Side-effect reports to the FDA are a contentious subject. Despite a series of efforts to improve adverse-event reporting, numbers from the agency's database tend to be quoted with an accompanying list of disclaimers. But is the Federal Adverse Event Reporting System more reliable than we think?
A study published today in the journal Drug Safety says yes. It zeroes in on the "Weber effect," which discounts side-effect reports on the newest products. It's not usually referred to by name, but pharma followers know it: A barrage of safety reports usually follows a drug's debut, and reports fall off dramatically after two years. So, the FAERS data can't be used to weigh the safety of new drugs against older drugs' safety records. Nor can new drug classes be fairly compared with older drug types.
But the Weber effect isn't an actual effect, the Drug Safety study found. After analyzing 62 brand-new drugs launched from 2006 to 2010, the researchers found that adverse-event reports do ratchet upward quarter by quarter for products' first three quarters on the market. After that, the number of AE reports stays relatively steady for the next 13 quarters. So, rather than falling off after two years, side-effect reporting hangs tight for four years, the study concluded.
The study results run counter to assumptions about the usability of the FAERS data, and could potentially change those assumptions, study author Brian Overstreet said. "The Weber effect was discovered in 1984, in a study of a small group of drugs, but there's been a 30-year reliance on this as gospel," said Overstreet, who's also CEO of AdverseEvents, a company that analyzes FAERS for payers, healthcare systems and pharma companies. "It's been accepted as dogma that the data can't be used."
Some individual products have followed the Weber pattern. GlaxoSmithKline's ($GSK) allergy spray Veramyst (fluticasone furoate) and Merck's ($MRK) diabetes treatment Januvia (sitagliptin), for instance. But others do just the opposite. Letairis (ambrisentan), the Gilead Sciences ($GILD) treatment for pulmonary arterial hypertension, saw side-effect report numbers increase each quarter of its second two years on the market. the growth curve on Pfizer's ($PFE) cancer treatment Sutent is similar.
This new study isn't the first to question the first-two-years theory. For one thing, an internal FDA analysis didn't replicate the Weber effect, the article notes.
Could the Weber effect have gone out of style? The study authors suggest that FDA's efforts to improve reporting may have changed the reporting pattern. From new adverse-events reporting guidance in 2006 to the REMS plans rolled out in 2007 to new direct-to-consumer pleas for reports beginning in 2008, these moves appear to have boosted the number of reports. Plus, the agency has cracked down on pharma companies that lag in their own side-effect reporting.
All in all, 800,000 adverse-event reports were filed in 2012. The first quarter of 2013 saw at least 250,000. At that pace, last year's numbers will hit 1 million. And now the agency is looking to boost reporting even more, plus open up the database for outsiders to analyze its contents, through its latest Open FDA effort.
- download the Drug Safety article (reg. req.)