WASHINGTON — Karen Hicks, PhD, a medical officer at the division of cardiovascular and renal products at the FDA’s Center for Drug Evaluation and Review (CDER), gave attendees a look at the “nuts and bolts of the review process” from the point of view of her center’s reviewers during TCT 2007, ongoing this week.

Hicks pointed out that numerous divisions at both CDER and CDRH are involved in stent reviews, that CDER considers its evaluation of a premarket application much like “a new drug application” and that industry can help with speeding these approvals.

“We expect all the safety and efficacy data we would get with a new drug application,” Hicks said, and that for CDER, “safety is a more challenging issue” than efficacy.

Additionally, because of the relative novelty of some of the “olimus” class of drugs, CDRH “is asking us new questions.”

Among CDER’s problems in reviewing device/drug applications is that “a lot of patients [are] lost to follow-up,” and she said CDER reviewers think these losses “should equal zero” in terms of supporting data. Reviewers also take issue with missing lab values for enzymes, “and we want to see the survival curves” beyond endpoints.

Hicks said that sponsors reliably fill out case report forms for cardiac adverse events but not so well for non-cardiac adverse events, such as hypersensitivity to the drug. Among things that CDER reviewers need, but sometimes don’t get, are adverse event data sets that include verbatim terms, as well as consistent use of Medical Dictionary for Regulatory Activities (MedDRA) terms, a clinically validated international medical terminology used by regulatory authorities, including FDA.

“It would help to have the data procedures” as well, Hicks said, to understand the statistical approach.

Among the other data Hicks said CDER likes to see are: normal lab results and patient baselines, “elevated liver enzymes and leucopenia,” and in-depth electrocardiogram data. “Please look at the E14 guidance,” Hicks urged, which addresses QT and QTc elongation for non-anti-arrhythmic drugs that may nonetheless have pro-arrhythmic potential.

Using E14, she said, “There are a couple of quick-and-dirty things you can do” to fill out the data set without adding a lot of work for those who have to assemble the reports.

“In summary, we’d like you to minimize lost follow-up,” she said.

— By Mark McCarty, Washington Editor