An FDA-PhRMA working group is finalizing a "white paper" on data mining as a tool in postmarketing safety surveillance.

The working group "soon will be disseminating a white paper on best practices in data mining and best use of analytic tools for post-event surveillance," FDA Office of Pharmacoepidemiology and Statistical Sciences Director Paul Seligman, MD, said during a Drug Information Association/Agency for Healthcare Research & Quality workshop on pharmaceutical outcomes research in Tucson, Ariz. Jan. 21.

FDA and the Pharmaceutical Research & Manufacturers of America formed the working group at the start of 2003 (¹ Also see "PhRMA-FDA Working Group To Develop Best Practices For Data Mining" - Pink Sheet, 21 April, 2003., p. 30). The agency has also contracted with Lincoln Technologies to work on data-mining technology (² Also see "FDA Adverse Event Data Mining Systems To Be Created By Lincoln Technologies" - Pink Sheet, 12 May, 2003., p. 21).

FDA has already taken steps to upgrade its handling of adverse event data, Seligman noted.

"We have begun to use...data mining" to provide better information from "our 3 mil. adverse event reports," Seligman said. "We're conducting disproportionality analyses to look at combinations compared to the entire data set," he said.

University of Arizona VP-Health Sciences Ray Woosley, MD/PhD, agreed that FDA has made significant progress in technology. "Some of the new display tools that they're using [are] impressive." The system is "hypothesis-based, it is informed, and it is darn good."

FDA has conducted an overall strategic assessment of its Adverse Event Reporting System and expects to announce further upgrades soon (³ [A#00650470015], p. 19).

"We are really moving away from considering our adverse event reporting system as our only tool in the postmarketing arena," Seligman noted.

FDA will be "using that system as just one of a series of tools in trying to identify problems in the post-marketing environment."

The agency intends "to utilize the richness of data that exists in medical records and computerized and electronic records to try to sort out and identify problems that may be occurring with products that are currently in the market."

"We're about pushing it as far as we can push it" with the current spontaneous reporting system, Seligman said. "It has inherent limitations. No matter what tools you throw at it, it's only as good as the quality of the data that are in there. We're now starting to broaden our horizons and look elsewhere."

FDA is also completing work on draft guidances on risk assessment and risk management, Seligman noted. The guidances should be issued "in the coming weeks."

"These documents are consistent with the concept papers that we published last April," he said. FDA published concept papers on premarketing risk assessment, postmarketing surveillance and risk management in March (⁴ Also see "FDA Risk Management Plan: Four Levels, From Labeling To Restricted Access" - Pink Sheet, 10 March, 2003., p. 3).

The guidance "focuses on the use of scientific data not only to optimize postmarketing regulatory decisions, but also premarketing regulatory decisions. It calls for a focus on integrated risk assessment and economic analysis to identify efficient risk management options for policymakers," Seligman said.

"You will see a strong emphasis in the upcoming guidances on developing models for evaluating effective risk management programs....We will be asking not only sponsors to work closely with the FDA, but also to work with academic institutions and the leading figures in our country on how best to evaluate public health initiatives."

Seligman characterized FDA Commissioner McClellan as an "early adopter" of new approaches to drug safety.

"He really focuses on evidence-based cost-effectiveness kinds of issues, and is really in many ways a strong proponent of technological solutions and utilizing the progress that has been made in informatics to inform our ability to detect problems with products in the postmarketing environment, as well as utilizing technology to improve the ability to develop a product within clinical trials," Seligman said.

Woosley outlined what he considers to be "essential elements of a postmarketing surveillance program": hypothesis-based analysis of spontaneous reports, data enrichment, prospective analysis of comparative data, targeted clinical trials and post-mortem analysis of product withdrawals.

Woosley also offered an analysis of the problem of under-reporting of adverse events. "We just completed a fairly exhaustive review of medical literature on why physicians...don't report events," he said.

One reason "is that the health care system in which physicians operate doesn't afford them the support or the time to report," Woosley said. In addition, "many of them don't actually see the benefit to their already overburdened practices in actually doing that reporting."

"Do we have a concerted effort and strategy at the FDA to do this? The simple answer is no." FDA, AHRQ and academia should work on improving physician reporting, he suggested.

Woosley endorsed FDA aspirations to "develop a global drug safety program that incorporates many more tools."

Woosley also called for an "independent Drug Safety Board that would do the post-mortems," following the model of the National Transportation Safety Board. "When a plane goes down, you don't ask the manufacturer who's at fault, and you don't ask the Federal Aviation Administration that sets the standards - but you say to everyone, 'Let's all look at this, so we learn something from it.'"

"It's in the best interest of everyone, including pharmaceutical manufacturers, to detect serious adverse drug reactions as early as possible, before the trial lawyers get you in their crosshairs," Woosley said.

"A global consortium of national agencies and industry that uses a variety of methods" would detect events "earlier and more reliably" than current surveillance methods, Woosley said.

Woosley also suggested that "FDA needs more tools. They need more people."

Seligman concluded by noting that the agency is actively recruiting for several drug safety management positions. "We have a deputy of the Office of Pharmacoepidemiology and director of the Office of Drug Safety, as well as a deputy director for Drug Risk Evaluation currently open....I have brought along today the FDA recruitment package."

FDA Moves Ahead With Adverse Event Data-Mining; “White Paper” Out Soon

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