Medidata s Approach to Today s Drug Development Dilemmas

WHITE PAPER Medidata s Approach to Today s Drug Development Dilemmas Optimizing Clinical Trials: Concept to Conclusion

Abstract Biopharmaceutical and medical device companies today operate in a drastically different environment than they did just ten years ago. Pricing pressures, patent expiry and increasing regulatory burdens are compounded by advances in trial complexity, exponential increases in data volumes and continued enrollment challenges, all within an uncertain macroeconomic environment. Organizations must strive for productivity improvements in all functions. For clinical researchers, this translates into pressure for shortened trial timelines and reduced budgets, while maintaining or increasing quality and transparency. For decades software applications have been available that focused on specific functions of the clinical trials process. They automated the tasks at hand, gaining low-hanging efficiencies but without challenging the underlying processes and functional overlaps of the siloed approach to clinical development. Today s competitive biopharmaceutical environment demands more than the automation of technical point solutions, more even than the integrated suite of some connected applications that simply support discrete activities. Today s environment requires the holistic integration of technologies to drive continuous process improvement and exponential gains in productivity, enabling the technology to transform the value proposition of the clinical research process itself. The benefits of such an approach go beyond the elimination of redundant tasks with their multiple associated reconciliations, to the optimization of the clinical trial through enhanced collaboration, transparency and work flow, more effective decision making based on comprehensive and timely analytics, and a lower total cost of clinical development. This white paper describes the challenges associated with the current environment and the limitations imposed by today s commonly used clinical research point solution technologies. It outlines Medidata Solution s approach to unifying clinical development and clinical trial execution through a single clinical technology platform that addresses clinical research needs from trial concept to conclusion. Background Clinical development begins with a scientific rationale that is translated into a business strategy, which is then transformed into a clinical strategy. This clinical strategy is refined to a specific operational plan of clinical programs. These clinical programs consist of numerous trials designed to support regulatory submissions by proving the efficacy and safety of the therapy. From the conceptualization of the clinical trial through protocol design, to data generation, capture and analysis, are a set of processes governed by numerous regulations and operational requirements. These processes are executed by scientists, physicians, data managers and administrators, using standard operating procedures, company and industry guidelines, and supporting technologies. Research teams charged with bringing drugs and other treatments to market face a well-known litany of challenges: patent expirations, intense competition, complex regulatory requirements, safety and quality concerns, media scrutiny. Meanwhile, clinical trials are growing in duration and complexity with larger numbers of observations per subject, multiplying requirements for both surrogate and end point evaluations and increasing challenges in recruitment of both investigators and subjects. Additionally, the externalization of R&D, characterized by increased outsourcing and partnering, continues to drive the need for industry-wide operability. By way of example, the typical late stage oncology study or outcomes study may draw on hundreds of site investigators, each with their own training and input needs, and a litany of additional other stakeholders in a number of separate operations, funding and review organizations. Medidata Solutions Worldwide 3

4 MEDIDATA S APPROACH TO TODAY S DRUG DEVELOPMENT DILEMMAS All of these multiple touch points serve to exacerbate long-standing bottlenecks in clinical trials, such as limited visibility into study metrics and benchmarks, incomplete transparency of trial progress across organizations and lack of collaborative platforms. The Problem Computer solutions and the Internet have greatly advanced the clinical development process. Software applications have automated portions of the clinical trial, taking over from telephones, paper forms and fax machines. While not yet universally adopted, computer applications have made major inroads in adoption by large firms and contract research organizations (CROs), with clinical data management (CDM), electronic data capture (EDC), telephone-based randomization systems and statistical analysis systems leading the way. These technologies have been important, but not yet transformative. The past decade has seen the evolution of technologies that automate existing processes, nudging work processes into new pathways and accelerating legacy processes, but generally maintaining the existing functional and organizational barriers in clinical development. Software applications supporting clinical research typically address the needs of individual functions, operating within functional silos with a lack of system alignment, forcing multiple inputs of the same data and requiring the learning and maintaining of different interfaces. These applications often lack consideration of other functions needs and system inputs, inhibiting collaboration and reinforcing role-based boundaries between professionals. The need for large amounts of computing power has not yet been reconciled with individual work streams for a unified and smooth trial research process. Frustrations with current applications include: Lack of a single source of the truth, with information inaccessible in any one place, making it difficult for managers to get comprehensive trial information, such as a complete view of patient status and history, investigator site performance and clinical development program status, and ensuring that all stakeholders are looking at the same data. Non-intuitive and obtuse interfaces. As easy as it is for vendors to use the term easy to use, few clinical applications are as easy to use as consumer web solutions, such as Google or Amazon. Incompatible systems, not based on industry standards. The lack of interoperability results in differing entry points, frequently requiring entry or transcription of the same data into each system or else yielding incompatible spreadsheet uploads, with subsequent need for labor-intensive data reconciliation. Systems sold by one vendor that, although billed as integrated, require behind-the-scenes customization and associated professional fees. In addition, these are mostly only internally integrated, not based on industry standards, requiring an all-or-nothing purchase. Lack of universal or industry operational standards that can be used to facilitate easy reporting and tracking of operational data. Applications that still require customization for individual needs leading to costly vendor-provided implementation personnel. Delays in data availability, with much data not available in (or near) real time. Besides the issues with the systems in front of them, clinical researchers continue to voice frustrations over what they are missing. Don t their smart phones instantly sync with their PCs? Can t they order anything from Amazon and get the receipt immediately? Can t financial websites take their savings account data and tell them what more they need to save?

Part of a wish list from users would include: Single System, Single Window One place to go to access everything about the trials they are working on, with one sign-in. Platforms that foster collaboration both within and outside the organization making communication easier, not harder, while still maintaining security. Systems that can help the team by highlighting best practices and business process streamlining. Ways to measure the costs of, and assign value to, various aspects of clinical development (e.g., the third EKG in a trial at each investigator site versus the value to be gained from the information). Applications that can tell how the trial is running from the clinical information that is being entered, and highlight the results as needed for senior management or ground-level team members. Quick but secure ways to get investigators trained and start enrolling subjects into the study. Any way to make investigators lives easier, to maintain investigator satisfaction and longevity. Help with training, easy query response systems, handy task lists anything that can help the site team members. The Medidata Approach Medidata Solutions, a leading clinical technology vendor, addresses the clinical development process with a range of Software-as-a-Service (SaaS) tools that individually deliver efficiencies and data-driven insights for optimizing clinical trials, and that together enable comprehensive processes that bring additional efficiencies and enhanced decision making to customers. Medidata is committed to enhancing and streamlining trials from start to finish beginning with conceptualizing the clinical trial with protocol design, through execution and management of the clinical trial, to conclusion with actionable data. Medidata s products, built around a common product strategy and infrastructure and focused on the singular needs of the user, have evolved as the leading platform in the industry by enabling a holistic clinical research process. The benefits for customers are enhanced user satisfaction, elimination of redundant tasks, enhanced collaboration and more effective decision making based on comprehensive and timely data, resulting in faster times to go/no go and a lower total cost of clinical development. Making this a reality requires Medidata to understand detailed clinical research workflows and enable a unified, highly interoperable and scalable architecture. Building on an understanding of the total clinical research endeavor, its goals and requirements, Medidata innovation leapfrogs from current best-in-class efficiencies to new paradigms, engineering an interoperable, comprehensive tool set that serves not just to automate point solutions but to create new processes that span functional roles and produce novel efficiencies. Medidata provides its solutions as SaaS, eliminating the need for expensive and burdensome customer installations, reducing versioning times and enabling rapid new functionality improvements. As configurable applications, each tool is flexible enough to match individual companies workflows, local requirements and preferences with the ability to embody best practices into the software and user interface. Customer preferences are accommodated along the continuum of total individual configuration to best practice-based pre-configurations and standards-based options. Medidata Solutions Worldwide 5

6 MEDIDATA S APPROACH TO TODAY S DRUG DEVELOPMENT DILEMMAS Medidata s solutions can be used singly to provide best-in-class efficiencies and process optimization, and can also be used with other Medidata features and products to create new pathways for clinical research. The diagram below shows the key areas of clinical research and highlights Medidata product roles, which are described in further detail below. MEDIDATA CLINICAL DEVELOPMENT PLATFORM Resource Management Strategy & Planning Build & Setup Execution Clinical Business Analytics Study & Protocol Design Randomization & Trial Supply Management Trial Planning & Budgeting EDC/CDMS Contracting Site Negotiation EDC/CDM Platform Targeted SDV Study Build Safety Gateway Outsourced Trial Planning Global Library Reports and Extracts Medical Coding Clinical Trial Management Predicted Recruitment Trip Monitoring Site Payments Clinical Management Portal elearning Legacy/Third-party Systems

OPTIMIZING Strategic and Operational Decision Making Medidata Insights, clinical business analytics, enhances strategic and operational decision making through the clinical trial life cycle from initial strategy and planning through execution and close with its unique combination of analytics based on company metrics and benchmarks drawn from peer industry players. The increasing pressure to improve clinical research processes requires new ways to measure and track individual study, program and therapeutic area progress. Medidata Insights addresses this by providing data-driven analysis of metrics derived from Medidata s Insights database of thousands of clinical trials from a broad range of sponsors, against which users can measure their organizations, programs and trials, focusing on similar categories or broader comparisons. Medidata Insights foundation is embedded in Medidata products. There is no additional system to install, and start-up of this solution can be accomplished in weeks. This context-based view of the clinical research process available through Medidata Insights is used to prompt operational improvement as well as to support strategic examination to reshape development programs, from concept to conclusion. OPTIMIZING Resource Management Medidata offers tools for budgeting, forecasting and managing resources throughout a trial, from up-front resource allocation through negotiations to tracking. These products include Medidata Grants Manager, the industry-leading application for trial planning and budgeting, which uses industry-based negotiated site cost information through exclusive access to the PICAS database of over 260,000 negotiated site grants to help develop targeted investigator site budgets; and Medidata CRO Contractor for outsourced trial planning, which uses the CROCAS industry database to identify and budget appropriate outsourcing strategies. Medidata CTMS (clinical trial management system), a SaaS-based approach for enterprise clinical trial management, supports faster time to value from planning through execution with robust tools for setting targets across key milestones, time and expenses, monitoring visits and patient recruitment. For example, the Clinical Payments module automatically translates study milestones to site payments, alleviating a key bottleneck in trials and increasing site satisfaction. Efficient, targeted source data verification (SDV) is supported by Rave Targeted SDV. This module provides sponsors and CROs with an EDC-based, scalable and auditable solution to plan and execute partial (less than 100%) SDV strategies within their regulatory framework. It empowers researchers to implement a risk-based site monitoring approach that can potentially improve monitoring efficiencies without compromising data integrity. Medidata Designer, study and protocol design, provides unique perspective into the costs of clinical trials. Using industry benchmarks, Designer highlights the full trial costs of protocol elements such as subject and site population, visits and procedures providing a roadmap for understanding and identifying cost-generating areas. Customers realize additional resource control using the study parameters from Designer and benchmarked costs from Medidata Grants Manager to produce investigator site budgets ready for presentation to sites. OPTIMIZING Study Design & Strategy Medidata Designer, for study and protocol design, supports efficient, collaborative study design while providing insights for study optimization through industry benchmarks, and views of the impact on cost, timing and potential enrollment of differing study designs. Shaping a trial to focus only on relevant patient data not only reduces resources for the sponsor, but can also boost enrollment and increase safety by reducing invasive procedures for subjects. Medidata Solutions Worldwide 7

8 MEDIDATA S APPROACH TO TODAY S DRUG DEVELOPMENT DILEMMAS Medidata Balance, a next-generation randomization and trial supply management tool, enables development of randomization plans for trials, using state-of-the-art interactive simulation tools. Medidata Balance, which is also used for subject allocation and trial supply logistics, features user-enabled tools for creating sophisticated randomization methodologies, putting control of randomization plan development into the hands of the users and reducing the need for costly outside services. OPTIMIZING Study Start-Up Once the study design and protocol are set, the conduct of specific study elements site identification, electronic case report form (ecrf) development, system build, safety committee approvals, monitor planning, investigator enrollment, among many others are some of the most time-consuming activities in a clinical trial. Applications are available that offer functionality for specific tasks, but Medidata s platform brings a level of efficiency from individual products, and additional benefits from their interoperability and scalability. Grants Manager s Contracting module enables rapid and informed sitesponsor budget negotiations online. Medidata CTMS includes wide support for optimized study start-up, including an Institutional Review Board (IRB) module that provides improved control; visibility into the Central and Local Ethics Committees submissions process; and the ability to track regulatory document preparation and submission milestones. imedidata, the single access point to all applications for the study team, also provides administrative tools that enable users to manage their own accounts, sponsors to manage their studies and investigator sites to administer their information and user accounts. imedidata provides access to Medidata elearning, a pioneering online training environment that is based on users study-specific roles, and is an integral part of a Rave study providing instant access for users no matter where they are in the world. Once users successfully complete the web-based course and pass the online test, they are immediately enrolled in the trial, without further intervention by trial administrators. Sponsors retain control and visibility into investigators training, while the burdensome administrative tasks at study start-up are minimized. Medidata Designer accelerates design and set-up cycle time and improves standards compliance through the collaboration-enabling platform. Key clinical documents such as study outline and protocol can be automatically generated through the reuse of structured design information from previous studies or company guidelines. Researchers can effectively shorten design cycle time and improve standards and standard operating procedure (SOP) compliance through clinical libraries, centrally managed templates and concept lock. This information can also be used to automate EDC/CDM study setup, statistical analysis, system set-up and other systems, lowering risks associated with manual programming and interpretation of the protocol, reducing document management burden and streamlining trial execution through reuse of design information in downstream systems. Built into the Medidata Rave EDC/CDMS application is the Rave Architect study-build tool. It helps reduce the time and effort spent turning a protocol into a full electronic study by allowing study teams to easily configure ecrfs, sophisticated workflows and security access, data blinding, source document verification and review requirements, dictionary coding and complex edit checks, all via a point-and-click interface. In conjunction with its Global Library, it provides a powerful means of streamlining the process of building multiple studies, extending the benefits of electronic clinical trials by creating reusable assets, allowing sponsors to build a trial based on previous studies or parts of studies; or by utilizing a company standards repository, ensuring consistency in trial design and efficiency of data analysis.

Medidata Balance, with its sophisticated statistical simulation that runs via a user interface, eliminates the need to write code to implement the randomization system for the trial. After the design and parameters of the randomization methodology are set, randomization and clinical trial supply logistics screens are automatically deployed into Medidata Rave, available to the appropriate sites and other users based on their Rave-defined roles and responsibilities. With a study built in Medidata Rave, reflecting the medical team s intent as recorded in Medidata Designer, a randomization plan chosen from among the simulations run in Medidata Balance, and users qualified via elearning and with rights defined in imedidata, much of the preparation for trial execution has been completed. OPTIMIZING Trial Execution Medidata CTMS provides sponsors and CROs with a robust set of tools to track and optimize timelines, resource allocation, expenditures and site performance during the execution of clinical trials. The Core Trial Management module provides management, tracking and reporting on key study activities and timed deliverables from the study through the subject level. It provides a central point for the tracking of study status notes; project management information; and study staff, contractor, and customer and key lab information. Subject enrollment tracked information can either be manually entered against each site or automatically imported from Medidata Rave or other EDC systems. The Monitoring Report module provides a centralized, electronic facility to author, review, approve and publish monitoring reports, including checklists, notes, action items and report submission tracking. Configurable for site evaluation, monitoring and site close out visits help enforce company-specific SOPs. Forms can be automatically populated with EDC-captured data, removing the need for data reentry, and visit confirmation and follow-up letters are auto-generated, saving time and freeing up monitors to focus on more value-added activities. The Clinical Payments module addresses one of the industry s most inefficient processes: translation of study milestones to site-payments. Key study activities automatically generate financial transactions; for example, a monitoring visit automatically generates a client invoice transaction while a subject visit automatically generates a site payment transaction. Robust integration tools allow transactions to be sent directly to a finance system for automation of billing and payment events. Medidata Rave, used by 13 of the Top 15 global pharma companies, is the industry-leading system for capturing, managing and reporting clinical research data, designed to help life science companies optimize their research investments by efficiently streamlining the clinical trial process. A single platform supporting both EDC and robust CDMS functionality, Medidata Rave has the flexible design to support the breadth of any organization's clinical processes, as well as the unique aspects of individual clinical trials. The system flexes to each user s role, presenting only the information needed and allowed, with tools to guide users work and to guide queries and task resolution. Medidata Solutions began as an investigator-centered EDC tool; the original development team was made up of clinical researchers, who looked at the application not as a product to automate tasks they were assigned, but who focused on how to make the data capture process easier. Medidata maintains a strong focus on the usability of the EDC interface for sites, providing a modern, intuitive experience for today s research teams. Medidata s Rave Safety Gateway captures serious adverse information directly from the ecrf, eliminating duplicate entry and the resulting reconciliation requirements, and replacing paper-based faxed reporting and telephone reporting with an auditable, automatic system. It extracts relevant data from Rave into the defined standard for safety data E2B which is then imported by existing safety reporting systems to trigger safety reports. Medidata Solutions Worldwide 9

10 MEDIDATA S APPROACH TO TODAY S DRUG DEVELOPMENT DILEMMAS Medidata Coder, a web-based medical coding system, is a robust, flexible and easy-to-use coding solution. With powerful capabilities to code and search against standard or custom dictionaries, it manages coding requests through a configurable workflow and supports multiple synonym lists and dictionary versions with tools to facilitate migration. Medidata Coder integrates seamlessly with Medidata Rave out of the box and is also interoperable with any source systems using CDISC ODM industry standards or flat file formats. OPTIMIZING Interoperability Multiple applications are used in clinical research, and sponsors have specific preferences based on their own requirements and experience. To provide seamless integration of other systems with Medidata applications, Medidata Web Services APIs provide seamless data interchange over the web with other systems. These software equivalents of standard electrical wall sockets make connecting third-party applications with Medidata s software easy and repeatable. Furthermore, they facilitate systems working as one. Like equipping a television from one manufacturer with external speakers from another, the end user experiences an integrated system. Data collected directly from subjects and laboratory test results are frequently captured in specialty software systems. To allow investigators and trial personnel to easily review all data about a subject or a compound, it makes sense to have all subjects data available in one system. For systems using the Medidata Web Services APIs, this occurs as soon as the data is recorded in the source (original) system, appearing to a data reviewer as if the systems were one. Data collected in Rave can also be transmitted to other clinical research systems, eliminating the need to transcribe data and the risk of erroneous transcription. For example, data sent from Rave to another system can feed installed clinical trials management systems and populate analytics platforms and data warehouses. Sent data can be a full database or an incremental segment covering both clinical data and study metadata. No user action is needed to activate these fluid data movements. Medidata APIs are effective because they incorporate industry standards, including CDISC and CDASH. Medidata s support of these standards, along with an integration tool kit that Medidata makes available to sponsors and to third parties through the Medidata Developer Central program, is the basis for the growing number of clinical systems integrated with Medidata Rave. The goal of these tools and the associated programs is for sponsors to be able to build and evolve their own unique eclinical IT vision. OPTIMIZING Access Across the Trial imedidata, clinical management portal, is a single access point to all Medidata studies, applications and associated thirdparty programs, providing an easy, unified access with a single password and maximum security. imedidata also provides coordination and simplified administration for sponsors, CROs and clinical sites. It facilitates administrative processes that enable users to manage their own accounts, sponsors to manage their studies and investigator sites to administer their information and user accounts.

Medidata: Optimizing Clinical Trials from Concept to Conclusion Our view of clinical research as a singular process propels Medidata to provide technology to focus on business optimization and process simplification, rather than merely improving the efficiency of individual tasks. Medidata s platform supports a unified vision while allowing flexibility for incorporation of sponsor-defined best of breed applications and promoting user-defined success. Measuring performance, both intra-organizationally and cross-industry, highlights opportunities for continuous process improvement. Medidata s goal is holistic clinical program development, where data collection and use are optimized through safe, efficient and self-correcting processes; where operational insights are extracted from clinical data already collected and managed; and where operational and clinical information is continually fed back from study execution to portfolio planning to drive new efficiencies over time. Because Medidata platforms are built around a unified architecture and interoperable structure, our set of solutions provides unique pathways that create new processes and insights throughout a clinical trial. Combining knowledge of technologies capabilities with the totality of users requirements, Medidata has reexamined the conduct of trials. We offer a platform that supports our commitment, spanning concept to conclusion, to provide clinical trial sponsors the means to meet their mandate to be faster and more efficient. Medidata Solutions Worldwide 11

About Medidata Solutions Medidata Solutions is a leading global provider of SaaS clinical development solutions that enhance the efficiency of customers clinical trials. Medidata s advanced solutions lower the total cost of clinical development by optimizing clinical trials from concept to conclusion: from study and protocol design, trial planning and budgeting, site negotiation, clinical portal, trial management, randomization and trial supply management, clinical data capture and management, safety events capture, medical coding to business analytics. Our diverse life science customer base spans biopharmaceutical companies, medical device and diagnostic companies, academic and government institutions, CROs and other research organizations, and includes more than 20 of the top 25 global pharmaceutical companies as well as organizations of all sizes developing life-enhancing medical treatments and diagnostics. info@mdsol.com mdsol.com +1 877 511 4200 Optimizing Clinical Trials: Concept to Conclusion Trademarks are the property of their respective owners. Copyright Medidata Solutions, Inc. 2011 09/11 BUSINESS ANALYTICS STUDY & PROTOCOL DESIGN TRIAL MANAGEMENT, PLANNING & BUDGETING SITE NEGOTIATION RANDOMIZATION & TRIAL SUPPLY MANAGEMENT EDC/CDM MONITORING SAE CAPTURE CODING CLINICAL PORTAL