clinical Trials - A Need for Organisational Change

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1 Contents 42 Research in India: Tomorrow and Beyond India has been a popular destination for clinical trials and, as there is an increasing acceptance of Indian data, Viraj Rajadhyaksha stresses that there is a need to ensure science and operational excellence remain top priorities. PAEDIATRICS: CLINICAL DEVELOPMENT & REGULATORY UPDATE 46 In Search of Safe and Effective Medicines Paolo Tomasi at the European Medicines Agency points out that, despite the controversy that still remains regarding the use of children as subjects of scientific studies, significant regulatory changes can make research safer and lead to wider availability of medicines for children. Paediatric Pioneers 52 The challenges of developing drugs for rare diseases are well recognised but as pertinent as ever; Karen Aiach of Alliance SANFILIPPO highlights recent progress for Sanfilippo syndrome an orphan disease affecting only one in 700,000 children. 56 PIP: Lab Perspectives Both regulatory authorities and pharmaceutical manufacturers agree on the need for running paediatric studies to reduce the off-label use of drugs in children. Katja Neuer-Etscheidt and Hermann Schulz at INTERLAB discuss how using a centralised laboratory can help to streamline this process. DRUG DISCOVERY, DELIVERY & THERAPEUTICS 62 Diabetes: Making Strategic Partnerships Rickey Reinhardt of Covance explains the need for pharma and biotech companies to partner with CROs to develop an integrated drug development strategy as a way of bringing more efficient combination therapies with better side effect profiles to market. In Search of Innovation 64 TQT trials are now required in the regulatory process in many countries, according to the ICH s E14 guidance. Alan Copa of Cetero Research reveals some approaches that can be used to improve the accuracy of TQT trial data, while keeping costs under control. 68 In the Heart of Russia In 2009, cardiology represented the fourth largest area of clinical research in Russia and the region ranked 11th internationally in terms of pharmaceutical sales. Lyubov Semenova at Pharm-Olam makes a case for Russia as a leader in global cardiology research. DATA MANAGEMENT & IT SOLUTIONS 72 Flexible LIMS The implementation of a modern clinical trial LIMS provides many benefits to the clinical development process by allowing quick identification and resolution of queries which helps to increase the value for trial sponsors, reveals Edward Krasovec at STARLIMS. 4

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3 Data Management & IT Solutions Flexible LIMS Edward Krasovec at STARLIMS reviews ways in which modern LIMS software can help CRO central laboratories to reduce costs and improve responsiveness when it comes to query resolutions The evolution of healthcare towards personalised medicine has resulted in growing numbers of studies targeting smaller populations with very specific disease states. CROs are finding themselves with more studies to manage and ever-increasing pressure to reduce both costs and development cycle times. Increasingly, these CROs are requiring flexible informatics solutions that allow the rapid implementation of business process change, help minimise the number of quality issues raised and streamline the resolution of queries. With laboratories playing a vital role in the majority of clinical trials, laboratory information management systems (LIMS) are a crucial component of the clinical trials informatics landscape. A flexible clinical trial LIMS lends CROs the required organisational agility to achieve its objectives. Any stakeholder in the clinical development process that relies on laboratory data, including CROs, pharma/biotech company sponsors and academic medical centres, should look for the following characteristics in a LIMS solution: Web-based system with multiple-tier architecture Intuitive user-driven configuration options Integrated study management, kit and materials inventory management, biorepository, and SDMS functionality RIGHT FIRST TIME A critical part of process improvement in clinical trials is the ability to get it right the first time. This means avoiding or minimising costly and time-consuming queries and exceptions. A good clinical trial LIMS will provide the tools that help a CRO achieve the desired process improvements throughout the clinical trial life cycle. By closely tracking inventory levels of kits and other supplies with integrated inventory management tools, the LIMS can allow operations personnel to optimise the use of existing inventory, transfer specimen collection supplies between sites, or provide suitable handling alternatives to avoid the multitude of issues that arise from samples being collected and shipped using the wrong containers and materials. next destination (either storage or testing laboratory) of the specimen. This will help ensure that the specimen is stored under the appropriate conditions and transferred to the correct laboratory location at the right time, therefore allowing timely testing of the specimen before viability expires. Furthermore, the LIMS should include integrated biorepository capability that manages consent status, tracks genealogy and maintains a complete chain of custody record for each specimen from accessioning through testing, storage, aliquoting, shipment and disposal. With configurable query User dashboards with key performance indicators, alerts and reminders Data analysis and reporting tools Powerful data export and interoperability tools With the cost of obtaining a valid clinical trial specimen ranging from $100 to over $2,000, effective specimen management is essential. The LIMS should give appropriate direction, based on the specific clinical protocol, to sample receiving/ accessioning personnel as to the 72

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5 Figure 1: LIMS closed loop tracking of specimen shipments Figure 2: LIMS provides alerts to issues requiring follow-up action templates, the biorepository should enable researchers to search the system for specimens that will help drive future scientific investigations. A web-based clinical trial LIMS gives investigator sites access to the system via a web browser allowing preaccessioning of the specimen using trialand visit-specific electronic requisition screens. Investigator site personnel can therefore electronically document the requisition data immediately after collection of the samples. Electronic requisition screens can include validation logic that immediately alerts data entry personnel to inspect data; therefore reducing data entry inconsistencies. For example, an absurd date of birth or a gender inconsistent with the last patient visit would be flagged at once. It is unlikely that all clinical trial sites would be willing to utilise this capability but consider the benefits if even a few highvolume clinical investigator sites were to use the pre-accessioning capability. Under this scenario, the accessioning process at the central laboratory would be streamlined significantly, with the focus shifted from data entry to simple documentation of specimen receipt and condition, and the validation of requisition data. By providing electronic access to personnel at the clinical trial investigator site, many queries can be avoided, and those that do occur can be identified and quickly resolved. Furthermore, the investigator s LIMS functionality can include a simple tool to document outgoing shipments by linking the kit IDs in the shipment to the courier airway bill number. This can greatly improve the central laboratory s visibility and awareness of incoming specimen load. It also provides traceability for any quality issues that may arise during shipment and handling. By making this link at the time of shipment from the investigator site, and using a web services interface between the clinical trial LIMS and the courier tracking systems, it is possible to implement real-time closed loop status and tracking of incoming specimen shipments (see Figure 1). QUERY RESOLUTION & IDENTIFICATION Even with the best run clinical trials process, queries and deviations may arise, often due to factors outside the CROs control. A well-implemented clinical trial LIMS will help CROs to manage such exceptions, by identifying the issues in a timely manner and allowing preventative action to be taken as soon as possible. The result is minimal impact in terms of both time and cost. As the trial specimens go through the workflows related to collection, shipping, and laboratory testing and reporting, the LIMS should automate the task of identifying deviations between the requirements specified in the clinical study manager and actual conditions. Furthermore, the LIMS should include a query management tool so that items can be tracked, managed and assigned, until each deviation is resolved. In order to give the operations personnel a fighting chance of successfully managing the clinical trial, they need immediate awareness of any potential issue that might impact on data quality or compliance with the protocol. The ability to act and react in a timely manner is crucial. Every potential query (issue) that may have an effect on the validity, availability or quality of the data generated through the laboratory must be identified, investigated and resolved as a matter of extreme urgency. For example, the sooner a call is placed to the clinical site, the greater the likelihood that the clinical site will be able to locate a missing sample and ship it before the sample stability period expires. Efforts to address inconsistent or missing data are much more likely to be successful if the follow up effort is initiated immediately after the original data collection and recording. As time passes, the chances increase that the relevant clinical site personnel will be unavailable, or unable to remember important information. Furthermore, prompt feedback to the clinical sites regarding recurring patterns of issues can be an effective tool driving continuous improvement in order to eliminate queries at their root cause. The clinical trial LIMS should include comprehensive data analysis and reporting tools to enable the CRO to provide this prompt feedback to the clinical sites (see Figure 2). IMPLEMENTING CHANGE: LIMS & THE AGILE CLINICAL TRIAL Clinical trial operations personnel are faced with a dynamic, demanding and competitive environment. Study amendments, new regulations, new cost structures and unplanned disruptions to operations lead to great operational challenges that have to be met in a timely 74

6 manner. The clinical trial LIMS should provide flexibility to enable rapid implementation of new or amended studies and business process changes in response to changing business conditions, and it must be possible to do this easily and with minimal disruption. It is also important that the changes can be implemented by the person or people responsible for the clinical trial without having to call on outside IT or supplier resources. The following are examples of how a LIMS can help CROs achieve the agile clinical trial they are looking for. The LIMS must enable a CRO to quickly set up and validate a new or modified study. Any modification that changes the testing, kit requirements, accessioning, specimen handling, reporting workflow or business rules must be appropriately reflected in the configuration of the study in the LIMS. A modern clinical trial LIMS will utilise a data-driven configuration approach to allow changes in the study to be implemented using configuration wizards within the various applications or via general system configuration tools. A multi-tier architecture that separates configuration tools and application modules from underlying technology and core software code enables these study changes to be implemented without needing to change the underlying software code. A web-based LIMS can be easily deployed to a new facility when increased shipping costs, regulatory restrictions or increased workload make it desirable to start up a new laboratory or sample handling facility. Web-based LIMS technologies greatly reduce the infrastructure costs and allow access to any data from any location, employing intuitive user interfaces that reduce complexity, training costs and time. Also, a user-configurable clinical trial LIMS enables specimens to be easily redirected to a back-up laboratory (including third-party outsourcing laboratories) in the event of a laboratory or instrument breakdown. A clinical trial LIMS that includes an integrated scientific data management system (SDMS) can also be utilised to streamline the implementation and data entry related to the use of a partner reference laboratory. The SDMS can parse unstructured reports (in Adobe PDF, Microsoft Word or other formats) produced by external laboratories, store the test results and related information into the LIMS database, and make the key data available across the organisation from within the LIMS. SDMS has lowered the barriers to implementing these interfaces by including artificial intelligence capabilities that greatly simplify the parsing of an external laboratory s report file. Electronic acquisition of this external lab data reduces error-prone manual data entry, saves time, and provides more immediate data visibility and value to all stakeholders in the clinical trial. DOCUMENT & FILE MANAGEMENT Clinical trial operations personnel have a multitude of documents and files that must be managed, including scanned requisition forms, laboratory services agreements, FDA 1572 forms, SOPs, as well as a variety of technical reference documents, manufacturers monographs and scientific articles. Managing these electronic documents and files can become a major overhead for the CRO and add to the complexity of managing the trial itself. A clinical trial LIMS with an integrated SDMS as well as streamlining data entry from partner reference laboratories can provide a secure storage repository and the means of managing these documents and files. The files can also be linked to the appropriate data objects, including the clinical trial itself or a specific clinical trial accession or site. The SDMS can offer powerful content acquisition capabilities that use unique artificial intelligence algorithms to process unstructured data from documents in an automated manner. Documents can be routed to a workflow, either automatically or manually, by attaching a document to a specific workflow ID. The SDMS can extract content from the document and, as part of a configurable workflow, automatically create the appropriate data within the database. About the author Edward Krasovec is Senior Manager, Global Marketing/ Product Development Clinical at STARLIMS Corporation, an Abbott Company. He oversees business development and product management for clinical laboratory information management applications, including clinical trials, biospecimen management and healthcare. He has nearly 20 years of management and technical experience with DuPont specialising in laboratory management, business planning, research and operations. Ed holds a BSc in Chemical Engineering from Penn State University, PA, US and an MBA from Drexel University, PA, US. ed.krasovec@starlims.com With this capability it is then possible to parse a clinical protocol or data management agreement document and automate the data entry related to building a new clinical trial record consider the operational efficiency advantages of using such a smart protocol document to auto load clinical trial definition parameters into the LIMS. CONCLUSION The implementation of a powerful and modern clinical trial LIMS provides many immediate benefits to CROs and other stakeholders in the clinical development process. The LIMS can drive a get it right the first time approach and improve the ability to quickly implement changes driven by the trial sponsor or other external factors. By doing this, the CRO central laboratory can reduce clinical development costs and deliver increased value to their customers. 75