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New commissioner is pushing for greater use of technology and innovation to speed the flow of drugs to market.

By Brian Reid

August 13, 2003 | During the nearly two years that the Bush administration searched for a new commissioner for the Food and Drug Administration, the vacant position was defined more by who shouldn't fill the post than who should.

The FDA, at a Glance 

Headquarters: Rockville, Md.

Employees: More than 9,000

Founded: 1906, as part of the Bureau of Chemistry. Assumed the name "Food and Drug Administration" in 1930.

Scope of regulation: Legal drugs, cosmetics, medical devices, food. Regulates 25 cents of every consumer dollar.

Notable ex-commissioners: Donald Kennedy, Science magazine editor-in-chief and president emeritus of Stanford; David Kessler, dean of Yale University Medical School; Jane Henney, senior vice president and provost for health affairs at the University of Cincinnati.
 
Sen. Edward Kennedy, the powerful Democrat who controlled the confirmation process, insisted no "industry types" be considered. The pharmaceutical industry lobbied against appointing drug-safety zealots. And Republican conservatives warned they would not approve avowed pro-choice candidates. Amid the public saber rattling, it wasn't clear anyone could make the cut.

Finally, after ably negotiating the political thicket of confirmation, economist, physician, and White House insider Mark McClellan took the FDA reins last November. He has since spent much of his time redefining the way the FDA operates, trying to squeeze additional speed and efficiency out of a drug-review process that had already undergone a radical redefinition in the 1990s. At the same time, McClellan has engaged in a high-profile effort to bring the FDA to the forefront of information technology use (see "Meet The Commish," May 2003 Bio·IT World).

"There's been a dramatic change in the FDA's interest in applying technology," says Wayne Kubick, vice president and chief quality officer at software developer Lincoln Technologies and a board member of the Clinical Data Interchange Standards Consortium (CDISC). "There's a lot of momentum and energy and excitement, and clearly Commissioner McClellan has a lot to do with that."

"He's interesting," says Robert Yetter, associate director for Review Management at the FDA Center for Biologics Evaluation and Research. "We are certainly working to support him. He's very smart and has ambitious goals, but some of those goals are a little scary to us. But maybe that's what we need to do."

Now, as McClellan nears the first-year mark of his tenure, colleagues at the agency and stakeholders outside the FDA cautiously praise his proactive involvement in FDA-wide technology initiatives that range from e-submissions to systems for reporting drug side effects. At the same time, analysts say McClellan is the most political commissioner in the agency's history.

A New Breed of Technocrat? 
Mark McClellan is distinct from previous FDA commissioners.

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Deep connections to the White House suggest McClellan has been enlisted as not only the nation's chief health regulator but also a reliable Bush ally in aspects of health policy that don't involve the FDA. When Bush demanded that Congress bring him a Medicare prescription drug bill earlier this summer, McClellan — who published academic analyses of the topic before joining the FDA but has no regulatory power over Medicare at the agency — was sent to stump for the plan (see "A New Breed of Technocrat?," right).

So far, McClellan seems to be having fun. "I enjoy luncheon speeches," he quipped at a New York conference this winter. "Other than the chicken, we regulate everything on your plate."


One Step Forward, One Step Back 
During the 1990s, a series of congressionally mandated reforms transformed the FDA from a plodding bureaucracy that took years to approve new drugs to a better-funded organization able to cut review times in half. One reform, the Prescription Drug User Fee Act, or PDUFA, swelled FDA coffers by requiring companies seeking drug approvals to pay "user fees" to the agency. In return, the FDA was mandated to hire more reviewers and to meet certain deadlines in drug reviews, guaranteeing that drug companies would get feedback from the agency in a year or less. It worked.

Since 1998, however, approval times have been inching back up, and while delays are much shorter than a decade ago, pharmaceutical executives have expressed worry about the trend, and Wall Street has placed some of the blame on an increasingly cautious FDA leadership. McClellan's charge: Get the FDA running at peak efficiency.

The McClellan Agenda 
In January, McClellan's office released a three-pronged blueprint, called "Improving Innovation in Medical Technology: Beyond 2002," for speeding up and improving drug reviews. Among the elements...

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Within months of becoming commissioner, McClellan unveiled a plan to ensure that drugs were reviewed as quickly as possible without sacrificing quality. At the core of this road map is an effort to improve communication between the agency and the companies it regulates. Poor communication, McClellan says, causes many delays in getting drugs to market (see "The McClellan Agenda," page 50).

"We think there are ways we can improve the quality of applications early on," he told a New York audience shortly after the January introduction of his plan, which called for more meetings between FDA staff and company representatives and clearer written FDA policies on drug development. "Everybody wins if we do it right."

Disturbing to drug companies is the drop in the number of new molecular entities (NMEs) the FDA has approved in recent years. The FDA says that reflects a drop-off in applications coming from drug companies, not a regulatory problem. In any case, several new approved drugs have excited the industry, even if the approval rate hasn't picked up appreciably.

A controversial cancer drug, AstraZeneca's Iressa, received the FDA's green light on May 5. The approval eight days later of another key cancer drug from a biotechnology company, Velcade from Millennium Pharmaceuticals — after a review of only four months — boosted hopes that the stream of approvals would again pick up. Iressa, in particular, had been viewed as a bellwether. The drug was implicated in 81 fatal cases of lung disease in Japan, and the drug proved less effective than expected in some trials. Nevertheless, the FDA said that the drug's benefits outweighed its risks.

Approval Rating Dips -  One barometer of McClellan's success will be the bottom line: the number of new drugs approved. - FDA-watchers are cautious not to give McClellan too much credit for evidence of a turnaround. Jane Henney, the commissioner who preceded McClellan, says the FDA has been urging better communication with drug makers for years. "I don't know how he intends to hold the industry to what they say they'll do [on communications]," Henney says. "Past history suggests that's not what they'll do."

History also suggests the FDA can chug along with or without a commissioner. Ray Lipicky, the longtime head of the FDA's heart-drug division who retired in 2002 with a reputation for making or breaking billion-dollar drugs, has boasted that he has worked under some commissioners without ever meeting them. The FDA was headless for the 20 months prior to McClellan's appointment and for almost a year before Henney's appointment in 1998.

Still, heading the FDA remains one of the most powerful and highest-profile jobs in medicine. The agency is busy trying to figure out, for example, how much control the FDA can exert over companies that promote unapproved, off-label drug use, as well as seeking ways to more quickly identify dangerous drugs and avoid the embarrassment of the late 1990s when seven high-profile drug withdrawals raised concerns about the agency's vigilance.

So far, McClellan has not faced divisive political issues, and even critics say the FDA under his tutelage has not shown obvious political leanings. That may change; efforts are ongoing to make emergency contraception — so-called morning-after pills — available over the counter, and companies are racing to advance studies of stem-cell-based therapies. Both topics have drawn strong opinions from both the left and the right, but the FDA has yet to deal with either.

One area beyond dispute is McClellan's commitment to technology adoption. Prior to joining the FDA, he was a widely cited author on medical technology innovation. As an economist, McClellan was particularly interested in the financial impact of expensive new technologies.

Deep connections to the White House suggest McClellan has been enlisted as not only the nation's chief health regulator but also a reliable Bush ally. 
"It is widely accepted that technological change has accounted for the bulk of medical care cost increases over time," began one of McClellan's better-known pieces, an article he wrote with Harvard economist David Cutler and published in Health Affairs (Sept./Oct. 2001). "But it does not necessarily follow that technological change is therefore bad."

McClellan outlined his vision for the nation's medical technology information infrastructure at a June gathering sponsored by Connecting for Health, a public-private partnership charged with improving information sharing among the nation's doctors, health plans, and government.

"Physicians spend an estimated 20 to 30 percent of their time searching for or organizing information," he told the group. "That isn't only bad medical care. It's also needlessly expensive. It doesn't need to be that way, and I don't think it will be in the future."


Wired Reporting 
McClellan has repeatedly pointed to a new collaboration between the FDA and New York-Presbyterian Hospital as a model of what a wired healthcare infrastructure can achieve. As part of the Connecting for Health initiative, the hospital and the agency have established an electronic link — and a common set of data and terminology — that allows the healthcare provider to automatically send patient information to the agency.

That could change the way drug safety is analyzed after a drug is already on the market. Now, the FDA relies on a voluntary system to report adverse events. A doctor or patient who sees an unexpected or worrisome problem can file a report with the agency, but most problems are never reported, making it difficult to detect signals that may suggest complications with a specific drug.

Instead of voluntary reporting, or even required reporting, McClellan has proposed "automatic reporting." Lab results from patients taking a certain drug regimen could be automatically sent from a hospital's computers in the FDA's system without human intervention, and vast amounts of data could be quickly scanned for unusual or problematic results.

"If we can move to such a system, think of the many ... benefits to patients," McClellan said at the Connecting for Health event. "The FDA could be automatically informed about the misuse of certain drugs. Or automatic reports of lab tests could indicate the frequency of serious kidney problems in high-risk patients on certain drugs."

The two groups began the data exchange in June, using, in part, equipment donated by IBM, and both the regulators and the healthcare providers say they have high hopes for an expansion of the effort.

"It's more efficient. It's less expensive. It's closer to real time," says J. David Liss, vice president for government relations and strategic initiatives at New York-Presbyterian. Liss says the hospital plans to eventually send data entered into its home-built clinical information system to the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention. "We're starting with the FDA, and then we're going to branch out into other things."

The FDA is committed to doing more than simply receiving data, piggybacking on expensive clinical information systems at leading hospitals. McClellan is also touting a program dubbed "DailyMed," in which the FDA, in partnership with the National Library of Medicine, would be able to electronically modify drug labeling in real time, giving prescribers information about a drug's risks and benefits as the agency receives it.

In Search of Guidance 
Hoping to give pharmacogenomics a needed boost, the FDA's new commissioner has thrown his weight behind efforts to quickly set agency policy on the matter.

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McClellan "is very interested in trying to use technology and standards to try to advance the work we're doing not only inside the FDA, but in all healthcare," says Randy Levin, associate director for information management at the FDA's drug branch and one of the agency's unofficial ambassadors to the informatics community. "He's not just talking the talk. He's walking the walk." (See "In Search of Guidance.")

McClellan has also emphasized the agency's proposed bar-coding rules that would require nearly every drug package sold in the United States to carry a bar code, making pharmaceuticals as easy to track through the healthcare system as the average box of cereal is to track through the supermarket.

Such tracking, says the new commissioner, should reduce medication errors, one of the biggest problems detailed in a 1999 Institute of Medicine report, which concluded that between 44,000 and 98,000 patients a year die due to medical errors. Given the rise in prescription drugs — 60 percent more prescriptions will be written this year than a decade ago — it's critical to act now, McClellan says.

The effort won't be cheap. In the proposed regulations, the FDA warned that the cost of putting scanners into the nation's hospitals could exceed $7 billion, with much of that cost falling on hospitals. Nonetheless, the American Hospital Association expressed support for the rules. "There's a lot of interest in getting this going," says AHA spokeswoman Amy Lee.

Levin is also spearheading the agency's push for electronic submission of drug applications, a process to which Levin says McClellan is also paying close attention. According to Levin, an estimated 75 percent of new applications are coming in electronically. "The number increases significantly every year," he says.

Those leaps in technology promotion by the agency are a welcome change from a decade ago, when high-profile efforts to wire the application process ended in failure, according to Lincoln Technologies' Kubick. While the agency has no plans to mandate electronic submissions, Levin says the technology is already having an impact on the scientists reviewing the applications.

"Once the [drug application] reviewers see what they can do with a good electronic submission, it's hard to go back to the paper," Levin says. "McClellan views this as a way to improve the way we do our work." * 



Brian Reid is a senior editor for Bio·IT World sister publication Health·IT World. He can be reached at brian_reid@health-itworld.com.

ILLUSTRATION BY ROB DAY 


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