Friday, September 04, 2009

"Lagging Indicators:" Does Europe Approve Drugs Faster Than The US?

We heard a phrase we haven't heard in a long time this week: "Drug Lag."

Merck EVP Worldwide Regulatory Affairs & Product Safety Peter Honig used the phrase during his introductory remarks to an Institute of Medicine workshop on drug safety, intended as part of a series of updates on IoM's past review of the US Food & Drug Administration's safety regulation.

Drug lag is a term straight out of the 1980s, when the pharmaceutical industry argued that excessive conservatism by FDA meant plenty of lifesaving drugs came to market first in Europe, while US patients suffered or died waiting for the agency to act. We've since seen analyses claiming the whole notion of a "drug lag" was hooey, but that didn't matter: the perception, as Honig noted, was a key motivating factor in helping push through the Prescription Drug User Fee Act, which undeniably led to a rapid increase in the number of new drugs first marketed in the US.

Indeed, a generation of pharmaceutical industry managers grew up in a world where the industry's largest market (the US) was also its fastest growing market, and the one most likely to grant market entry first. Quite a trifecta.

Well, the US is still the largest pharmaceutical market in the world, but it sure isn't the fastest growing. And Honig, at least, thinks it is also showing signs of lagging behind Europe in market entry. The Merck exec didn't press his case hard, but he did prompt a response from FDA's top new drug review manager, John Jenkins (pictured above).

There are really "two issues people are raising" about new drug reviews, Jenkins noted. One is the undeniable fact that there are some delays associated with new processes and procedures, like the Risk Evaluation & Mitigation Strategies or "safety first" initiative. Jenkins acknowledges that FDA has "taken on a huge process burden" and "the money has not followed at the same pace as the new responsibilities." So some "lag" may be inevitable, at least until resources and habits catch up with the new workflow.

But, Jenkins continued, that isn't really what people worry about. They worry about whether "FDA is becoming more conservative."

And that, Jenkins said, is very hard to quantify, because "we have lagging indicators." Economists, he noted, prefer to focus on leading indicators, but the only was to tell what is happening with approvals is to look at statistics for various application cohorts, and the data inevitably trail months or even years behind the calendar.

So "the most recent data we have is from fiscal 2008, and you really can't see any kind of fall-off or change that is dramatic for first cycle approvals of new molecular entities."

But, to Jenkins' credit, he doesn't just drop the issue there. "It is hard to quantify if my division directors or my office directors are affected by the drug safety debate that has been raging in this country for the last five or six years." The issue "has calmed down a bit recently," Jenkins said, but "have they been impacted?" Are "they less likely to approve a drug today with the same data package that they might have been five years ago?"

"It is impossible to make that assessment because you just can't answer those questions," Jenkins says. "What you have to look at is the data over time to see if you see any trends."

Jenkins noted that he presented an analysis of recent drug approvals last year (at, we might add, our very own FDA/CMS Summit for Biopharma Executives in Washington DC). That data showed seven drugs approved in Europe at that time, but not in the US, and only two in the US but not Europe. (Read our coverage here.) But that data is "now close to a year old. We've been looking at it again, but we haven't reported any more recent analyses." (We hope that will change this Dec. 3, when Jenkins opens the fifth annual FDA/CMS Summit.)

But even a clear indication that there are more drugs approved in Europe first may not be persuasive. "There are a handful of drugs approved in Europe that we haven't approved," Jenkins said. "We'd be happy to argue in public why we didn't approve them, but we can't always do that."

One of those drugs, Sanofi Aventis' weight loss agent Accomplia, was ultimately withdrawn in Europe for safety reasons. So, Jenkins said, "Only time will tell: are we being too conservative and depriving patients of needed drugs, or are they being too aggressive and going to run into the same safey buzz saw that we blew through in the 2000 decade."

Time will tell indeed, but we are impatient here, so why don't you all tell us instead: respond to our poll and let us know what you think. Is there a drug lag? And if there is, is it because FDA is too conservative or EMEA is too reckless? Look for the results next week. (If you are reading via email, click here to take the poll.)


Anonymous said...

As FDA reviewers we are harassed, threatened, and even fired for raising safety issues. This latest is simply a warning to the remaining FDA reviewers. You slow anything down like the last couple we got rid of in 2008 and we'll do the same to you.

There's even e-mails that have made their way to Congress documenting Jenkins intimidating an entire office full of reviewers.

An FDA reviewer

Anonymous said...

Is the government slowing drug approvals due to it's interest in keeping Medicare Part D drug costs down?