August

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1 Innovative Technology Provides Seamless Data Integration Linking Clinical Trial Patient Data to Central Laboratory Data Via an Oracle -Based Exchange Platform August

2 Introduction Drug developers are struggling to improve efficiencies in the clinical drug development process. The need is urgent: on average, it still costs more than $1 billion and takes more than seven years to conduct clinical trials and win approval to market a new drug. 1 In addition, increased complexity in protocol design and execution burden have demonstrated a dramatic impact on extending study cycle times, raising study budgets and challenging investigative sites and study volunteer participation. 2 The development and application of new technologies is one of the most effective ways to reduce time and cost and to improve the quality of clinical data. This paper will discuss the efficiencies that can be achieved in data management using an innovative, automated platform that integrates patient data and central laboratory data in real time. Central to this improvement is the seamless interface achieved among drug sponsors and service providers. Outsourcing, an integral strategy in pharma s efforts to speed new products to market, has proven benefits in reducing clinical trial timelines. According to a 2008 report on the use of contract research organizations (CROs), outsourcing was associated with faster development times at comparable quality. High CRO usage projects achieved database lock two weeks earlier than low CRO usage projects. 3 Although partnering with CROs can increase efficiency, the selection of multiple providers also can slow operations, add complexity and increase potential for error. This is of special concern regarding operations across global clinical study sites and central laboratory services. It is common practice for pharmaceutical and biotechnology companies to select different providers for clinical trial management and central laboratory services. The transfer and integration of laboratory data with patient data is a time-intensive task that complicates and slows data management operations. Unique efficiencies can be achieved when the central laboratory and the CRO data vendor conduct realtime data management. Oracle -based Exchange Platform. PPD has developed and has extensive experience with a proprietary data exchange platform that distinguishes and integrates clinical site data and central laboratory data in real time. The platform is based on Oracle, the industry-leading data management system. Its key process features include: Nightly integration and reconciliation of data across laboratory and clinical data systems Exact match between clinical and laboratory data from day one of patient enrollment Constant data communication to provide realtime patient information exchange 2

3 Real-time integration of patient and laboratory data reduces risk of delay in database closure. This integrated model offers benefits including: Elimination of time-intensive tasks needed for data transfer Significant reduction in the data reconciliation cycle Earlier information to improve decision-making at the study site Figure 1. Oracle-based Exchange Platform SEAMLESS DATA INTEGRATION SPECIMENS TO DATA 3rd Party Data Central Lab Data SINGLE COMBINED GLOBAL DATABASE Clinical Data CLINICAL DATA CLEANED VIA SEAMLESS ELECTRONIC INTERFACE Risk minimization for data transfers Real-time query resolution Improved cycle time More complete data for interim analysis Faster data lock One Final Database 3

4 Central Laboratory and Clinical Trial Management: Stand-alone vs. Integrated Models Stand-alone model. In the current stand-alone model, patient data and laboratory data are collected separately throughout the course of a trial. Data from clinical trials sites, which consist of patient demographics and clinical measurements from patient visits, are captured on case report forms (CRFs). Central laboratory data, which consist of results of sample analyses (e.g. blood, urine), must be transferred to the CRO and integrated with CRF data. The two data sets then must be reconciled to eliminate discrepancies, errors and omissions. Before the database is closed at end of study, reconciliation of all integrated data must be reconfirmed. The process of integrating clinical and laboratory data is time-intensive and cumbersome. To merge the two data sets, transfers must take place at set intervals weekly or monthly, in most cases. Each transfer requires from two to six hours of preparation before transfer and an additional two to four hours to merge the data upon receipt of the transfer. When data are collected separately, CRF data may not be updated and reconciled with laboratory result data until the end of the study. End-of-study reconciliation of the data sets for each patient over the full duration of the study can take up to several weeks. This is frequently the cause of significant delays in database lock. Integrated Model Via Oracle-based Exchange Platform. To create an integrated model for patient and laboratory data management, PPD established a data portal between the central laboratory s Oracle database and the Oracle clinical database used to manage clinical data. This proprietary platform enables real-time, automated exchange of laboratory and clinical data sets. The Oracle-based exchange platform also enables sharing of laboratory-related discrepancies among staff to identify and address data reconciliation issues. In this integrated model, laboratory data is transferred into the clinical database daily and data are cleaned and reconciled in real time. Transfer time savings. The exchange platform eliminates the labor-intensive process of data transfer. It eliminates the set-up time for transfers, which requires up to 100 hours in the course of a trial. It also eliminates the four- to eight-hour total transfer time, which typically saves from 100 to 200 work hours over the lifetime of a trial. The potential for transfer format errors is eliminated as well. Reconciliation time savings. The typical cycle for data reconciliation usually involves at least six interactions between the study site, central laboratory, and CRO and takes a minimum of 10 days to complete. Every study experiences numerous issues that require more than one cycle to resolve. The Oraclebased exchange platform eliminates two days from the reconciliation cycle, a 20 percent reduction in time. 4

5 Earlier query and resolution with sites. A major issue for drug developers is the need to confirm data points with the clinical sites quickly so that the query process can begin while patient visits are still fresh in the investigator s mind and before investigator notes have been archived. Rapid query resolution is important to ensure data quality. Delay in query resolution is a common problem; in some cases, queries are not resolved for months after a patient visit, which dramatically increases the possibility for wrong conclusions. An important benefit of the integrated data model is that it enables review of data extremely close to collection time. This also eliminates the bolus of data reconciliation that must be done at the end of the study when review and reconciliation have been delayed. Estimated cost savings. Based on PPD s experience, the cost savings achieved by the integrated data model are on the order of tens of thousands of dollars for an individual study. The less quantifiable and, arguably, more significant measure is the reduction of risk to study closure achieved as a result of reduced cycle time and elimination of transfer/reconciliation cycles on the critical path to database lock. Integrated Model Experience PPD launched the exchange platform in June Experience includes 53 studies in a wide variety of indications, involving more than two million CRF pages. The time and cost savings achieved by eliminating the need to send and receive transmissions average 175 hours per study. Even greater time reduction as much as 200 hours per study results from more efficient query resolution. In the traditional stand-alone model, there are typically six physical handoffs of study data for every reconciliation cycle; a typical reconciliation cycle requires a minimum of 10 days. The Oracle-based exchange platform eliminates two days from the 10-day reconciliation cycle, assuming that transfer occurs on Day 3. At Day 5, the query resolution process typically adds seven to 14 days, and from one to two additional days at database lock. 5

6 See the comparison of the traditional stand-alone model and integrated data model below. Figure 2. Sample Collection Cycle in Days: Stand-alone Model Figure 3. Sample Collection Cycle in Days: Integrated Model Day 0 Sample collected; overnight to lab Day 0 Sample collected; overnight to lab Day 1 Lab processes sample (validation/qc) Day 1 Lab processes sample (validation/ QC); data released to CRO; reconciled Day 2+ Data transfer (timing relative to transfer schedule) Day 2 Queries issued Day 3 Data reconciliation Day 3+ Queries resolved at site and returned to CRO Day 4 Queries issued Day 4 Queries acted upon; lab enacts data corrections; data released to CRO; reconciled Day 5+ Queries resolved at site and returned to CRO Day 5 Data complete; or initiate query cycle again Day 6 Queries acted upon; lab data issues collected/communicated to lab Day 7 Lab enacts data corrections Day 8 Data transfer Day 9 Data reconciliation Day 10 Data complete; or initiate query cycle again 6

7 The most important benefit has been on-time closure of the study database. Delays due to outstanding query resolution which typically cause a project to lose two or more days at end-of-study are eliminated by the new reconciliation process. The integrated model also provided operational benefits for the drug sponsor. Benefits included: Operations staff had to learn only one system: Interactive database sets provide more clean/complete data due to rapid query resolution and data release Final data recipient receives a single database Contracts and budgets for two services are combined into one There is one point of communication (the CRO) rather than two (lab and CRO) Future Applications The success of the Oracle-based exchange platform points to efficiencies that could be achieved by similar data integration strategies. Today s drug development pipeline is dominated by oncology therapies, and a large percentage of oncology studies use local rather than central laboratory services. This suggests an opportunity to expand the Oracle- based exchange platform to allow highly specialized patient and result data from local laboratories to be entered into the central laboratory database. These data could then be harmonized and managed through the exchange platform to provide a single combined dataset. Another opportunity would be a similar expansion to integrate laboratory sample storage or specimen lifecycle management information. References 1 Tufts Center for the Study of Drug Development. Outlook 2010, January Tufts Center for the Study of Drug Development. Rising protocol complexity, execution burden varies widely by phase and TA. Impact Report, Vol. 12, No.3, May/June Tufts Center for the Study of Drug Development. R & D Management Report, Strategic Outsourcing and Global Drug Development, Vol. 3, No.2, March Pharmaceutical Product Development, Inc. All rights reserved. PPD is a trademark of PPD. Other marks are the property of their respective owners. 7