What's Wrong with the FDA?

The author of this post on the Masters in Health Care blog approached me seeking a cross-listing, and the topic seemed pertinent enough for this blog to me to oblige:
http://www.mastersinhealthcare.com/blog/2011/15-disturbing-facts-about-the-fda/

Now, a few comments. Several of these complaints seem to me to be right-on. Others seem somewhat ambiguous or even contradictory. For example, the writer seems disturbed both that the FDA might be too quick to act to protect the public safety (risking ruining the reputation of an industry that later turns out blameless) and also too slow in taking action to protect the public. My main question for the writer would be: the Obama administration put new leadership in place at the FDA, and we know the old adage about turning around either an ocean liner or else a Federal bureaucracy. Is there any evidence that any change for the better is occurring as a result? Or is it same ol', same ol', assuming enough time has passed to judge?

Are We Seeing the New FDA Emerge?

According to a New York Times editorial--
http://www.nytimes.com/2010/05/05/opinion/05wed3.html

--there may be positive changes in the air at the FDA, consistent with the more-hard-nosed team that the Obama administration had appointed to replace the generally pro-business folks of the previous regime. According to the Times:

• The percentage of members of advisory boards granted waivers due to conflicts of interest has been reduced from 15 to 5 since 2007
• Commissioner Margaret Hamburg has issued a letter to staff that any future proposed waivers have to be justified by descriptions of how hard the staff worked to try to find a neutral expert first
• FDA will now release the name of the company involved in the conflict, and a rough dollar amount of the conflict, if a waiver is granted, as part of increased disclosure

The Times continues to hope that there will be less need for disclosure and no conflicts of interest, but also agrees these are all positive steps.

You Heard It From the Top: FDA Can't Function

As a rule there is an infallible way of committing suicide as an agency chief in the executive branch of the US government. Just go testify before Congress that your budget is inadequate, when the budget has been determined not by Congress but by the White House. To do so is to tell Congress that your boss is a moron.

On the other hand, if the boss is a lame duck with a popularity rating far down in the toilet, what do you have to lose?

The first agency head to ventilate in this fashion was FBI head Robert Mueller. Now, FDA director Andrew von Eschenbach has joined in.

Depending on who he was talking to, von Eschenbach put a little smiley face or frowney face on his comments. One version was that the agency simply lacked the funding needed to carry out its mission. Then the gussied-up version was that the agency is OK for now but cannot maintain its edge in the future.

But the basic story is that you heard it right from the top--the FDA cannot assure the public reasonable safety in its food or drug supply because the budget requested by the White House is insufficient. In a climate when Reps and Dems apparently cannot agree on anything, there was bipartisan support in the Senate Appropriations subcommittee for increasing the budget of the FDA.

Harris G. Panel's bipartisan view: F.D.A. is underfinanced. New York Times, April 16, 2008; http://www.nytimes.com/2008/04/16/washington/16fda.html?_r=1&scp=1&sq=gardiner+harris+panel%27s+bipartisan+view+f.d.a.&st=nyt&oref=slogin

FDA Compromise Bill Passes: Adding Up the Score

The House passed by a 405-7 vote on Wednesday, 9/19 a compromise measure to extend the FDA's Prescription Drug User Fee Act (PDUFA) by another 5 years. The Senate followed suit the next day and it was anticipated that the bill would quickly be signed by the President, in time to prevent the FDA from having to issue pink slips to 2000 employees as time runs out on the old PDUFA arrangement.

The compromise bill contains several important measures, and some provisions that remind us about the adage of not wanting to watch either sausage or legislation being made. Here's a quick run-down from my point of view:

Good News

• The FDA has increased authority to require companies to do post-marketing safety studies, and impose fines on companies that do not comply. In the past, the vast majority of these requested safety studies were never completed, and the FDA had only the blunt instrument of withdrawing the drug from the market as a method of enforcement.
• The FDA will for the first time have a computerized safety monitoring system utilizing insurance and pharmacy claims data. The existing system depends solely on voluntary reporting of side effects and drug reactions and is estimated to miss 90% of such events.
• The House eliminated some Senate provisions that would have protected drug companies from liability suits. Under the compromise version it is harder for a drug company to argue in court that since the FDA approved the drug and its labeling, the company has no liability if the drug ends up killing people.
• The FDA can actually force companies to alter labels rather than always having to ask nicely.
• Companies are required to post results of all clinical trials of approved drugs on a public, searchable website.
• The FDA gains some new powers to better police deceptive advertising.

Bad News

• The basic PDUFA mechanism remains in place. The industry, not the U.S. public, provides the lion's share of the funds that the FDA uses for the drug approval and safety monitoring process. This perpetuates the basic flaw that FDA critics argue has been the result of PDUFA--that the FDA inevitably sees the industry as its client, rather than seeing its overriding duty as protecting the public health.
• Conflict of interest waivers, allowing scientists with financial ties to the industry to participate in FDA advisory panels despite the rules that supposedly ban such participation, was a particular political football. The Senate version wanted no limits on waivers; the House wanted only one waiver per meeting. (I would vote for none.) The compromise result is delightfully Byzantine. The FDA should count how many waivers it granted in the 2007 fiscal year and reduce the number granted by 5% per year in each of the following 5 years. Congress--ya gotta love 'em.
• The pediatric trials scam continues. For initially excellent motives, Congress agreed that if a company tested its drugs in kids, they would get a 6 month patent extension in exchange. It turned out in practice that the cost of the research in kids was substantially less than the profits made from the 6 month extension, leading to major abuses where drugs that would never be used in kids were tested in kids anyway just to get the extension. The Senate had reasonably wanted to reduce this extension to 3 months; but the compromise version keeps it at 6 months.
• Stronger powers to regulate drug ads, especially a moratorium on direct-to-consumer ads for new drugs, were beaten down by intense lobbying by the media and advertising industries, which clearly don't want to see the DTC-ad cash cow dry up.

Harris G. House passes bill giving more power to the F.D.A. New York Times, Sept. 20, 2007.

Kaiser Daily Health Policy Report. House approves prescription drug user fee act reauthorization. http://www.kaisernetwork.org/daily_reports/rep_hpolicy_recent_rep.cfm?dr_cat=3&show=yes&dr_DateTime=20-Sep-07#47641

Wilde Mathews A, Kang S. Media industry helped drug firms fight ad restraints. Wall Street Journal, Sept. 21, 2007; page B1.

Avorn: Give FDA Committees Some Credit

People like me tend to think badly of the FDA's recent track record. The FDA funding bill now in House-Senate conference committee perpetuates the system of allowing industry user fees to fund much of the drug review process, making the agency more beholden to the industry. The Senators who shepherded the bipartisan compromise bill through, Kennedy and Enzi, seem to have bought into the line of bunkum that if the FDA advisory committees were actually required to exclude those who had financial conflicts of interest, there would be no "experts" left to fill the committee slots.

Dr. Jerry Avorn of Harvard, author of Powerful Medicines and a well-known critic of the pharmaceutical industry and regulatory system, writes in this week's New England Journal that it is not as bad as all that. He reviews several recent decisions from FDA scientific advisory committees that show considerable backbone in standing up for drug safety and protecting the U.S. public. He compares the recent drug action to an action on a similar drug within the past decade, and shows that for the drugs Arcoxia (anti-inflammatory) and rimonabant (weight loss), the recent decision was much more scientifically defensible and hard-nosed than was the previous one. The one disappointment he admits to is Avandia, noting that its advantages as a drug for diabetes are so meager that it is hardly defensible to keep it on the market in light of fears of increased heart risks.

Avorn has basically given up on the FDA or Congress cleaning up its own messes and so calls on the scientists who serve on the external advisory committes to shoulder the burden of standing up for the facts. He reminds us that when we compare the regulation of the drug industry with the energy, defense and finance sectors, we have it head and shoulders above them in our ability to bring rationality and science to bear on the problems, even with our present flawed system.

Avorn J. Keeping science on top in drug evaluation [perspective]. New England Journal of Medicine 357:633-35, Aug. 16, 2007.

FDA Funding and Drug Safety: New Report from GWU

When I first downloaded this report from the Rapid Public Health Policy Response Project at George Washington University in DC, I was taken aback to see the Pfizer logo on the first page; but the content, though partly supported by Pfizer's "Public Health and Policy Group," seems reasonably balanced.

The report summarizes existing law on the Prescription Drug User Fee Act (PDUFA) and the current debate over whether this law promotes adequate attention to drug safety, as opposed merely to speedier approval reviews to keep the industry happy.

In HOOKED, I argue that PDUFA should be repealed and the FDA supported fully from congressional appropriations, not industry user fees. So I was pleased to read in the report the line-up of those who argue that this is the case:

Four former FDA commissioners
The Institute of Medicine report on the FDA
Consumer groups
Twenty-two experts in drug safety and regulation, including 3 former editors of the New England Journal

The report can be obtained at:
http://www.gwumc.edu/sphhs/about/rapidresponse/download/RapidResponse_PDUFA.pdf