Want to get depressed? The Tufts Center For the Study of Drug Development has analyzed the length of clinical trials during two time periods: 1999-2002 and 2003-2006. The median number of days from first to last patient visit has doubled, to 598. Nineteen months.

Can anyone think of any industry that takes twice as long to do something in 2006 as it did in 1999? Slow food, maybe?

If there is an elephant in the room of clinical trials, it is the clinical trial protocol and the inefficiency lurking within. Is everything necessary? What’s on page 143? Will the protocol burden the clinical sites? Will the data be clinically relevant? Credible to regulators? We wrote about this a few months ago. We also did a podcast with Genentech on a related topic, the smart protocol.

Kitchen-Sink Approach

A few months after our earlier story, Medidata is still talking about better protocols, still absorbing the acquisition of Fast Track Systems. Medidata is cognizant of the danger in confronting the elephant, but seems interested in a gentle, family-style intervention.

Its goal is to quantify the complexity of every element of a trial, and the work effort associated with it, and integrate that into the electronic data capture technology supporting a trial. That will allow the overall complexity of a trial to be assessed one budget item at a time without affecting the study’s most important objectives.

Such an approach challenges the power structure at many companies. It will not be easy to review elements in a protocol that were added at the behest of a scientist who has never been accountable for their project-wide cost or site impact. Now those numbers can be made very, very visible in a nice table.

Studying The Study

“You allow the technology to surface that naturally. You need ways to manage and visibility to performance activity that is going on outside your own four walls,” says Ed Seguine, an ex-Fast Track executive who is now general manager of the trial planning solutions group at Medidata. “I’d become jaded about the industry’s ability to understand these concepts. But my faith has been reignited somewhat.”

That’s because the technology vendor is reaching higher-level personnel on the sponsor side of the industry, people who appear to be receptive to the notion that the clinical trial process could stand some improvement. New types of computer reports, Seguine says, can help drive better trials at the start, especially if senior managers or therapeutic experts can see the chronological or financial ramifications of a trial element.

Cost Containment

Unlike most of the industry, Seguine doesn’t think attempts to negotiate with sites or manually review protocols will produce notable savings. But using a proprietary database (as does competitor ClearTrial) Medidata can offer data about trials to help sponsors know that a 3-page questionnaire need only be administered four times during a trial, not fifteen. Or that a 6-lead electrocardiogram isn’t routinely used, industry-wide, in a particular type of oncology trial. Such findings can open a conversation that can’t be short-circuited by someone in a white coat giving an edict, I’m in charge and we’re doing it this way because I say so.

Or, as Seguine puts it: “Those are sacred cows. You generally don’t question them rigorously.” He’s got rigor. For each aspect of a trial, the system breaks out costs and complexity on a per-patient basis, and by phase of research, therapeutic area, and impact on clinical sites.d9A2t49mkex

Instant Updates

As a part of its evangelism effort, Medidata has been trying to help physicians and scientists understand the long-term benefits of structured data. “If you say structured data to a physician, their eyes are going to roll back in their heads,” he says. By structuring the data, he believes, the overall role of that data can be tracked and categorized against the company’s database of experience recording similar items on similar trials.

The company’s data and service offerings, he says, are designed to show clinicians and others the relative complexity and cost of every element of a trial. If a sponsor decides the trial can survive the removal of a particular element, the protocol (and electronic data capture system) are updated instantly. “You can take it out at the very last minute,” says Seguine. “The scientific gestalt that we’re all comfortable with can happen at the last minute.”

Trouble Ahead?

One of the most troubling metrics for the future of the industry is that clinicians are getting less money for each item in a protocol, even as studies are stuffed with more elements over time. “As [protocol] complexity has gone through the roof, the average cost per procedure has actually declined,” says Seguine. “It’s no wonder investigators are like ‘Man, is it really worth my while to be involved in clinical research?’”

“If you went out and looked for people who were collecting data they didn’t use, you’d find that in every company,” says Glen de Vries, Medidata’s co-founder and president. “You’d probably find it in every protocol.”

The combination of Fast Track and Medidata, de Vries says, will allow deeper analysis of trial costs during and after the study. “We can look at how many queries were opened on primary endpoint versus secondary endpoint. We can look at how much field time was spent monitoring various protocol variables. We can associate data monitoring costs on endpoint.”

Excessive Complexity

De Vries is insistent that his firm is offering a new ability to start with a protocol, optimize it, and move rapidly to a live EDC system. Knowledge gained along the way can be fed back into the system. Says de Vries: “It is useless to just have the plan and not be able to track what’s happened. We have the plan and the ability to track against the plan.”

The company seems to be taking a more proactive approach to examining the protocol at all stages of a trial—not isolating the protocol in the start of the project without consideration of what follows. Ensuing conversations can be driven by numbers. Says de Vries: “Can you figure out your protocol is more complex than it needs to be? Or manage your data management proactively to new metrics that you weren’t able to distill out of your other system? We think there is huge potential to provide a novel opportunity to more progressively manage drug development.”

Systemically staggering costs and longer timelines across all clinical trials have been ignored by financial analysts. For now. Wall Street has been fortuitously obsessed with the fortunes of individual biotech and pharmaceutical companies. But in a coming era of lower sponsor revenues, due to both a newly vigilant FDA and patent expirations, any sponsor that can prove it runs more efficient trials will be at an advantage.

Editor’s note: Pfizer is running a session on metrics and EDC at the forthcoming Society For Clinical Data Management conference in September. Here’s the preliminary agenda.

d9A2t49mkex