capabilities to provide executives with an interactive reporting solution that presents key financial and operational metrics for each executive’s portfolio of projects. Using Siebel Analytics, executives will be presented with a dashboard that aggregates key performance indicators across client programs. Each dashboard will support drill-down functionality so that executives can very quickly ‘dig into’ metrics for individual projects and/or subject areas of interest to them. In the next year, PRA plans on integrating CTMS with its Cisco Enterprise Call Center software, providing a unified call center that will allow PRA employees to provide a higher level of service to their customers. The unified 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. Going forward with CTMS, it is important to look at the areas where it has succeeded and failed. It can prove difficult to integrate a successful system without forward planning—this can leave firms having to ‘make space’ for CTMS in their infrastructure, which may interfere with ongoing clinical trials and actually hinder workflow. Clinical Trial Management Systems— Past, Present, and Future PRA foresaw that CTMS technology would become increasingly useful as clinical trials became more complex and its client base grew, and it is this forethought that has enabled successful implementation of the technology. Furthermore, the implementation of a standardized infrastructure can reduce maintenance costs as a firm grows. Once in use, it is important to maximize your CTMS technology by trying to find new and different ways to use and adapt it for your needs, as demonstrated by the many examples in this article. At present, CTMS appears to be a technology that has now come into its own, proving to be an important enabling tool in the management of the large complex trials that have become increasingly common. However, it is not enough simply to install the system—to maximize its value a company should be innovative and progressive, looking to exploit all of its systems to support its business. Looking ahead, it seems that this technology will only become more vital for progress as trials become larger and more complex, spanning more and more populations across the globe. ■

1.

Pratt T, The CTMS Story: Focusing on Need, Applied Clinical Trials, 2006.

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CTMS in the Wild

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 research organization (ARO) in the world. It combines clinical expertise and academic excellence with the full-service operational capabilities of a major contract research organization (CRO). The DCRI operates with an approximate 50/50 balance between government-sponsored clinical trials and industry-sponsored clinical trials, in addition to our academic work, which makes us a niche player in the clinical trial arena. One of the benefits of the CRO-type offering from an institution such as the DCRI is that we have an academic aspect to our work. We have a real desire to understand the research, understand what the data are saying, and work out how that affects the patient. This attitude can be plainly seen in different meetings, in the hallways, and within the DCRI in general: there is a huge focus on patient care, which is the end goal of every clinical trial.

CTMS. In parallel, we initiated a project to identify all trials that were using the previous programs and, with the aid of a specially designed matrix, determined the ones that were candidates for migration to CTMS. Some projects were left to simply run out their life-cycle within the old system, while we actively migrated others—at least 10 projects—to CTMS. We are now at a point where we are 100% using CTMS, and the previous tools have been retired. With the one, holistic product we now have a much higher competency center, so if end-users have issues they call my team and we are able to answer their questions. Furthermore, within the clinical operations organization, because everyone is using the same product you can get immediate help from the person sitting next to you. There are five distinct areas where the CTMS has provided benefits to the DCRI. Single Source of Information

My role is a Line of Business Owner: essentially, I represent the business and the business needs. I am the day-to-day decision-maker on what we do with our clinical trial management system (CTMS) from Siebel (now part of Oracle). I co-ordinate with the Director of Clinical Operations. Together with the Information Technology (IT) Product Manager, I am responsible for growing and enhancing the product within the DCRI. The Business Value of the Clinical Trial Management System We have officially been using the CTMS for a little over two years for all new projects. Pre-CTMS, we were using two different programs that had been written in-house to capture the same type of information, both of which were in a production environment, and as such it was difficult to support and build on the programs. We started out by introducing CTMS in a couple of test projects in a pilot phase. Once that was deemed successful, we rolled it out across the organization, and since then all new projects have had to use

The CTMS is our single source of all trial information relating to site management and monitoring, and is useful in helping us get an understanding of how long it takes for sites to become active and to start enrollment. Once enrollment is under way the system can also help us keep track of enrollment trends, how sites have performed, and how we have performed in reaching enrollment goals. Such historical information is crucial for successful future trial planning. When the DCRI is starting up a new study with specified parameters, it is important that my team is able to provide the data that make it possible to compare the new study with similar trials that have already been completed. Timing is the hardest thing to factor in, as it is so variable among trials. There are large and small trials, long and short trials; some trials run fairly close to schedule, while some undergo a change in scope that causes them to run over time. Trying to make sense of all of the data is a very complex job. It has been made easier with the advent of CTMS because we can query the data, filter them, and then receive a report. Previously, we would run a series of separate reports, which were then combined in a spreadsheet for manual analysis.

Kevin Jarrell is a Project Leader for the Duke Clinical Research Institute’s (DCRI’s) clinical trial management system (CTMS). He joined the DCRI in 2007, and since joining the CTMS team he has led several successful major and minor releases/upgrades to CTMS. In addition to managing the day-to-day support team, he is actively planning future development to align with the strategic direction of the DCRI. Mr Jarrell started his career as a Laboratory Technologist in the genetics laboratory of a major central laboratory. He then changed industries and began working at a major clinical research organization as a Clinical Research Associate and Clinical Trainer, before switching departments to become a Senior Information Technology Business Analyst, focusing on improving the company’s CTMS. He received a BSc in biology from Longwood College, Farmville, Virginia.

Standardization One of the strengths of the product is that it allows us to implement a standard framework, yet in some areas there is an inherent flexibility that we can customize for each trial. Therefore, we can have a standard framework for the whole organization, yet still be able to cope with the unique aspects presented by each trial. The functionality across the trials is fundamentally the same: we can track sites, track milestones within sites, create conversation logs for the sites, record site visits, and make trip reports. Where the flexibility comes in is that with certain trials we may want, for instance, five milestones, while

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CTMS in the Wild

for another trial we may want 10, and for a third trial we may require 30. Moreover, one trial may need conversation logs while others do not. Similarly, we can specify the number of documents required per trial, and so on. Essentially, for each trial we can determine how much or how little of each item it needs or the trial team wants to use. Of course, standardization—for example standard terminology and definitions— sometimes brings its own restrictions. There are always rare examples where one particular group will need something very different from the norm, and that is always a challenge. It is a balancing act, trying to meet the needs of the 90% without excluding the needs of the 10%. Regular Upgrades With the CTMS platform, we have been able to structure our software development life-cycle in such a way that we can put out new functionality every three to four months. This means that if the endusers identify something they would like to change, we are able to turn that around fairly quickly and get their enhancement request back to them. There have been elements that the product has not provided that we have added in. For instance, we have done a lot of work around our trip reports, including adding the capability for electronic signatures and adding new sections of information. We have also added fields to existing data components or pick lists and segregated data so that only certain users can see them. While this is implicit in the role-based security that the system offers, we have also added extra security. Accounting for Cost The labor costs in terms of running and maintaining CTMS are treated as an infrastructure expense. Now that we have implemented the product, we are in the maintenance and ongoing enhancement mode. This means that for development, as we follow the software development life-cycle, we do not have to go back to the Technology Steering Committee and request more funds. We are able to dedicate staff to the CTMS product and continue to build or enhance it. Using this structure, we have been able to build up the product very quickly.

Enhanced Efficiency The main savings we have realized using CTMS have been in terms of operational efficiency. The Siebel eClinical product is web-enabled, and we have also made it HTTPS-secure so that our monitors can access it from virtually anywhere. As a general rule, people are much more accustomed to a web interface than to any bespoke program, and the layout appears logical to them. Using a standard Internet browser, users can access the system, enter data, run reports, and obtain information, which was not possible before. The response time is good, so it is possible to move around the system and enter data, as well as generating reports, so that management can make decisions. The major time savings we have seen so far have been around enabling the decision-maker. Having a single place, standard definitions, and standard ways to enter data, allowing all of the different trial team members to put their data into one place, and then being able to run

The major time savings we have seen so far have been around enabling the decision-maker.

reports on the data, have probably been the areas where we have seen the greatest time savings and the most efficiency. Regardless of the interface, it still takes a clinical research associate the same amount of time to type up a trip report, and there is not a tremendous amount of time saved regarding most of the day-to-day routine tasks. Nevertheless, having a tool that users go to every day and become accustomed to and proficient with in itself generates efficiency: if a task can be completed more quickly, it frees up time to do something else. Future Directions The true benefit we have derived from this system is our ability to configure it and customize it for our individual business needs. This has allowed us to integrate and automate some aspects of our business that are unique to us. This is the aspect that will occupy us over the next couple of years: trying to ingrain CTMS into our business and into our business processes, and in so doing further maximizing our investment. Having the eClinical product built around our business needs has

It is a balancing act, trying to meet the needs of the 90% without excluding the needs of the 10%.

Targeted User Groups For each new release or upgrade we try to target a primary user group. While there may be other enhancements that may fit the needs of many other groups, from our perspective the best way to implement an upgrade is to focus mainly on just one user group and deliver something significant to them.

proved very supportive. We are mindful of what else we could do with the extended functionality, and there are high-level discussions around where our business could go, but we do not want to be in a position where the software drives the business. Therefore, so far, implementing CTMS has not changed our services. Most of the advantages we have achieved are due to the good

At the DCRI there are various user groups, including those that deal with site management, site monitoring, safety, and data management; groups that are responsible for business administration and liaising with sponsors; a management team that runs the clinical operations organization; a contracts group; and a group that deals with the regulatory side.

collaborative working relationship we have at the DCRI between the business and IT sides of the organization. Both sides are in alignment in wanting to do the best we can for the organization, which is not always the case. Working on a unifying project such as this has helped cement that relationship, and will hopefully create new ones further down the line. ■

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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 unprecedented pressures on multiple fronts. Drug development costs continue to spiral upwards, there is increasing generic competition, pipelines are shrinking, and there are pricing pressures from healthcare providers. So, it is no surprise that the industry watchwords in these turbulent times are efficiency, accountability, and control. Based on its experience, Accenture believes that biopharmaceutical companies on the path to achieving high performance not only need to keep costs contained but also need to ensure accountability of expenditure. Thus, more companies are embracing technological solutions to help manage their portfolio of developmental projects as well as to execute their clinical trials in an efficient and controlled manner. This article discusses some of the major information technology (IT) trends that have affected and will continue to affect the biopharmaceutical world, and examines the role of clinical trial management systems (CTMS) within this environment. Industry Trends The number of industry-sponsored clinical trials has been steadily rising in recent years. Investigational New Drug submissions at the US Food and Drug Administration (FDA) have increased from 542 in 2004 to 662 in 2007—a 22% increase.1 Not only are there more trials today, but there is also a trend of an increasing number of patients per trial. Trials are also becoming more complex and require a higher statistical power to prove safety, specifically in those areas where new products are targeted to major populations. Coupled with the related trend for the biopharmaceutical industry to tackle more novel, multifactorial diseases, this all points to trials of greater complexity and longer duration. Furthermore, FDA figures show that the number of new drug approvals has been in general decline since the mid1990s: only 18 innovative new drugs were approved in 2007 (see Figure 1). Micro Trends Paradoxically, for an industry that is often at the forefront of scientific discoveries, the biopharmaceutical sector in general has been a slow adopter of new IT. Electronic data capture (EDC) technology began to be

implemented nearly two decades ago. From these early beginnings, it was expected that clinical trial data collection and management would rapidly evolve from a paper-based system to an electronic environment, with more than 50% of trials being performed using EDC within two to three years. The reality is that, due to several factors, progress has been very slow, and it is only in the last two years that Accenture has seen the true adoption of the new model for data acquisition and management. Many in the biopharmaceutical industry can now see the value and importance of effective IT and how it can help drive high performance in an organization. However, the need to invest significant capital in enabling software or technology has been another major barrier to the implementation of effective IT initiatives. To overcome this obstacle there has been a shift away from large single capital investments—often in the range of $20–30 million—toward making IT investment part of the annual expenditure budget. Companies now look to purchase software or technology using different financial models that have had a significant impact on the application landscape. Application service provider models, or one-time/per-study/per-site contracting, are examples of these flexible approaches to financing clinical trial technology. We have seen how these new models allow biopharmaceutical companies to regulate cash flow and, critically, to significantly reduce large capital investments. The biopharmaceutical companies are still, in effect, making the same investment in terms of overall expenditure, but the new models give companies flexibility in their overall budgeting process and, importantly, are reflected in the figures that are presented to the financial markets. Macro Trends On the macro level, there has been a major change within the industry in the way in which biopharmaceutical companies regard R&D. In previous decades, the early research phases were perceived purely as a means to generate innovation and create pipelines. With the considerable decline of productivity across the pharmaceutical industry, coupled with a near twofold increase in spending over the last seven years (see Figure 1), it has become essential that R&D be managed with a business-like approach. Effective clinical trial management and operational efficiency need to be at the forefront of clinical operations organizations. Consequently, R&D is, for the first time, being held accountable for its budget. It is critical for R&D to cut costs while delivering the same (or greater) number of trials. The heads of R&D of many biopharmaceutical companies have been asked for $100–300 million in cost reductions to contribute to $1–2 billion cost-cutting objectives for the whole corporation. For example, Bristol-Myers Squibb began 2007 by promising $600 million in cost savings, added another $1.5 billion in December 2007, and has recently added another $1 billion.2 Wyeth,3 Merck & Co,4 Pfizer,5 and Novartis6 have announced similar cuts in expenditures.

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: henry.d.levy@accenture.com

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Impact on Research and Development Accenture realizes that the trends discussed previously will have an impact on the R&D activities of biopharmaceutical firms. One major effect will be rationalization—of pipelines, clinical trials, and patients. At the highest level, this rationalization will result in a reduction in the number of trials: companies will have to decide what the focus of their pipeline is and make some difficult decisions about which trials to conduct. Adaptive trial design will come to the fore as it will allow companies to optimize ongoing clinical trials. We also anticipate that companies will reduce the number of trials run in parallel for a single product. For example, a company with an oncology drug that had shown promise in treating both head and neck cancer and pancreatic cancer would previously have tested the candidate drug in both indications at the same time. The strategy now is to focus: pursue the indication that either has the best chance of obtaining approval or that will recognize the best value. Obtaining a first approval improves the likelihood of getting subsequent approvals. The trends will also promote outsourcing, specifically the need to define new models for optimizing resources in India, China, and Eastern Europe. Outsourcing can potentially achieve a 30–40% reduction in the cost of non-core components such as clinical data management, document management, IT, and application management, and can even reduce certain costs related to pharmacovigilance and regulatory submissions. Depending on the company, between 3 and 7% of R&D costs may reflect such non-core elements. Crucial Drivers For biopharmaceutical companies to meet the objectives of increasing clinical trial throughput and reducing costs, Accenture sees the need for improvement on several fronts, including control, operational efficiency— with a goal of reaching operational excellence—and better decisionmaking. Clinical trial management technologies play a central role in providing these capabilities to evolving development organizations. Control Go to any biopharmaceutical company today and ask the question: In each therapeutic area, how many trials are you running, and how many are in phase I, phase II, phase III, or phase IV? Typically, nine out of 10 companies would take several days to collect and provide that information, and in most cases the data would be inaccurate. The data may be late or out of date, or based on information derived from strategic plans rather than from actual executed plans. This problem is endemic and can be seen at multiple levels: the number of sites that a company has active at any one time, the number of qualified investigators available to conduct the trials, the number of required certified laboratories— essentially anything related to control over the clinical trial portfolio. These discrepancies can represent organizational, technological, local, or global issues. A company may have control over individual pieces of the clinical trial process, but not consistent and comprehensive control—and without that the company lacks the ability to manage its resources effectively. The need for control is a principal reason for implementing a CTMS such as the Siebel Clinical from Oracle. Siebel Clinical’s origins in sales force automation and customer relationship management provide flexibility in helping companies manage different types of trial. This kind of highly reach a ‘kill’ decision regarding trials more quickly, and can also help

Figure 1: Research and Development Spend versus New Drug Approvals
40 35 30 35 25 No of NMEs 20 15 10 10 5 0 5 0 R&D spend $bn 30 25 20 15 50 45 40

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2003 Total NMEs

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2005

2006

2007

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.

customizable, highly configurable CTMS—one that is able to manage different types of environment, from pre-marketing trials to phase IV post-marketing studies or country-specific accounts—offers a control system that can effectively manage disparate resources. Operational Excellence Operational efficiency—with the ultimate goal of operational excellence— is essential for proper execution of clinical trials. Achieving operational excellence requires a clear plan and knowledge of both the critical milestones and the relevant dependencies. Effective management of a project as complex as a clinical trial requires access to accurate reports that detail the daily status of patient enrollment, updates on how much new data has been gathered and cleaned, key dependencies on regulatory approvals at the site, and the status of payments to the investigator site. With this information, the heads of clinical development can develop an understanding of their workload within the context of their whole trial portfolio and manage their trial and submissions timelines effectively. With proper resource and project management capabilities, the development organization is able to manage its resources effectively and nimbly reallocate resources as projects are cancelled or as priorities change. Decision-making Accenture believes that data analytics can add significant value to improving or optimizing decision-making, while also making the decisionmaking process more strategic. Taking advantage of current and historical data allows a development manager to be more proactive; through modeling and simulation he or she can predict the success of upcoming trials and therefore adjust, in advance, either the design of the trial or the method by which it is executed to reach the optimal level of performance. This predictive capability is achieved by examining the data from, for example, the performance of one investigator over the last five years, combined with knowledge about the relationship between the clinical trial sponsor and that investigator. In addition, historical siteperformance data across enrollment, quality of data delivered, compliance, and specific patient populations can increase the success rates of a site in a clinical trial. As we look forward, we see that coupling

ECLINICAL VISIONS

15

High Performance The Place of CTMS
of this existing information with new sources such as payer or prescription data can further improve trial execution. Within a CTMS, a pre-defined analytics data model coupled with a supporting technology platform for mining complex data are now critical parts of the decision-making process for system selections and are key differentiators for those vendors that can provide an off-the-shelf analytics capability. Future Perspectives Critical Factors for Achieving High Performance Even after selecting an appropriate CTMS vendor, companies face many pitfalls that can cause delay, increase costs, influence adoption, and, sometimes, lead to failed projects. Critical factors related to avoiding these pitfalls and achieving high performance include the ability to manage scope and avoid excessive customization, and avoiding the overintegration of CTMS capabilities with point-to-point interfaces rather than leveraging a service-oriented architecture. However, the most common reasons for suboptimal implementation of CTMS solutions relate to a lack of balance between system implementation and process or organizational change during the implementation, and to poor adoption and lack of quality data after roll-out. Business Integration versus Systems Integration Implementing a CTMS is never a solution in and of itself. Appropriate processes and the right organizational support model must be in place if the technology is to truly enable high performance. In successful implementations the focus is on business integration, not just systems integration. Achieving high performance starts with determining business needs and its current processes, identifying the appropriate operating model, and then using technology as an enabler, not as the main solution. The complexities of data analytics mean that there is more to the process than simply gathering and manipulating vast quantities of data. Many companies gather and store large amounts of data, yet use only 5–10% of this valuable database. This is a huge investment in data that will never be used. Accenture believes that, in order to achieve a ‘higher state of awareness,’ companies must do more than simply experiment with techniques and hope for a positive end result. Biopharmaceutical companies must understand good methodology in terms of data analytics: to observe what is happening, make a determination, develop theories, and then understand what the actual questions are that must be answered. This type of fundamental scientific thinking is critical before data analytics can be utilized effectively. By starting with the question to be answered before collating the actual data and performing meaningful analytics, companies can create a feedback loop that might allow for the discovery of some of the unknowns in the equation. How to Keep Good Data One of the biggest challenges companies face when installing a new system is ensuring the migration and maintenance of good, clean, up-to-date, quality data. This is a particular problem for larger biopharmaceutical companies with vast amounts of legacy data. An investigator database at any company potentially contains as many as
About Accenture Accenture is a global management consulting, technology services, and outsourcing company. Combining unparalleled experience, comprehensive capabilities across all 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 clients in over 120 countries, the company generated net revenues of $23.39 billion for the fiscal year ended August 31, 2008. Its home page is www.accenture.com ■ About Accenture’s Health & Life Sciences Group Accenture’s Health & Life Sciences professionals deliver innovation and insight to both the private and public sectors of the marketplace, including integrated healthcare providers, health insurers, managed care organizations, public health organizations, and pharmaceutical, biotechnology, and medical products companies. With more than 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, including 25 of the 27 healthcare and pharmaceuticals companies in the FORTUNE® Global 500. Its home page is www.accenture.com/h&ls

10–20% duplicate entries. This inability to distinguish whether the data are clean will hamper new implementations, or at least significantly decrease the value of them. Keeping good data requires intervention. This can be achieved by providing appropriate data visibility to multiple layers of the host organization, including development leaders. Similarly, exposing the data to sites accessible through investigator portals can stimulate compliance with data quality initiatives.

Accenture

recognizes

that

the

main

challenge

now

facing

biopharmaceutical firms is how to do more—or at least the same—with less, which entails driving productivity and reducing costs. Therefore, maximizing the value of data, including clinical and trial management data, will be a critical part of development organizations’ objectives. At the top of the agenda for all R&D leaders who seek high performance is development and enforcement of discipline concerning effective data capture, maintenance, and analysis. This will enable decision-makers to more effectively influence clinical trial design and strategic direction while taking a drug through the approval process. Current trial management and data analytics systems can provide companies with effective platforms for achieving better utilization of data. However, companies who seek to be high-performance businesses must also adapt their organizations and their cultures to take full advantage of the capabilities available to them, allowing them to be more competitive in the increasingly challenging and complex environment of the pharmaceutical future. ■ For more information on how Accenture can help you achieve high performance, contact Henry Levy at +1 267 216 1827 or henry.d.levy@accenture.com. For more information on Accenture’s High Performance Business research initiative, visit www.accenture.com/global/High_Performance_Business

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

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

16

ECLINICAL VISIONS

eClinical Visions

HEALTH SCIENCES

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 Centre (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
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