The increasing amounts of clinical data needed for drug approvals have companies exploring creative solutions.

Patrick McGee
Senior Editor

Pharmaceutical and biotechnology companies are in the business of discovering, developing, and producing drugs and biologics using the latest technologies, but when it comes to managing reams of clinical trial data, they can sometimes resemble a large, lumbering bureaucracy. That shortcoming was manageable when regulatory hurdles were lower. Now, the demand for more data on drug safety and efficacy means larger clinical trials that yield more information than ever before, but which obviously require more and more money and people. Companies responded with a combination of outsourcing, information technology tools, and partnerships geared toward increasing efficiency.

"Data management for the industry has become an enormous task. If you think of the growth in the number of studies that are needed to get a submission these days, and if you think of the tremendous growth in the number of patients associated with those studies and the number of sites, it's not hard to see that the amount of data has grown almost geometrically over the last 10 years," says Ira Spector, vice president of clinical development operations and vice chief of operations at Wyeth Research, Monmouth Junction, N.J. "All of that data has to be analyzed and effectively collected, cleaned, and analyzed, so it's a huge task."

Spector says when Wyeth considered the increased demands, the company realized that many of the older data management techniques were not adequate. "We took a

click the image to enlarge  Clinical workloads have increased at many companies. Wyeth had 12 new products, excluding vaccines, entering phase I each year and experienced a 50% increase in hard copy case report form pages in 2004. (Source: Wyeth Research)

strategic look at the data management requirements where we were and where we thought the trends were going several years ago, and we realized that the IT [information technology] infrastructure related to that was growing at a very high rate and was going to require significant investment." For example, studies that used to be done with simple databases such as Microsoft Excel are no longer permitted because they are not compliant with the US Code of Federal Regulations (CFR) title 21 CFR Part 11, which provides guidance on electronic records and signatures for the food and drug industry. "There's been a huge trend toward greater complexity, huge volumes, higher standards, and basically an entire IT subindustry has grown up around this," Spector says.

One company in that subindustry was Integic Corp., which provides the electronic medical records for the US military's health services and is the developer of Global Trials Manager (GTM), a software system that manages the pharmaceutical clinical trials process. In March 2005, Integic was purchased by Northrop Grumman Corp. and folded into its IT group headquartered in McLean, Va. Companies are clearly interested in getting clean data as quickly as possible. That resulted in big demand over the years for electronic data capture (EDC) products, which have had mixed results, says Jane Light, clinical trials process engineer and product manager for GTM.

While adopting EDC can provide many benefits for companies, using the process is basically "paving the cow path," she says. "It's taking a process that's already out there and maybe making it go a little faster, but it's not necessarily making it that much better. I think that real jumps in this industry are going to occur when you can extract information from the source data and not put an artificial process over it. But I think that's still quite a ways out. I think that having the tools and the infrastructure and the regulatory issues for that are going to take a long time."

While vendors like Northrop Grumman have been thinking of ways to meet the data management needs of their clients, pharmaceutical companies like Wyeth have been forced to rethink what their focus should be, says Spector. Data is the primary product used to formulate new drug submissions, so the IT budgets of major companies became a significant component of the business in order to manage the data.

IT infrastructure
"The IT infrastructure is a critical component of how you develop drugs, because once you frame the question at the front end, the terms of the hypotheses and the protocols that you've designed, from there to where you're interpreting the data and writing up your analyses, everything else underneath that or in between that is about collecting data, cleaning data, analyzing data. So the IT systems that you use to support that really are the critical piece." Companies have the option of going it alone, which very few are still doing, or using contract research organizations (CROs) or other arrangements.

In 2000, Wyeth turned to management consulting, technology, and outsourcing firm Accenture, New York, to help them retool their research and development organization.

click the image to enlarge  Among other features, the Global Trials Manager software system can generate progress metrics graphs that allow researchers to run more efficient clinical trials. (Source: Northrop Grumman Corp.)

In the first year, they helped Wyeth almost quadruple the number of molecules coming out of discovery from three or four a year to 12; over the last five years, Wyeth discovered 60 molecules, says David Boath, a partner in health and life sciences at Accenture.

They were also able to help Wyeth reduce the cycle times of phase I studies by 65%, but that success was not without a downside, says Boath. "If we have the same way of doing clinical data management that we have elsewhere, then we're just not going to be able to process all of these molecules, so we needed a new way of thinking about this. It was getting to a stage where we wanted to prosecute all these molecules through phase III, and we needed a dramatically different cost structure and productivity model."

They responded to that quandary by forming the Alliance for Clinical Excellence (ACE), a separate entity created by Accenture to manage Wyeth's data, says John Shelton, assistant vice president of global clinical data management at Wyeth. For ACE, about 200 people from Wyeth joined Accenture and now work in centers in the United States, Europe, and other parts of the world. "We transferred a lot of knowledge and capability and relied on Accenture's ability to build the entry and validation capacity in Bangalore, which they have done." There are 400 employees in Bangalore, India, who handle data entry and editing. "We were either faced with the choice of making a significant internal investment in upgrading capability," says Shelton, "or finding another way of doing it. What we saw in Accenture was the ability to manage IT and transactional processing."

In 2002, Wyeth was outsourcing 60 to 65% of their data entry and validation, but after the establishment of ACE and the opening of the Bangalore site, they gradually shifted away from their CRO partners. By the end of 2005, they were down to one CRO supporting one study in clinical research and development, Shelton says. Boath says another goal of the partnership is to reduce Wyeth's cycle times by 75% and cost structure by 35 to 40%. Shelton says Wyeth is very happy with how the venture has gone, and it drew the interest of others. Boath says Accenture is working with several large and small pharmaceutical and biotechnology companies on a variety of projects.

Clinical trials software
Although arrangements such as this are attractive, many companies will also choose to use tools such as Northrop Grumman's GTM, which features an integrated planning and monitoring environment that simulates all aspects of a clinical trial. It supports research study start-up activities, site initiation, patient enrollment and monitoring, data collection throughout the trial, and analysis of project metrics and results. Other features include real-time reporting and tracking, automated alerts and notifications of tasks, and the ability to search for, identify, and respond to key data points.

Light says GTM is easy to bring online and begin using. "It's not something where you have to go in and build your business process into it and all your terminology. The application comes ready to be able to use interfaces to put in all of that information, and it will ripple through the rest of the system seamlessly." She says another differentiating factor is how it handles offline processing. When companies send personnel to monitor a clinical investigative site, they don't always have an Internet connection and they often don't have much room to work in. "Being able to use information and process it offline, again without having to put it on paper and give it to someone else to enter into the system, would be a key capability."

To do this, the GTM uses Microsoft Office's InfoPath, a program written in Extensible Markup Language (XML) that allows businesses to design and fill out electronic forms that can be easily shared and manipulated. "You don't need to have any type of Internet connection, but through XML we transfer information to and from the database with reconciliation rules, which again, from the user perspective, is something they don't need to know anything about. It just happens when they download things to get ready to go out to the site and when they plug back in at the end of the night," Light says.

Integic began developing the GTM in 2003 with Icon Clinical Research, a CRO in Dublin, Ireland, that manages phase I through phase IV clinical research studies for the pharmaceutical, biotechnology, and device industries. Icon Clinical Research validated the GTM, and it was put on the market last June. "Icon concluded that no system existed that delivered the functionality and flexibility to meet customer needs. We therefore decided to enter into a joint development project with Northrop Grumman, leveraging their technical skill and industry knowledge with Icon's core competency in managing clinical trials. Also, we saw future advantages in integrating GTM with our existing Northrop Grumman CRF Work Manager system, which enables the workflow of our data-management process," says Michael McGrath, Icon's vice president of global information technology. He says that GTM has had a very positive impact due to its flexibility, up-to-the-minute reporting combined with real-time critical document tracking, cross-study metric reporting, and remote monitoring capability.

Although the GTM only came on the market a year ago, Light says Northrop Grumman is already considering other features, including a budgeting and payments module, clinical supplies tracking, and integration with document-management systems and other project-management systems. "Our strategy has always been to make integration easy. One of the strengths of the original Integic was building products that easily integrated with other systems, and we will look at doing that with GTM in the form of services and open integration points," Light says. "As in most industries data comes from a lot of different sources, and the better that you can manage that in an integrated environment, the better off you are."