Trial Planning: Drug Development's Unsung Hero

By Ed Seguine

May 26, 2009 | Clinical trials are incredibly complex and costly endeavors—in fact, clinical research and development is arguably the most inefficient industrial activity in the world. The process requires selecting from literally thousands of compounds to find and test the most promising few in thousands of people that have specific conditions, across hundreds of sites, worldwide—all under the most exacting conditions and staggering costs. Indeed, this is a heroic endeavor.

In the past, pharmaceutical research and development (R&D) spending was somewhat insulated from periodic economic slowdowns, but that is no longer the case as headlines announcing mega-mergers and mass-layoffs affecting R&D are becoming common occurrences. Now, more than ever, clinical trial sponsors and researchers need to use technology to make their core processes more informative, efficient and cost-effective.

Success in Other Industries
Generally speaking, the pharmaceutical industry has lagged far behind other sectors in leveraging technology to streamline core processes, but the complexities of today's environment require that pharmaceutical companies adopt a more disciplined and comprehensive technology strategy that is aligned with the entire clinical development process. While the industry is in the midst of a stampede toward enterprise adoption of electronic data capture (EDC) technology as a way to achieve process efficiencies, EDC is just one piece of the puzzle. The only way to achieve lasting productivity gains is to apply lessons learned from other process-intensive industries—notably manufacturing, but to a lesser degree, construction and retail as well.

Each of these industries identified their business processes as a system of interdependent, often time-delayed events with various feedback loops, and deployed technology to optimize performance across the enterprise rather than simply improving discrete activities. For example, look at Dell's integrated approach to manufacturing user-configured computers. Or, a major Las Vegas hotel construction project with computerized blueprints that provide detailed resource and timeline forecasts. Or, Wal-Mart’s retail empire managing inventories that rely on past data and current sales performance.

These industries have achieved astonishing transformations by applying two key principles: 1) Implement technology at the early planning stages of core business processes and 2) Architect a data feedback cycle to supply those planning tools with meaningful information—preferably real-time. The same principles should be applied to help pharmaceutical companies improve clinical trial planning and development.

Clinical Development Today
Within the pharmaceutical industry, trial planning—and specifically protocol design—has traditionally been viewed as an art rather than a discipline. Generally speaking, study designer or protocol authors painstakingly focus on the scientific details of each individual trial with very little understanding of the operational impact of their decisions. Typically, at this point in the process, the only technologies being applied are Microsoft Word to access approved templates, a regulatory repository such as Documentum to store documents, and e-mail to solicit comments from colleagues and potential investigators. 

Only later in the clinical trial process does technology really come into play—most notably with EDC—and, in some cases, more than 100 separate systems are involved in the executing, analyzing, and submitting of clinical trial data. Unfortunately, most of these systems have their own data structures and few can work together, or even work at all, without substantial manual intervention. Almost all represent solutions to very specific problems—site selection, investigator contracting, lab management, statistical analysis, etc.—but generally contribute little to optimize the overall process. The technology landscape in clinical development thus fails to deliver the transformative effect that sponsors desperately seek because the solutions are not deployed early enough in the business process and don't make use of available data from the start. 

Benefits of Early Planning
Electronic protocol solutions offer the greatest potential for comprehensively addressing the complexities and dependencies of the entire clinical development process. The ideal e-protocol solution simultaneously captures critical study design information both as a document and as data. With the study protocol reflected as data, similar to a computerized blueprint of a hotel under construction, there is a single source of the "truth" about the study, before it even begins.

Consequently, the business processes that are dependent on that data (which were previously "locked" within the document and had to be manually input in multiple single-purpose systems) can now leverage technology as part of a unified system to do things that have never previously been possible. Multiple benefits accrue from this early planning:
• EDC database setup and CRF development times are reduced—the information from the protocol schedule of events specifies the data requirements for the study;
• Data collection variables can be analyzed in conjunction with the statistical plan to identify missing and unnecessary variables before the study begins;
• Rationale and relevancy of data variables can be propagated to downstream systems—e.g. the EDC system recognizes which data queries relate to variables associated with the primary objective and require greater validation focus through the use of edit checks or query resolution; and
• Study designs can be critiqued by applying rules to the data specification to identify inconsistencies or extraneous details that could lead to amendments.

Benefits of Data Modeling
Perhaps the most transformative effects of early trial planning are the ability to gain insights that were not previously possible, or to do those activities with the precise understanding of the operational impact of changes to the study design. These types of activities rely on the availability of data collected in previous studies to inform decisions about current studies—the key being the ability to model the impact at the time the study is being designed in the first place. Again, the benefits are significant:
• Protocol feasibility can be performed by comparing defined inclusion/exclusion criteria to existing databases to determine the availability of patients meeting the criteria;
• Budgeting and resource estimations can be made based on key trial parameters and previous cost/performance metrics; and
• Clinical supplies can be forecast based on the study requirements and expected recruitment projections.

Heroic Efforts Ahead
To date, the pharmaceutical industry has largely focused on deploying technology at the trial execution stage, where the applications are more mature and the business need has generally been widely acknowledged. Early planning applications have generally focused on utilizing data to identify potential sites or patient populations; their adoption has also been hampered by the inability to have a precise specification of the protocol available in time to do the manual work necessary to model the outcomes. 

With the relatively recent availability of eProtocol tools (within the last 24 months), a number of major pharmas have experimented with various in-house applications and the few commercially available tools. The feedback to date has been "mixed" as early adopters struggle to quantify the immediate benefits of an integrated planning/execution systems view of clinical development when most of the related systems don't work together either. That's not surprising at the early stages of technology adoption and the most recent experiences have shown great potential to reduce CRF build times by up to 40 percent.

Clinical research is indeed a heroic endeavor—everyone from the healthy volunteers who willingly participate , to the patients with hopeful expectations of finding a cure, the physicians who care for them and the researchers developing new therapies. These are the true unsung heroes in clinical development—but it will take a different brand of hero to champion the adoption of a more disciplined and systematic approach to clinical development—starting with study design—to achieve the transformation the industry claims to be seeking.