FDA's Real Risk Communication Challenge

FDA is the first to admit that it hasn’t quite figured out the best way to communicate drug risks to patients—especially how to convey emerging risk information without scaring patients away from a helpful or life-saving treatment.

But it is also clear that FDA hasn’t quite figured out how to communicate within the agency on communicating risk to patients, either.

On Friday, FDA announced a major new policy on risk communication under which it will begin alerting the public to potential safety problems with a drug or biologic at the very beginning of the post-marketing drug safety process. (Check here for our earlier take on that initiative.)

On Monday, FDA’s senior advisor on risk communication in the Office of the Commissioner, Nancy Ostrove, spoke at the Food & Drug Law Institute’s annual meeting on advertising and promotion.

Given that the title of Ostrove’s speech was “FDA’s Initiatives in Communicating Risk Information,” it appeared to be the perfect venue for discussing the new program—so much so that one might have wondered whether the agency timed the announcement to coincide with Ostrove’s FDLI presentation.

Apparently not.

After avoiding mention of the program in her opening remarks, Ostrove gave the following disclaimer before the question and answer session: “I can tell you one thing I am not going to talk about…the press release that went out on Friday concerning the FDAAA provisions on quarterly reports. I didn’t even get it until today. So I can’t talk about it.”

Given the pains that FDA took in announcing the decision—a rare embargoed media call ahead of the official announcement with Office of Drug Safety director Gerald Dal Pan and Safety Policy & Communication associate director Paul Seligman—it was surprising that Ostrove wasn’t on the call herself, or, at the very least, aware that it had taken place.

There may be good reasons for Ostrove not to have been in on that decision. But given FDA’s recent focus on risk communication (check out our coverage in The RPM Report here and here), we can’t help but wonder whether the real communication on risk needs to first take place at FDA.

image from flickr user rubatacchini used under a creative commons license

Celgene and FDA’s New Drug Safety List

It’s over for Celgene. That’s it. Revlimid’s done. Investors should evacuate the premises immediately.

After all, a vital cog in Celgene’s cancer portfolio is on FDA’s first quarterly drug safety posting.

Sound too alarmist? Maybe a little extreme? Of course it is. But that’s how a good number of investors reacted to the posting.

Celgene lost about 3% of its value in the two days following the announcement. Not terrible. But if you look at trading the day of the announcement, volume more than tripled and the stock dropped 6% of its value in midday trading with a low of $63.00 per share before edging back up.

We’ve seen that investors and drug companies are finding it challenging to communicate and interpret risk, respectively. To read our take, click here.

FDA threw a new twist into the risk communication equation last week. In response to a specific provision in the FDA Amendments Act, the agency will be posting a list of drugs every three months that officials deem worthy of further risk evaluation following voluntary adverse event reports from patients and health providers. So for all of the FDA critics out there, this is something the agency had to do.

In a September 5 press release announcing the initiative, FDA tried to be as unalarmist as possible. “My message to patients is this: Don’t stop taking your medicine. If your doctor has prescribed a drug that appears on this list, you should continue taking it unless your doctor advises you differently,” said Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research.

The agency was very explicit about what a drug showing up on the list actually means for that drug:

“The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk, or that FDA has identified a causal relationship between the drug and the listed risk. It is on the list only because FDA has identified a potential safety issue.”

In a media briefing prior to the official announcement, Office of Surveillance and Epidemiology director Gerald Dal Pan explained that a listing on quarterly report means FDA has begun an analysis of whether the drug needs further evaluation such as further information, clinical trials, epidemiologic study, need to conduct an epidemiologic study, and possibly the need to conduct a clinical study.

CDER associate director for Safety Policy and Communication Paul Seligman said two things have to happen to get on the quarterly list: first, a provider submits an AER report to FDA’s voluntary AERS reporting system. Second, our FDA staff have judged that further follow up or review is warranted.

Seligman highlighted that the work FDA is doing to support the quarterly list isn’t anything new. “This is work we’ve been doing for decades.” What’s new is, he says, FDA is telling the public what it’s working on in postmarket surveillance at the “earliest stage.”

FDA’s new initiative is not without some irony. The first quarterly report, which is supposed to represent FDA’s work at the “earliest stage” is for January 2008-March 2008, not the just passed April 2008-June 2008 quarter. That is understandable since FDA has a seemingly limitless number of FDAAA provisions to implement and a very limited number of resources to get it done. We’re just pointing it out. There were similar issues with FDA’s “early communication” initiative, which appeared to be anything but early. To read more, click here (also one of our favorite blogs and blog pictures.)

Here’s the first list of 20 drugs on the quarterly post:

Potential Signals of Serious Risks/New Safety Information Identified by the Adverse Event Reporting System (AERS) January - March 2008

Product Name: Active Ingredient (Trade) or Product Class	Potential Signal of Serious Risk/New Safety Information
Arginine Hydrochloride Injection (R-Gene 10)	Pediatric overdose due to labeling / packaging confusion
Desflurane (Suprane)	Cardiac arrest
Duloxetine (Cymbalta)	Urinary retention
Etravirine (Intelence)	Hemarthrosis
Fluorouracil Cream (Carac) and Ketoconazole Cream (Kuric)	Adverse events due to name confusion
Heparin	Anaphylactic-type reactions
Icodextrin (Extraneal)	Hypoglycemia
Insulin U-500 (Humulin R)	Dosing confusion
Ivermectin (Stromectol) and Warfarin	Drug interaction
Lapatinib (Tykerb)	Hepatotoxicity
Lenalidomide (Revlimid)	Stevens Johnson Syndrome
Natalizumab (Tysabri)	Skin melanomas
Nitroglycerin (Nitrostat)	Overdose due to labeling confusion
Octreotide Acetate Depot (Sandostatin LAR)	Ileus
Oxycodone Hydrochloride Controlled-Release (Oxycontin)	Drug misuse, abuse and overdose
Perflutren Lipid Microsphere (Definity)	Cardiopulmonary reactions
Phenytoin Injection (Dilantin)	Purple Glove Syndrome
Quetiapine (Seroquel)	Overdose due to sample pack labeling confusion
Telbivudine (Tyzeka)	Peripheral neuropathy
Tumor Necrosis Factor (TNF) Blockers	Cancers in children and young adults

That’s it. That’s all you get. No numbers of reports and no nature of the seriousness of the adverse events reported.

So back to Revlimid. The drug was associated with reports of the serious skin rash Stevens Johnson Syndrome. As you may recall, SJS was the reason the COX-2 inhibitor Bextra was taken off the market.

We’re not doctors (we don't even play them on TV), but two observations which should quell any investor jitters based on the very little we know so far.

First, if you’re taking Revlimid, a drug used for MDS and multiple myeloma, the potential for SJS is likely the least of your concerns. Second, Revlimid carries one of the most comprehensive, thorough risk management plans (RevAssist) of any drug on the market managed by a company that revolutionized the efficacy of risk management plans for thalidomide, arguably the most dangerous drug ever marketed. If there are more cases, FDA can rest assured RevAssist will catch them.

So what do you think? Is this quarterly list a good idea or a bad one? Are we getting in too deep and too early when it comes to FDA’s postmarket responsibilities? Per usual, we’d love to hear your take.