FDA's proposed definition of "suspected adverse drug reactions" would encourage more premarketing adverse event reporting.

The revised and expanded definition, included in the agency's March 14 proposed rule on safety reporting, would require companies to file expedited reports of suspected adverse drug reactions, unless the company is sure the product did not cause the reaction.

SADRs would be defined as "a noxious and unintended response to any dose of a drug [or biological] product for which there is a reasonable possibility that the product caused the response. In this definition, the phrase 'a reasonable possibility' means that the relationship cannot be ruled out," the proposal states.

The new definition would harmonize FDA's current definitions of "adverse drug experience," "adverse experience" and "associated with the use of the drug" in its premarketing and postmarketing regulations.

"FDA believes that the proposed definition of SADR would not affect the number of safety reports that are currently submitted to FDA from spontaneous sources, but it could increase the number of safety reports that would be submitted from clinical studies."

Sponsors typically interpret the phrase "reasonable possibility" to mean "that there is a possible causal relationship between an adverse experience and a drug or biological product," the agency noted.

The proposed definition "defines the phrase to mean that the relationship between a product and a response to a product cannot be ruled out," FDA explained.

The agency proposed several categories of SADRs, including life-threatening, serious, nonserious, and those SADRs with unknown outcomes. FDA's existing regulations separately categorize life-threatening and serious adverse drug experiences.

Citing one example, FDA says the rule would require companies to report liver deterioration in a patient with viral hepatitis who is in a clinical trial. A company "may not currently submit a report because it believes that there is a reasonable possibility that the liver deterioration is due to the patient's disease and not to the hepatotoxicity of the drug the patient received," the agency noted.

The criteria were broadened "in order to be better able to generate signals of new potential safety problems with drug and biologic products," FDA said.

The proposed rule also would require companies to report within 15 days "certain medically significant reactions that are often associated with drug toxicity," such as liver failure, aplastic anemia and seizures, "whether or not such events have been previously reported to FDA in association with the drug."

Currently, companies submit those reports on a quarterly or annual basis, once such a reaction has been reported to FDA and added to the label.

The shift would allow FDA to receive a steadier stream of reports while making risk management decisions. FDA aims to publish guidances on risk assessment, risk management, and pharmacovigilance that would set out a tiered structure for risk management programs (¹ Also see "FDA Risk Management Plan: Four Levels, From Labeling To Restricted Access" - Pink Sheet, 10 March, 2003., p. 3).

Firms are also encouraged to make risk management suggestions. "The new rule would require that postmarketing periodic reports now contain a thorough analysis of the interval data and recommendations on what actions, if any, need to be taken based on any new knowledge gained about the product."

The proposed rule puts forth a risk-based approach to reporting: companies are expected to spend more time tracking down details of unexpected serious events and less on follow-up to minor events known to be associated with a product.

Annualized industry costs associated with the rule are $155 mil., the agency said, predicting that economic benefits would be $948 mil. annually if the rule led to a 2% reduction in total hospital costs of SADRs.

Dubbed "The Tome" by FDAers because of its near 500-page length, the proposed rule also details procedures for reporting medical errors. The safety reporting rule was published along with the agency's proposed rule on bar coding (see ² Also see "FDA Bar Code Proposal Requires NDC; Lot, Expiration Date Not Cost Effective" - Pink Sheet, 17 March, 2003.).

FDA Drug Safety Rule Would Promote Premarketing Adverse Event Reports

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