Envisioning 2.0

The Food and Drug Administration (FDA) announced today that it would be working with Barr Pharmaceuticals to “resolve the remaining policy issues associated with the marketing of [the contraceptive] Plan B as an over-the-counter [OTC] option” after months of delay.

Some think that this move smacks of opportunism. The FDA made this announcement a day before the confirmation hearings of Dr. Andrew von Eschenbach. Some members of Congress have vowed to block a floor vote on his nomination unless the agency makes a decison on the fate of Plan B.

This announcement is good news, but is a poor communications strategy. Its timing looks fishy and reactionary. The agency had months to move the Plan B OTC application forward and decides to do so now? I’m not sure if this announcement answers a lot of questions. In fact, it raises several more and may make Dr. von Eschenbach’s hearings even more contentious.

For more on this story, please see this article from the New York Times.

The blog, Eye On FDA has a good analysis of the FDA’s announcement.

Is the FDA moving to head off federal legislation that may more tightly regulate how the FDA manages membership on its advisory boards?  This may be the motivation behind a recent announcement that the FDA is drafting new rules governing how it will exclude scientists with ties to industry from the panels that help it decide whether to approve medications.

The new FDA guidance will virtually ban any physician that has participated in a marketing campaign for a pharmaceutical company from participating on its advisory boards.  Scientists that have received support through an academic institution will be granted waivers.

See this New York Times article for more.

An article appearing in today’s New York Times reveals that FDA officials waged an internal battle over the approval of the antibiotic Ketek.  Senator Charles Grassley, a critic of the FDA’s relationship with the pharmaceutical industry, said the conflict indicates that the FDA has “made it their business to discredit Dr. Graham and others who aren’t willing to cater to the drug companies.”

I will touch on the issue of antibiotic drug safety in the next installment of my ongoing series: “The FDA and the Pharmaceutical Industry.”

The New York Times reports today that senators Michael B. Enzi and Edward M. Kennedy of Massachusetts are developing legislation that would impact how drug companies report clinical trial data and monitor drug safety.  The senators are being very coy about the details of the new legislation, which may be presented to Congress after the election season.  Click here to read more (registration required).

This article is part of an ongoing series on this blog titled: “The FDA and the Pharmaceutical Industry.” Click here to read other posts in this series.

The Food and Drug Administration (FDA) is currently a very bruised, battered and bewildered agency. A recent Harris Interactive/Wall Street Journal poll indicates that the public is loosing confidence that the FDA has the ability to ensure the safety and efficacy of prescription medications. Consumer advocates are saying that the FDA is doing too little to remove unapproved drugs from the market. To make matters worse, the agency is facing increased scrutiny over how it handled a recently halted clinical trial testing the antibiotic Ketek in children. (At issue is the appropriateness of using non-inferiority rather than placebo-controlled clinical trials to approve antibiotics. For more on this topic, see this post.)

The FDA is not without its defenders. Robert Goldberg, PhD of the Center For Medicine in the Public Interest and co-author of the blog Drug Wonks, has regularly taken critics of the FDA to task on a range of issues, including clinical trial design and drug safety. (See this recent post on Senate Finance Committee Chairman Chuck Grassley’s oversight of the agency.)

So, is the FDA a paper tiger, or an overzealous regulator? Let’s take a look at both sides of the issue.
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Jerry Avorn, MD takes stock of drug approval and side effect dectection in a post-Vioxx world.  He thinks that some observers have drawn some incorrect lessons from recent drug withdrawals.  Click here to read his commentary, published in Circulation.

I’ve been thinking a lot about the relationship between the pharmaceutical industry and the Food and Drug Administration recently. Because of this, I’ve decided to author a series of periodic posts to explore this issue and solicit comments from readers on this subject. With this post, I’m creating a new category on this blog, called “FDA and the Pharmaceutical Industry,” and will file articles on these topics under this heading.

The Issue: Non-inferiority vs. Symptom Resolution in Antibiotic Clinical Trials

I attended an interesting talk this week given by Dr. John Powers of the Food and Drug Administration focusing on the development of antimicrobial medications. He pointed out a number of interesting facts about the growing rate of bacterial resistance to antibiotic medications, the lack of new drug development and the need for improved clinical trials. He noted that his talk does not represent the views of the Food and Drug Administration. (Powers delivered his lecture at the CDC’s annual Get Smart: Know When Antibiotics Work conference.)

Over the years I’ve noticed that a common theme of presentations delivered by FDA officials is the design of pharmaceutical industry clinical trials. Powers’ lecture was no exception. He pointed out that manufacturers making new antibiotics must demonstrate that their medications are non-inferior to currently available antimicrobials. For example, a drug maker developing a new macrolide antibiotic (i.e., drugs like Zithromax) does not have to show that it works better than other drugs in the same class.

Powers argued that non-inferiority is an inappropriate criterion for evaluating new antibiotics. Instead, he suggested that pharmaceutical companies should be required to demonstrate that their drug is superior to other medications on the market, specifically when it comes to symptom resolution. This means that a new macrolide would have to reduce the symptoms of a bacterial infections faster than similar medications.

Pharma’s Reaction

After hearing Powers’ presentation, I spoke with a few people I know from the pharmaceutical industry to gauge their reaction to this suggestion. They said:

• Superiority Is Difficult To Prove: They noted that it would be nice to show that an antibiotic positively impacts symptom resolution. However, this type of trial would be difficult to design and mount, particularly because symptom resolution is hard to measure. (I wonder if there are any validated and well-accepted instruments that investigators use to determine how well a drug reduces the symptoms of an infection.)

• The FDA Suggests But Does Not Require Changes In Trial Design: Non-inferiority trials have been the standard of antibiotic study design for decades. Companies might feel more compelled to change the design of antibiotic clinical trials if the FDA required it. However, the FDA has not done so. Companies are unlikely to make major shifts without specific guidance from the FDA about what protocols will be accepted, which instruments are valid and how advisory boards will evaluate data from these studies.

In Summary . . .

Clearly, clinical trial design can and should be improved. However, changes are unlikely to occur if the FDA does not require them. In addition, the FDA would have to work closely with industry on protocol design, as it already does. Finally, in the case of symptom resolution, the FDA would have to help develop validated and acceptable measures.

It will be interesting to see whether and how the FDA adopts Powers’ recommendations.

Next Up: The FDA: Paper Tiger Or Overzealous Regulator?