Pregnancy Registries May Use External Comparison Groups – Final Guidance

Pregnancy exposure registries may use external comparison groups, including background rates, surveillance systems and other registries, FDA said in its ¹ pregnancy registry final guidance.

"Enrollment of a concurrent comparison group of unexposed pregnant women, while most desirable methodologically, may not be possible, and may exceed the scope of most registries," FDA acknowledged. "A background rate or the prevalence of congenital anomalies in a population-based surveillance system or other pregnancy exposure registry may be the only available comparator."

The guidance's options for comparison groups address concerns raised by the Pharmaceutical Research & Manufacturers of America in comments on the June 1999 draft guidance ("² (Also see "Pregnancy Registry Data Use In Labeling Should Be Compiled By FDA - PhRMA" - Pink Sheet, 13 Sep, 1999.), p. 21).

PhRMA's comments call the draft guidance's recommendations for comparison groups "particularly troublesome." The draft guidance, PhRMA said, "seems to be alternatively describing a pregnancy registry to collect information on specific drug/biologic exposures, and a cohort study that enrolls women exposed to a certain product during pregnancy and a comparative non-exposed cohort. The impression given is that concurrent comparison groups are always necessary."

Registries typically do not have concurrent internal comparison groups; comparisons are mostly to external rates, PhRMA said.

The final guidance, published in the Sept. 23 Federal Register, also addresses PhRMA's concern that regulatory reporting requirements in the draft were "inconsistent" and confusing.

FDA clarified that registry reports are "derived from active solicitation of patient information," and accordingly will be subject to 15-day reports when the events are serious, unexpected and possibly caused by the drug or biologic.

[Editors note: The October issue of Pharmaceutical Approvals Monthly will contain further coverage of the guidance. For a copy, please call Dzidra Vizbulis at [phone]].