Some contract research organizations (CRO) had to be dragged into using technology. They presented at conferences, pooh-poohing software. They doubted, delayed, complained. They did not necessarily advocate fountain pens and carrier pigeons. But they could quote a price on ink and birdseed.
And then there are people like Jules Mitchel, president of Target Health. He delights in the power of technology as much as any software vendor, except that his day job is running a mid-sized New York City CRO with 45 employees. Mitchel and his team represent 30 sponsors at the FDA, with perhaps 40 projects under way at any given time. The company's clients have won three product approvals during the 2010 calendar year: one in Canada and two in the U.S. In aggregate, over the existence of the company, Target Health has helped clients bring 27 products to the market.
Nineteen of those products included trials that relied on Target Health's proprietary electronic data capture (EDC) solution. Mitchel's stuff works.
When we checked in with him recently, he assured us that the work of the Clinical Trial Transformation Initiative (CTTI) was not ... ahem ... moribund. (Note to self: hold off publishing that CTTI obituary.)
As readers may recall, some very smart people at Duke Clinical Research are trying to corral a diverse group of high-level industry, academia and FDA representatives into experimenting on a few truly revolutionary projects. Those efforts are ongoing. If codified into regulation some day, they could push the modern clinical trial abruptly into the 1990s, when other industries discovered the Internet.
Mitchel's company is on the steering committee of the CTTI. He says the group is making steady progress. He can't speak for the organization. But he can opine that its work has already shown that automatic monitoring of all records at all clinical sites according to some rigid, preset schedule is not necessary from a regulatory perspective. Or cost-effective.
In other words, mindless monitoring of everything is not mandated by U.S. law or Good Clinical Practice guidelines. Says Mitchel: “There was no scientific rationale for monitoring plans in clinical trials. It was mostly based on peoples’ previous experiences and what they were taught.”
Mitchel thinks that the FDA might eventually clarify what the agency has long said at conferences: that its rules never demanded routine, rote, automatic monitoring of every data point under the clinical sun.
What might make more sense? A risk-based approach, Mitchel speculates. That might involve doing source document verification on 100 percent of all initial case report forms (CRF). Using that inspection of the data, a sponsor or CRO might identify a few critical scientific variables and verify only those. The concept is to confirm the protocol is indeed being followed, and then check the most important data. “It’s 100 percent unnecessary,” he says about 100 percent source document verification.
Instead, Mitchel says, an assessment of the protocol and the sites themselves should drive a more limited, selective examination of the data. Some of that examination could happen remotely, using technology. Says Mitchel: “We need to show evidence-based monitoring works. We have to prove it. That’s what CTTI is all about—not showing it theoretically.”
Mitchel is particularly excited about another technological development, one that the CTTI is not yet exploring. He is adamant that electronic health records (EHR) are poised to hit the clinical trial world. Doctors are buying the systems with massive federal subsidies.
In test demonstrations, EHR and clinical trial systems can be connected. We've written about the technology here and here. In ordinary trials in the real world, the question is whether the sponsor community can conform to the relevant data standards with sufficient rigor to populate EHR systems from their FDA-regulated research systems.
Some sponsor companies, to be charitable, have inflated views of their own abilities to adhere to well-established clinical data standards across geographies, departments, time zones and therapeutic areas. Since sponsors won't embrace those optional guidelines to the letter, can they get their minds around an entirely new encyclopedia of different recommendations for a completely different industry?
For his part, Mitchel sounds convinced that EHRs could take considerable work off the shoulders of clinical site personnel. As a result, the pharmaceutical industry will be obliged to adjust its research tools and processes to support EHR systems. “It will go much faster than EDC,” he predicts, suggesting a 3-5 year adoption time line.
Anticipating that, Target Health has developed a new piece of software to pass data between research and hospital systems. It works independently of Target's EDC system and should be able to connect to any standards-based EHR program. To test his conduit, Mitchel has been working closely with a small EHR firm in Israel, Life On Key.
A Smaller Spec?
Mitchel is well aware that there is debate about how clinical trial research systems will be connected to physician office and hospital systems. Some people believe the hooking up of EHR and EDC systems is just around the corner. Others counter that EHR-EDC integration will never happen routinely.
Mitchel says neither the clinical trial world nor the hospital-physician systems need to be overhauled. Rather, he says, it’s just necessary to transport a bit of data between the two realms. “It is not a technical issue,” says Mitchel. “It’s work flow. Most clinical trial data have nothing to do with clinical practice. Our solution is to just give them a PDF file that has to do with the clinical trial.”
What about a trial in which 100 clinical sites have 100 different EHR systems? That, after all, is what the real world will look like. He says his EDC-EHR linkage tool could handle that.
Mitchel fully grants that the industry will have to sort out what the optimal process should be. The FDA may have to say what constitutes a source document in a digital age. “They must address what is the source [document],” Mitchel says of the FDA. How long that would take is anyone’s guess. But no new guidance is necessary, Mitchel says, just a clarification of how to comply with what the agency has already said.
Trial-specific data, of course, may always need to live on the EDC side of the firewall, simply to facilitate queries and data cleaning. But data could be zapped over to an EHR for billing reasons or to maintain a complete medical history. Mitchel believes it will take a year or two to sort out those issues, and that EHR-EDC connections will eventually be as unremarkable as hooking up a new cable TV box.
For detractors of EHR-EDC connections, the systems are so ill matched as to be unlikely to ever be routinely connected. For the doubters, mundane EHR-EDC connections are as improbable as mating a whale and a parrot. All the money in the pharmaceutical industry will not be able to make a viable whale-parrot hybrid, but that may not prevent a few determined zoologists from trying.
Mitchel is too practical, and too optimistic, to be bogged down in quibbling and analogies. He patiently waited for EDC to be accepted, and believes EHRs are just as inevitable. At some point, he insists, industry will make a shift more profound than what the CTTI is currently contemplating.
To wit, the retirement of the case report form. Clinical trial data will live on. But a form? In an electronic age? “This is the end of the CRF as we know it,” he says. “The CRF has to do with paper. There is no need for a CRF any more.”
Target Health is about to start two trials in which there are no paper source documents. One is a Phase II project, the other is a pivotal Phase III. Mitchel foresees no regulatory issues on those projects. Regulatory officials are aware of the paperless aspects, he says. Mitchel anticipates 50 percent cost savings in the data monitoring budgets. Such savings could be appealing to sponsors feeling economic pressures. Sometimes, it seems, the future arrives before even forward-looking companies expect it.d9A2t49mkexd9A2t49mkex