Investigators engaged in drug or device discovery and development increasingly regard imaging modalities as technology to improve efficiencies, make faster go/no go decisions and reduce time-to-market. Beyond classic laboratory tests, medical images are raw datasets that empower the industry to improve imaging software or re-visit previous clinical trials with new technologies in efforts to discover new information. The digital revolution that began in the 1990s with the emergence of the Internet ultimately resulted in the digitalization of medical imaging systems. This made objective quantification of morphological and functional parameters feasible — not only enhancing diagnostic quality, but also paving the way to incorporate imaging technology as a tool in clinical trials. Concurrent and continuous advances in imaging technology have firmly established imaging devices in the clinical testing armamentarium of centers engaged in clinical trials. Accordingly, usage of imaging biomarkers in clinical trials today is growing at an accelerating pace. Perceptions of imaging technology are changing — imaging is increasingly viewed as one of the most powerful cost-savings strategies to measure and monitor the effects of the drug or device under evaluation. Imaging’s Growing Role in Clinical Validation As a result of the digitalization and technological refinement of imaging systems, imaging’s role in clinical trials has grown tremendously over the last five years. Increasingly, university-based research groups, contract research organizations specializing in imaging (i.e., imaging core laboratories), data management firms, laboratory service providers, drug companies and device manufacturers are using medical imaging technology to improve both the efficiency and accuracy of medical product evaluation, and to decrease the time and costs involved in successfully bringing new products to market. A report from Mass Insight Corporation’s Collaborative Biomarker Committee (CIBC) stated that imaging will have three primary benefits in drug development: improved selection of trial candidates, shortened trials and accelerated regulatory approval. The report maintains that imaging and biomarkers will continue to play key roles in proving efficacy, assessing response to therapy, earlier disease detection, drug delivery tracking, pharmacokinetics and dosing, toxicity, distinguishing between responders and non-responders, and providing surrogate endpoints for drug approval. Imaging and Advanced Information Technology Researchers are establishing clinical trials that cover larger demographics and include record numbers of subjects. This implies more international studies and more sites to coordinate for a given trial. To address this growing trend, the Internet has become a powerful conduit for remote sites and remote readers to coordinate with a central facility. Given the industry-wide shortage of radiologists, web-deployable imaging applications and dynamic workflow management tools provide technology to connect and centralize administration, reading, quality control, image management and image distribution. This is critical for facilitating multi-center trials, in which data and data review resources are widely disseminated. Critical Path Emphasizes Greater Reliance on Imaging In 2004, FDA validated imaging’s importance in clinical trials by announcing the Critical Path Initiative. This project is FDA’s attempt to encourage and facilitate a national effort to modernize the scientific process that culminates in the development of a potential human drug, biological product or medical device. Since then, FDA has joined the National Cancer Institutes (NCI), the pharmaceutical industry and academia in several activities that will create the first standards for medical imaging’s use in the development of new drugs and devices. These activities are geared toward validating new imaging technology and advocating this technology’s use when appropriate to advance clinical research and clinical trials. An initial product of the critical path initiative was FDA’s report titled “Guidance for Industry, Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics," released in April 2005. This document positioned two tumor assessments as desired endpoints: objective response rate (ORR) and progression-free survival (PFS). Both of these endpoints are based on radiological imaging technology. Increased Pressure to Reduce Costs I Trials for drug and device development have been vulnerable to failures, slowdowns and barriers, making the reduction of both the number and cost of failed projects a major imperative in the pharmaceutical and medical device industries. From 1993 to 2003, R&D spending by both the pharmaceutical industry and federal government increased by 270%. During that same time, the number of new submissions to the FDA has consistently declined. Mass Insight’s CIBC noted in 2006 that “biomedical imaging is widely viewed as one of the most promising tools to improve the process of drug development and reduce the costs of failure." Remaining Obstacles Prevent Optimal Use of Imaging I Despite the complete digitalization of three major clinical trial modalities — CT, PET and MR — and significant technical advancements, challenges persist for centers that use digital imaging in clinical trials. The difficulties lie in either inefficient or dated in-house solutions, as well as integration or general usage problems associated with employing multiple third-party systems. These challenges present obstacles when groups work toward building an integrated and accessible image repository. Additionally, utilization of numerous image viewers — coupled with connectivity and workflow issues — cause significant inefficiencies. Regulatory compliance also presents a significant resource effort for most centers. Repository I Multi-slice CT, 3D MRI and pathology data sets are some of the largest image files ever acquired; each file can be in the several gigbyte range. In fact, compressed pathology images typically range in size from 1-2 GB. Standard hospital-based archive solutions are ill-equipped to handle image files of this size and are unable to store all metadata DICOM, non-DICOM, HIS/RIS and text data. Furthermore, clinical trials place major demands on repository bandwidth; consider the prospect of radiologists at 1,000 participating sites simultaneously uploading relevant image sets. Clinical trial sponsors, as well as service providers, also retain image data for a range of periods, anticipating the application of potential future segmentation tools or algorithms to these archived images in efforts to find new uses for established drugs. Such broad storage requirements and general access and security concerns can make organizing and warehousing the repository a real issue. Viewer I Most viewers used in the clinical workspace are capable of showing images from a single modality only, which has made neurology clinical trials — which use MR, CT and PET images — less than optimal. Additionally, in multi-center trials, viewing problems often arise when participants with different acquisition devices attempt to share images. Furthermore, numerous useful clinical trial tools or specific algorithms sometimes developed through third-party partnerships are not accommodated on typical off-the-shelf viewers, including trial-specific user roles or audit trail requirements. Standard industry workstation viewers are incapable of reading images over the Internet, eliminating the possibility of dispersed viewing stations. Finally, clinical trial participants often unknowingly employ freeware viewers that can sometimes make general assumptions on missing standard DICOM tags, thus potentially producing unsubstantiated calculations. Connectivity I The ability to rapidly and easily disseminate voluminous amounts of image and text data within and between centers is the lifeblood of a clinical trial, particularly multi-center trials that may involve hundreds of physicians based at global sites. Clinical trial sites that rely on non-standard image and workflow management configurations create “islands of information" that result in bottlenecks in data delivery and delayed data access that interrupt workflow between internal and external users. For example, a trial sponsor and the imaging core lab it contracts with may be operating from separate databases that don’t share a communications link, preventing real-time data access. More traditional methods of image delivery — express mailing CDs or shipping hard drives, for instance — risk loss and damage en route. In addition, in the absence of connectivity, sites must generate large amounts of paper records that also complicate and slow down workflow and make creating an audit trail for regulatory compliance particularly complex. Workflow While in one sense the incorporation of digital imaging systems into the clinical trial matrix substantially improves workflow, it also creates significant new time costs in radiologist image interpretation. Even seemingly minor components of overall workflow, such as discrete keystrokes and mouse clicks, can exert a serious financial impact when multiplied over the vast number of studies and the duration of a clinical trial. Study coordinators realize that shaving even a few seconds off of a radiologist’s task list could result in cost-savings of tens of thousands of dollars. In addition, in a clinical trial setting, study data may be flowing in from several different modalities and various vendor systems. Clinicians often find themselves expending time moving to and from several different workstations. The inflexibility of the standard workstation is a significant drag on clinical trial workflow. Regulatory Compliance Managing regulatory requirements is complex if the clinical trial participant uses a non-digital workflow. Not only are these centers required to log even the most minor image manipulations and include all metadata, but they also must create, maintain and disseminate a paper-based audit trail for trial sponsors and FDA. Regulatory compliance in this scenario is time-consuming and vulnerable to human error. Conclusion The growing incorporation of digital imaging in clinical trials of devices and drugs marks a major shift in how sponsors use technology to reduce costs for clinical trials. Recent high-profile successes that used imaging modalities as biomarkers or clinical endpoints have validated this new paradigm, as has FDA’s official advocacy of medical imaging in the development of new drugs and devices. However, clinical trial participants have experienced growing pains related to in-house efforts to create optimal solutions for viewer, connectivity, workflow and regulatory compliance. Merge Healthcare offers a new way to analyze and manage imaging in clinical trials through a unified platform to optimize these critical components of the clinical trial’s imaging toolset. n As a result of the digitalization and technological refinement of imaging systems, imaging’s role in clinical trials has grown tremendously over the last five years. Jon DeVries President, Merge Healthcare’s eclinical division Merge Healthcare Innovating Imaging in Clinical Trials MERGE Healthcare is a leading health IT solutions provider, with over 20 years of experience in medical imaging and technology, directly addresses the imaging challenges that clinical trial participants face. For more information, visit merge.com/eclinical.

Download PDF