A physician participating in a clinical study takes a patient’s blood pressure, height, weight and reactions to the trial treatment. The physician picks up a pen or pencil and enters the information onto a paper chart. Later, the information is transferred from that chart to a computer database that is not connected to the organization sponsoring the study. Is this 1980? No, it’s the year 2000.

Although the opportunities of technology have been knocking on the door of CRO industry for years, the clinical trials process remains a “throwback to the Stone Age,” rather than the high-speed information superhighway of the 21st century. The clinical trials process is still 85-90% paper based, a mind-boggling figure in an era characterized by digital and wireless communication, notebook computers and flat screen TVs. This situations begs a number of questions:

• Why is the clinical trials process stuck in “the old days?”

• What will it take to change it?

• How has it changed thus far?

Rick Nelson, senior director of clinical operations technology at PharmaNet, a CRO, commented, “The way clinical research is done hearkens back to the Stone Age, which is only a slight exaggeration. I can’t think of another industry that conducts business the same way it did 30 or 40 years ago. Some technology has been brought in to expedite a few of the processes, but in general, the whole collection, recording and correction of information is being done the old-fashioned way; with lots and lots of people. And people do tend to make mistakes. It’s not efficient, it’s prone to error and it’s crying out for application of technology to modernize the process.”

Steve George, vice president of information technology at PharmaNet, added, “I think you have to look to the medical industry in general. How many physicians manage entire patient records with paper charts? If you think about the medical profession, it’s a lot of information management. It’s simply by extension that the pharmaceutical industry has adopted some of those more traditional ways of managing information.”

Even though it will be a few years before the whole process is streamlined, current examples of new technologies include electronic data capture, online patient registration and randomization, automated tracking and study management, Interactive Voice Response Systems (IVRS), online training and help for investigator sites, system security, electronic data management, data tracking, data mining, electronic data review and electronic filing of the New Drug Application (NDA). Companies like Phase Forward, Domain Pharma and ESPS, Inc. provide software products and services with these capabilities to CROs and pharma sponsors alike. However, CROs and biotech companies are more likely to use new technologies than big pharma companies are, because integration is not as difficult.

Large pharma companies are laden with infrastructure that makes quick adoption of new technologies difficult. Mr. Nelson commented, “I think adopting new technology would require pharma companies to re-invent some of the processes that exist in the organization for running and managing the data from the clinical studies. It’s not just a matter of bringing in a new technology and using it tomorrow, they have re-invent their processes and re-train some of the folks if they were to bring this technology in and make it a standard. I think that big pharma will be slow to adopt some of these technologies.”

On the other hand, large CROs have been able to bring in new technologies and integrate those new systems into their processes. CROs have a greater vested interest in keeping their processes and infrastructures up-to-date to anticipate the needs of their pharma customers. Even though the integration of new technology may be difficult and a little slow at the outset, sponsors are beginning to expect their service providers to offer fresh and innovative technologies. Anne Willes, vice president of eBusiness at Quintiles, said, “We are finding that, on a bidding basis for day-to-day projects, we’re being asked on some occasions to provide different solutions, so sponsors can determine whether they wish to go the technology route, or whether they’re more comfortable with the paper route. Clearly, there’s a shift taking place. There’s definitely been an increased interest in what innovative solutions we can suggest to sponsors. I think they are looking to CROs for some learning as well as some ideas.”

More and more people, in the U.S. especially, are becoming familiar with new types of technologies as Palm Pilots, cell phones, DVDs, mp3s and the internet have become ubiquitous parts of our culture. This being the case, it seems odd that nurses and physicians participating in clinical studies have not adapted to new processes. Susan Galle, global director-regulatory compliance group at ESPS, Inc., said, “There’s a rate-limiting step, which is culture and the way people are used to conducting this type of business. One of the difficulties is actually performing the clinical trials and collecting the data electronically. The tough part is, it’s not the way physicians have been trained. They’ve been trained that, when they take some sort of measurement, they put it into a written record, not an electronic record.” She added, “That cultural limit will go away as we gain people who are much more comfortable with not using a pen. I think there are lots of efficiency gains to be made, but the technology is not what is holding it back; it’s people’s comfort and their ability to adopt new ways that are very different from the way they’ve worked in the past.”

Ironically, another factor delaying the move from a paper base to an electronic one has been the rapid development of the internet, according to Rich Shea, vice president of business development at Pharma Link. He commented, “The internet infrastructure really has developed at a much more rapid pace over the last 24 months. The software technology to utilize that infrastructure really became commercially viable during that span. It’s a sort of chicken-and-egg thing; if your internet connectivity isn’t very good, then it wouldn’t matter if you had the best software platform in the world, because it still wouldn’t work. You need both.”

Inertia
One of the most important goals pharmaceutical companies have is getting a drug to market as quickly and safely as possible. So how come there has not been a greater drive to speed up the time spent on clinical trials, the most time consuming part of the drug development process? It’s just not that simple.

Philip Lee, president of Domain Pharma, a software provider, commented, “If your company wants to take a paper process and make it electronic and your president says, ‘Do it,’ it’s still a painful process to convert everyone; they’re changing the way they’re doing things. Now we’re talking about an environment where you have physicians who are not part of your company and you are trying to change they way they’re doing things. There’s a certain level of inertia and there’s a certain level of resistance to change.”

Of course, the pharmaceutical industry is a highly regulated industry and the FDA, as well as other regulatory organizations, have defined how studies are done, using paper-based case report forms. Mr. Lee commented, “The pharma companies have gotten used to it and they know how to work around the paper process very well. It may be slower, it may be less efficient and they may have a lot of issues with it, but it works.” As long as drugs are getting approved and pharma companies are still making money, this “if it ain’t broke, don’t fix it” way of doing business will not be updated. Companies must perceive the real benefits of new, efficient and almost flawless technology.

According to Gary Wedig, vice president and chief information officer at Kendle, the clinical trials process will continue to get more and more complicated as compounds become more complex. He remarked, “The drug products that are being developed are more complex, so the government requires that the trial be more complex to prove efficacy and safety. Those kinds of pressures are making the smoothing of the clinical trials process all the more difficult. The regulatory requirements are always there in the forefront. Anything that captures clinical information has to be validated and verification testing is included in the validation. That is becoming such a huge cost of implementing new systems, it’s beginning to rival the costs of analysis, design and construction of new information systems.”

CROs of the Future
Some say that bringing the clinical trials process up to speed, technologically speaking, is still three to five years away. Others think that’s an optimistic prediction. According to Mr. Wedig, the standardization of technologies like the internet and wireless communication are helping to bring the data-capture portion of clinical trials into the next century. Anne Willes of Quintiles echoed Mr. Wedig, stating that efforts for widespread automation of the process will escalate over the next three years or so.

Still, there is a strong interest in new technologies. Shiv Tasker, chief executive officer of Phase Forward, a software provider with clients such as Quintiles, Covance and Parexel, said, “Last year, pharma companies were waiting to see whether new technology would work and if our product would hold up. Now, we’re seeing a mad rush as everyone tries to catch up. People who were sitting on the sidelines last year find themselves six months, nine months, a year behind.” He added, “This year, the pharmaceutical companies are putting their biggest blockbusters, their biggest drugs through the technology because they want to use every advantage they can to win.”

Informatics is becoming a must-have area of development for CROs. In a recent statement, Kendle’s president and chief executive officer, Chris Bergen, said, “Informatics plays a key role in our industry, providing opportunities to further shorten clinical development timelines.” He added, “Process and technological innovations that support the acceleration of drug development are critical to our customers’ ability to compress turn-around time of trial-critical processes.”

CROs can either try to develop new software themselves or look to utilize an “off-the-shelf” system like those from Phase Forward or Domain Pharma. Mr. Tasker of Phase Forward said, “With our software, we try to automate and streamline the whole [clinical trial] process. Basically, we have seen that we can shave monetary costs in half. We have 100% repeat business, proving that the online value is very high because we’re doing three things. First, we’re cutting costs out of the system. Secondly, we are able to lock the databases down faster. And finally, because you have access to information continuously through the course of a trial, you can make very effective decisions both regarding the efficiency and effectiveness of that trial, determining whether or not you should continue the study.”

Parts of the process have benefited from these new technologies, but it remains to be seen if one solution can answer all the problems. Anne Willes of Quintiles contended, “There are a lot of companies out there offering solutions, but the uptake is still in the pilot phase. I think that’s because there are no broad solutions; they only tackle pieces and it requires a significant change in the process to get the best advantage out of those systems. The real answer will come as metrics are collected on where time and cost can be taken out of what is a fairly inefficient clinical trial process.”

Sifting through the array of new, technologically advanced products has been difficult and, of course, this is not an integrated techno-utopia; every sponsor and supplier does not use the same products for project management or to conduct studies. Adrian Otte, chief operating officer for clinical studies and healthcare research at Innovative Clinical Solutions, stated that, while ICS has 10% of its studies done with electronic data capture systems, not all those systems are the same. “One pharma company has a home-grown system while another may be using a commercial system. We then end up having multiple laptops at our site and our coordinators have to be trained by each company to use their particular system for consistency. The benefit of electronic data capture is that we are able to enter information directly into the electronic system and data entry errors are picked up immediately, reducing a lot of the mundane checking for us and the Clinical Research Associates. But these savings can be balanced by the increased staff training and the staff downtime because of the poor reliability and slow connection speeds.”

Interest in internet solutions for clinical trials has been growing rapidly during the past two years, and the future of electronic internet trials is promising. Mark Eisenach, corporate vice president of eCRO services at Covance, said, “I think what you’re going to see are more capabilities and tools that allow us to capture information closer to the event that gave rise to that information, like a patient visit to a physician. There will be more patients recording information in their own homes, as well as tools that allow us to view that information in real time relative to that event, which improves the management of the trial. I also think you’ll see a lot of tools that significantly enhance the communication among team members in a clinical trial and that will establish a standard process for them to interact with one another so that the trial can get started up faster and more effectively.”

As CROs scramble to integrate new technologies like electronic data capture and networked communities for access to clinical trial information, the problem of numerous systems that are not networked has yet to be solved, but not from lack of trying; it will just take time. It’s possible that the wheel has been invented for clinical trials and its Stone Age may soon be over.