The economic consequences of inefficient work processes in clinical trials are significant. The average daily cost of drug development runs about $30,000 per day and rises by 10% to 12% per year. Development cycle times range from three to 12 years.1 In typical operational practice, the line management of a competitive firm strives to achieve the highest volume of successful new drug application (NDA) submissions (effectiveness) in the shortest practical time (efficiency). This combination reflects the business throughput of an organization.
"In all affairs it's a healthy thing now and then to hang a question mark on the things you have long taken for granted."-Bertrand Russell
The economic consequences of inefficient work processes in clinical trials are significant. The average daily cost of drug development runs about $30,000 per day and rises by 10% to 12% per year. Development cycle times range from three to 12 years.1 In typical operational practice, the line management of a competitive firm strives to achieve the highest volume of successful new drug application (NDA) submissions (effectiveness) in the shortest practical time (efficiency). This combination reflects the business throughput of an organization. Unfortunately, the usual methods of management and reporting seem to reach their methodological limits early and invariably slow throughput because of various obstacles:
The focus of management conversation around the cost of drug development has been moving gradually from efficiency to effectiveness. These factors can be distinguished by the relationship of process to outcome:
If effective business throughput is the key to the ongoing health of a pharmaceutical organization, then the strategic priority is determining the actions to support this. Numerous contract-based tactics are available such as arrangements with contract research organizations (CROs) or site management organizations (SMOs). A strategic move that has a significant impact on a firm's long-term competitiveness and prosperity is that of pushing processes further outside the boundaries of the organization. This has long been a mainstay concept of traditional quality methods. The orchestration and integration of the processes between internal and external organizations is both a collaborative effort and a hurdle that many quality programs overcome with carefully designed procedures and standards for interaction. Many drug development operations follow this thinking by prescribing rigorous standard operating procedures (SOPs) as the standard of interaction. However, uniformity of procedure is really less important than predictability of positive outcome.
One promising theoretical model is the Virtual Research Organization (VRO). Although many companies are looking into this approach, at this point in time, most companies have chosen to keep data concerning implementation confidential. Despite the fact that early evolutionary instances of this approach are visible in the relationships between pharmaceutical companies and CROs, progress toward strong collaboration is slow. Therefore, much of this discussion is theoretical. This paper examines this theoretical model in survey form and proposes some additional clarifying elements and approaches.
Figure 1. VRO architecture.
The structural essence of the VRO model is drawn from traditional quality theory. In this model, the importance of reducing and managing variance is linked to the relationship between companies and their suppliers. Most effective quality management scenarios begin by attempting to control variability in the environment. Exposing and managing processes is a first step toward reducing variance. Understanding the influence of uncontrolled factors on variability is a consequence of examining processes. Intersecting departments, divisions, or suppliers can reduce predictability if they do not rigorously participate in the local quality culture.
Many companies with evolved quality management programs view suppliers as an integrated business element. In other words, the relationship is not merely a matter of efficient ordering and order fulfillment based on simple contractual parameters. Rather, a limited number of key suppliers become partners involved in the realities of manufacturing and product delivery. In some cases, a supplier will actually maintain an office or on-site staff within a client organization. The permutations of this model can range from straightforward supply of technical products-computing technology to surgical adhesives-to services such as management or clinical consulting.
Just as manufactured items often depend on parts from various suppliers, work process functions depend on information from numerous sources. The VRO, therefore, takes the quality management approach and develops it using process and information as the basis of interdependence. For example, within a clinical trial, data is constantly changing along the work process map. It is critical to effective trial management to be able to communicate and fill informational gaps. One of the first steps in developing an optimal process map within the VRO is developing a clear understanding of the path between the necessary sources of data. Organizational intersections are more easily established with a clear high-level map of the process with data feeds identified. Modern competitive pressures often cause organizations to succumb to the practice of sniping at defects rather than effectively eliminating their root causes. In the constitution of a VRO, what is especially important is the real-time visibility of relevant and appropriate data across the virtual organization-not just as a disclosure in intermittent reports.
According to the Gartner Group, "process logic consistency, flexibility and accountability will be prime reasons for deploying workflow-enabled e-health applications."
Workflow process management in a shared virtual environment requires a new operational approach for controlling and understanding the clinical process. Once the evident structure of the VRO has been described, the organizations involved must establish it as an operation to achieve a more effective clinical trial process. However, this goes beyond addressing technical complexity. Organizations must move toward higher levels of performance by reducing latency or delay within clinical study process. A more collaborative organizational app-roach with more consistent practices is a key element in reducing delay. The VRO is an organizational and technology model within which the work process map is designed less with consideration for organizational boundaries and more with the goal of achieving effective work process.
For example, a pharmaceutical company may contract data entry with a CRO, quality review to yet another CRO, and handle discrepancy processing internally. Although numerous organizations touch the work process, technology can provide a means to assign participants to work queues along the same map. By implementing a VRO using work process automation, allied but distinct organizations can be tied together allowing real-time access to information related to the clinical trial. Consequently, various groups can assume new roles in the clinical trial process to better address the unique requirements of each group as well as streamline the process itself (Figure 1). Several straightforward business benefits are possible:
Specifically, a VRO approach can provide a history and traceability of data from clinical sites to sponsors and expedite the internal review and release process.
Technology view. Each drug development project may have unique procedures and present many management hurdles that typically lie across organizational boundaries. Technology becomes the means of integrating the process map into the operation. By beginning with the trial as an end-to-end process, implementing work-process automation offers a competitive approach to managing activities throughout the clinical trial by breaking down some of the common hurdles in the clinical study process:3
Using technology, the traditional work- process structure and the organizational management can reflect the purposes of the VRO. A work-process automation server not only facilitates the business rule flow, it also coordinates the delivery of information along many common or possible delivery channels-scanned paper, faxed documentation, email delivery, wireless communication delivery, formatted file transmission, or XML-based CDISC structures. A typical example of work-process delivery is the automatic generation and transmission of an email message to an appropriate work group when an adverse event becomes evident. Another common use of a delivery mechanism is the automatic transmission of a message to a supervisor or project stakeholder if work remains in a process queue too long.
Integrating work-process automation, Internet technology, and emerging standards provides a powerful technical means to create a clinical dashboard that helps orchestrate the dissemination and movement of information to where it needs to be in the VRO. It presents data in an easy to use format regardless of the underlying technologies supplying the data. A quick display of daily work activities and work queues enables the data to be presented at the time it requires attention. This helps streamline the business process. The potential result means weeks of time savings to the clinical study. For example, a small four-hour delay moving work from one department to another, or from one person to another, needs to take place only 10 times during the study to result in a week's delay. Other slowdowns originate in well-intentioned but non-contributing efforts. Research has indicated that the longest running queries appear to deal with matters that have little impact on study conclusions.4 It becomes easy to see how these process inefficiencies can prolong a study.
The notion of a clinical dashboard in the VRO is more than just a front-end Web application that provides an extended view of a particular tool. It sits above the underlying technologies and processes, pulling together the data, providing a view of the total business process. By orienting key actions, decisions can be anticipated and made more quickly. Better information at the right time improves the effectiveness of interacting organizations and reduces guesswork or after-the-fact action. For example, not every area of clinical query is relevant to the study outcome, and extra time spent on certain kinds of queries can actually cause delay with no benefit. (Think of an example of concomitant medications where the data can be useful in the case of an adverse event, but don't usually have much effect on the overall outcome of the study.) Organizations are able to operate independently of their discrete functions and locations as if they were organized around the processes and with less inclination to reorganize or merge. By offering a large number of incremental improvements, the VRO model is able to improve the overall effectiveness of the resources associated with the trial. Actual results are typically measurable through data available within the work-process engine.
Two areas of emerging technology that will dramatically improve the leverage of the VRO are standards-XML (eXtensible Markup Language) and CDISC (Clinical Data Interchange Standards Consortium). They offer new technical currencies for moving data more quickly and authoritatively. Proposed CDISC data standards offer a consistent modeling approach for describing the data associated with clinical trials. The current CDISC Operational Data Model (ODM) takes into account numerous subtleties of vendor-independent clinical data exchange including key structures and consistency with submission requirements. The relationship of CDISC to XML will become more fully defined over time.
In the context of pharmaceutical industry data management, XML currently provides a reliable set of "wrapper" services to simplify the movement of data among applications or organizations. Of particular value in a VRO discussion is the ability to associate digital signature functions with the movement of information via XML. In this case, a VRO-specific XML schema would be deployed to contain data and other required process-related structures. This will ensure that data is moved through the process with integrity and authority (Figure 2). This means that as data is processed and as it travels from one organizational domain to another and back, its defined requirements for consistency and quality can be more practically maintained. Biometric technology is offering a superior integration opportunity for organizations to stamp their data authoritatively. Any biometric identifier that is used, however, must be acceptable according to several criteria-universal, consistent, unique, permanent, inimitable, collectible, tamper-resistant, and comparable.5 Additionally, the more authoritative nature of digitally signed data offers a stronger backbone to 21 CFR 11 requirements.
Figure 2. VRO data integration.
Pharmaceutical companies partner with CROs and other pharmaceutical support organizations (PSOs) to battle the increasing cost of the drug development cycle, and to help meet the growing needs of the drug development pipeline. According to the Tufts Center for the Study of Drug Development, pharmaceutical organizations will increasingly outsource to niche service providers despite increased regulatory and legislative attention to the clinical trials process and as full-service CROs continue to consolidate.
Senior management must still convert the competitive pressures of the market and the logical demands of the clinical trial process into a coherent strategy tailored to a more effective operation.
In developing a VRO strategy, the evaluation and strategic decision-making process will generally follow an identifiable path:7
The nature of the VRO requires that the upper management of multiple organizations acknowledge and act on their long-term mutual interests. An area of particular nuance (resolved through good governance) is the concept of "external environment." The VRO realizes some of the benefit of strategic decision-making by blurring the distinction between the external and internal environments. A powerful consequence is the significantly increased mutual business benefit and improved operational effectiveness of "focused factory" collaboration without the need to physically merge.
The VRO is an exercise in hanging a question mark on the process boundaries between organizations that have long been taken for granted. While not necessarily an ultimate solution to the effectiveness problem, the VRO does offer a means for better control over processes and information. Pharmaceutical companies will continue to focus on streamlining the clinical trial process. By focusing on minimizing the queuing problems associated with a work process and by addressing the inherent stop and start nature of data transfer between process tasks, clinical trial data is able to work more efficiently across organizational boundaries. The strongest return on a technology investment is realized when it magnifies an organization's strengths and business purpose. The VRO uses workflow automation and portal technology to focus clinical trial business processes and the movement of data to maximize the strategic value of technology investment.