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'E-source' Is Coming, Experts Say

By Mark D. Uehling

July 20, 2005 | Odd marriages of the ancient and modern are the rule in clinical technologies and were much in evidence at the E-Clinical Trials & Research conference program of the 2005 Bio•IT World Conference + Expo. There was heartening evidence of the adoption of advanced and robust commercial software — even toward clinical trials that do not use paper. But most clinical trials still collect and manage data using paper.

As pointed out by Becky Kush, the president of the Clinical Data Interchange Standards Consortium (CDISC), resolving some “queries” or discrepancies may cost from $70 to $8,000. With selected drugs, the industry collects the same safety data once, twice, seven times. Could academia be leading the way to eliminate such inefficiencies? At Duke University, Kush said, an electronic health record is being integrated into systems for clinical trials: “They have not pulled a chart in three years.”

EDC Usage Data

CDISC publicly presented data from its latest survey for the first time. The CDISC poll may be biased in favor of paper-averse, software-loving types in the clinical trial community. But it is nevertheless the best approximation of what technologies are actually being used in clinical trials.

The most-awaited number was the percentage of trials using some form of electronic data capture (EDC). That figure rose slightly from 27 percent in 2003 to 30 percent in 2004. “It’s not increasing. It’s still pretty flat,” said Assero Ltd.’s David Iberson-Hurst, who compiled and presented the results.

The CDISC figure includes the relatively painless “ePRO” trials, or electronically patient reported outcomes, which may involve little more than touch-tone telephones. Even so, there was a fair amount of negative opinion about ePRO technologies, especially from clinical sites that need to train patients on how to use hand-held devices. Said Iberson-Hurst: “Maybe the experience with the technology is not all we should be aiming for.”

Paradoxically, Iberson-Hurst noted that while two-thirds of the industry is stuck in the 1960s, a minority is forging far ahead into “e-source” — trials that dispense with paper. “E-source is very much with us,” he said. The bad news is that there is nothing close to regulatory clarity about e-source under 21 CFR Part 11.

As Iberson-Hurst explained, “An investigator who captures that data is obliged to maintain the source data, prevent its destruction, and allow access to inspectors. If we have e-source data, can they retain it? What is the meaning of the word ‘retain’? How can they prevent destruction, given they have no access to what is being retained? The debate is going on. Vendors claim they are taking on investigator functions. But there is no mechanism under the law for that.”

Given his self-deprecatory tone, it’s clear Iberson-Hurst has been privately thrashed by the e-diary community for daring to identify ambiguities in the regulations. But the FDA is said to be working on a nonbinding “guidance” document for e-source, which could be published as soon as this summer. Although there is plenty of good news about patient diaries (see “Abandon Paper! Use a PDA!,” June 2005 Bio•IT World, page 48), such uncertainty could allow ambivalent sponsors to continue using paper until the dust settles.

Featured speaker Sylva Collins, vice president of advanced clinical systems at Novartis, presented her impossible-to-match metrics from EDC (see “Master of the EDC Universe,” August 2004 Bio•IT World, page 26). In a sign of the shifting jargon, she referred to electronic case report forms (CRFs), which are basically computer screens into which paper-based clinical data are entered.

In 2001 alone, Novartis spent $17 million just printing paper CRFs. The company is now locking databases in less than a week and recording just four queries per 1,000 data points; it used to take as long a year to lock some databases, partly because of 51 queries per 1,000 data points. Collins expressed little patience for those who wonder why pharma builds software: “If you’re in the modern drug development business, you’re in the software development business. Get used to it.”

Luminous Lubin

A contrary voice at the meeting was Gary Lubin of Merck Capital Ventures, a venture fund at the drug giant. He’s invested in PHT, Acurian, and Cytel, among other clinical technology companies. Lubin said he did not care for Novartis’ approach to EDC. “It’s a flawed solution,” he said. “It will preclude the use of a lot of vendor offerings and new technologies.” Which is not to say Lubin ever gets misty-eyed about the cosmic significance of EDC: “This is transaction processing,” he said. “It should not be a big deal. It has become a big deal.”

Lubin would like to see more attention focused on larger, thornier problems. “Protocol design and development is first and foremost, with adaptive trial design being an important area in our industry’s crosshairs,” Lubin said. Speaking of patient and investigator recruitment, he said, “It will see a tremendous amount of activity. The strategy behind finding patients and investigators is becoming truly a strategy and part of the formulation of the trial.”

‘Poor Profitability’

Another financier was just as bleak about the EDC industry. “It could be that nobody is going to make enough money,” said Michael Martorelli, an analyst at Fairmount Partners. “Poor profitability could hamper any or all independent vendors of EDC solutions.” Like Lubin, Martorelli has grown weary of trying to predict when pharma will adopt the technological efficiencies of banks or retail stores. “We were way too optimistic on what this adoption cycle would look like,” Martorelli said.

That cycle looks completely different at the National Institutes of Health. A former CIO at Bristol-Myers Squibb, Sue Dubman is now director of applications at the Center for Bioinformatics at the National Cancer Institute (NCI). She said the NCI is developing a variety of tools for better collaboration among cancer researchers in government and academia. All the tools will be in the public domain; some could surpass what is available from industry. The goal, she said, is not to have a free text document or a PDF describing the patient eligibility and exclusion criteria. Better to have a structured XML document that computers could parse to find patients online.

Another NCI application — Firebird — will manage the submission of clinical investigator 1572 forms, allowing physician-scientists to register themselves online. Dubman and her colleagues recently organized their own conference on all the NCI technology efforts, expecting 200 to attend. Instead, 500 people materialized. “We had to turn people away,” Dubman said. “The fire marshal was after us.” Not everyone in the clinical trial community is as stuck as the people in industry.

Indeed, Jerald Schindler, assistant vice president of clinical technology at Wyeth, insisted that a very cutting-edge approach — the adaptive clinical trial — is a reality. Such trials depend on EDC and offer sponsors interim peeks at, and changes to, the required numbers of patients in each arm of a trial. The savings in time and finances could be massive. “Companies are doing adaptive trials now,” Schindler said. “They’re starting to expand the frequency and the number of variables they’re looking at.”

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