A safety review of GSK’s Avandia, under fire and intense scrutiny for its role in the possible development of cardiac adverse effects is nearing completion. In spite of the continued negative press, the pharma company has issued a thirty page rebuttal [PDF] of the Senate Finance Committee’s report alleging those safety issues.

The pharma company faces an uphill battle. In the wake of 24-hour, always on news cycles which seemingly filter only stories of negative sensationalism, it should be taking its damage control cues from Toyota these days.

Among the report’s most “glaring omissions” is its lack of discussion about the final results of the ADOPT, DREAM, or RECORD trials, the company said in a release. It said data from these three trials were reviewed by an FDA advisory committee in 2007 that voted overwhelmingly to keep rosiglitazone on the market.

Perhaps, but the issue now is that GSK chose to keep this information from the meta analysis of these trials from prescribers and patients, according to the Cleveland clinic physician responsible for bringing this data to the forefront. | LINK

• Vanderbilt University (my undergrad alma mater) has announced that it has access to a special blood test that can predict a patient’s risk for heart disease. Using genomic factors, along with the patient’s age, history of stable chest pain, and gender — the assay (dubbed Corus CAD) offers a non-invasive alternative in stratifying coronary disease risk.
  

  The test was developed as a part of a new medical field called genomic medicine, which enables doctors to further personalize patient care based on the unique genomic makeup of individual patients — an important factor for many visiting the doctor. For this reason, the blood test interests many physicians.

  Count me among those interested.

• On a more dour note, there is renewed interest in the recall of rosiglitazone (Avandia), the Glaxo drug with known associations in causing cardiac disease and risk of death; confidential studies via officials in the FDA are recommending the drug’s withdrawal from the market, potentially leaving Pfizer’s pioglitazone (Actos) as the only market alternative in this class to treat diabetes mellitus, type 2.
  

  The company has faced criticism that it has known about the heart-attack risks associated with Avandia for years. Glaxo added a “black-box” warning to Avandia in November 2007 that says the drug can cause or exacerbate congestive heart failure. The company has also faced accusations that it attempted to intimidate scientists and doctors outside the company who raised questions about the safety of Avandia. The company has said that it didn’t try to intimidate anyone.

With the recent story of Vioxx — and its potentially troublesome adverse effects possibly being known to its pharma company before initial launch — hitting the wires yesterday, there is renewed concern of the process by which study results, both public and non-published, be made available for public vetting.

Merck, the pharma company behind Vioxx, has stated that – from study results it commissioned at the time — that its decision to release the drug was based upon sound trial data obtained from carefully analyzed and interpreted information from pooled meta-analyses. Of course, it is now known that these security measures did little to prevent the deaths directly attributed to Vioxx — a problem the FDA has since countered by setting up its own internal resources for analyzing data from meta-analyses.

But, it doesn’t appear to be enough. Some members of Congress are mulling ways of providing drug data transparency, via the FDA, directly to consumers and healthcare providers once a new drug hits the marketplace. Sounds good in theory, but the costs to institute such primary evaluation points for every single new drug application would probably be prohibitive at the very least. | LINK

Is the marketing of a drug online, in particular — on sites like Twitter and blogs like this one (heaven forbid!) — grounds for some sort of special regulatory effort by the FDA? Well, they held a forum for it. While accommodating approx. 350, about 800 signed up.

Participants were asked to consider a number of questions, including how much responsibility drug makers bear for online content about their products and how to determine when online chats about a medicine are influenced by the manufacturer.

This is essentially a non-issue. Policing the entire Internet for critiques and comments about drugs? One might as well impose like sanctions on similarly-themed conversations over cellphones. This is one area where I agree with Pharma. It’s a safe bet that pharma companies constituted the majority of the 800 or so interested in joining the FDA’s discussion — as they have the most at stake. If all of this is all about the “promotion” of drugs or devices via alternative media, then it seems as though more attention should be paid to optimizing the scope  and veracity of traditional media used to represent their products and if those methods promote pharma companies’ wares in a clear and fair manner. | LINK

It’s official. The FDA will NOT withdraw propoxyphene-containing drugs from the market. Known better as Darvon and Darvocet (with acetaminophen), these products stirred controversy when pharma watchdog groups petitioned for their recall, based upon their arguments and spin on adverse effects. The move is probably seen as a relief to pain specialists who routinely give such potent narcotics in their practice. With all of the recent brouhaha surrounding acetaminophen (Tylenol) and its current review, the fear of providers’ livelihood in the medical specialty of pain management has just been abated somewhat.

Kevin, MD has some great reportage on this issue. Essentially, the FDA’s new maxim of transparency and policy change for the benefit of public safety under new leadership has been a clarion call for third parties (mostly watchdogs) that desire greater restrictions to access to certain drugs. Pain agents, currently represented by Tylenol, are just the latest class of drugs in the groups’ crosshairs. Unsurprisingly, a different set of lobbying has emerged in this respect: physicians and pharma companies who have major stakes in their products’ availability. | LINK

• Minnesota man gets prison time for trying to scam one of the state’s largest payers out of medical assistance payments.
• Reform? What reform? Health insurance premiums via employer-sponsored plans to increase next year.
• Andrew Cuomo, NYs’ AG, has completed reform on out-of-network payments to health plans.
• The FDA has approved the sale of Novartis’ Ilaris, the first drug the company has developed as part of its new push to focus on the genetic triggers that cause disease.
• Experts to Congress: Improve the FDA’s medical device approval process.
  

  The House Energy and Commerce Committee, Subcommittee on Health, held a hearing on the regulatory approval process for medical devices Thursday, presumably as preparation for action on H.R. 1346, the Medical Device Safety Act — sponsored by the committee’s chairman, Rep. Frank Pallone (D-NJ). The American Association for Justice certainly regarded the hearing as serving that purpose, specifically citing the legislation in its news release, “Questions about FDA Oversight of Medical Devices Leave Patients Vulnerable.”

The new FDA commissioner, Margaret Hamburg, is taking a page from the Barack Obama playbook: calling for transparency in its functions.

“The FDA has been seen as a cold regulatory agency and also something of a black box,” she said. “We have a chance to open it up and make sure the American people have the safe, high-quality foods they need, the safe and high-quality drugs and medical equipment they need.”

Hasn’t the gov’t agency always done that? If it’s anything that has been regulated in recent years, it’s the maintenance of the rapid rate of New Drug Application turnover and patent extention approvals of rather mundane and redundant formulations of top selling medications. | LINK

I remember the cyanide-laced Tylenol scare back when I was in high school. Although this post has nothing to do with that story, it was the first thing that came to mind as as I saw this:

Advisers to the U.S. Food and Drug Administration will meet late next month to review a new agency report that calls for stronger warnings, better consumer education, and limits on doses for both prescription acetaminophen and over-the-counter (OTC) acetaminophen, best known as Tylenol. [...] Severe liver damage can result from a lack of consumer awareness that acetaminophen can cause such injury. Also, many people may take more than the recommended dose of over-the-counter pain relievers in the mistaken belief that taking more will be more effective against pain without posing significant health risks.

So, although the gist of this post has nothing to do with the musings of a mass-murderer, it does represent what the agency is trying to accomplish in the new Obama administration: transparency of its regulatory bodies which, in part, govern healthcare deliery in this country. | LINK

The FDA is drafting guidelines for medical device and drug makers concerning the portrayal of information on advertisements about their products. What’s interesting about this move is that, in addition to the usual information regarding the use of outright bogus claims as a violation of FDA rules, the agency also advises against the use of stubtle advertising techniques which may portray a drug or device as wholly benign amid known adverse effects and rigorous monitoring schedules — a practice they say is “deceptive” and “discordant”. | PDF LINK

In the march toward his overall healthcare reform plan, President Obama has reversed a George W. Bush administration regulation that gave the feds the ability to trump state governments’ decisions concerning liability with medical devices. Device makers were essentially shielded from healthcare consumer lawsuits Bush generally deemed as “frivolous” in nature. Also, Big Pharma was helped by such actions since the FDA often did not follow regulatory guidelines in implementing new drug indications.

Obama in a two-page memo wrote that federal agencies and departments could claim state law is pre-empted by federal law only when there is a well-defined legal basis. The memo stated that state laws are important because they supplement federal regulations. “State and local governments have frequently protected health, safety and environment more aggressively than has the national government,” Obama wrote.

If efforts at stopping government pre-emption give the patient more of an incentive in trusting public delivery of healthcare, at the same time cutting massive bureaucratic waste from lack of government regulation in healthcare delivery, this effort of Obama’s is to be praised. On the contrary, concerns over a flurry of patient lawsuits from Republicans should be a nonissue since Obama acknowledges the rights of individual states in this case. | LINK

“What exactly ails you today? Well, whatever it is, I got your cure. Right here. Yep, my all purpose tonic. Cures what ever you’ve got.”^[1]

Such admonitions of instant health remind me of those charming 19th century period pieces in which a hack shaman toils about the Wild West searching for some sucker to take him up on his offer to be free of every illness once and for all. Of course, the story ends with the unfortunate “patient” a few bucks poorer and purveyor of the dubious claim laughing all the way to the bank. 

This scenario also comes to mind given the recent events surrounding General Mills (based here in MN), the makers of Cheerios. The FDA is launching an all out PR campaign against the company, alleging false claims on its box of oats. Citing claims of an “seriously inappropriate” nature, the FDA warns that the cereal’s boast of the ability to lower one’s “cholesterol by 4 per cent” constitutes that of the nature of drugs awaiting approval by that body — in essence, becoming a pharmacologic agent in the process. The FDA is giving General Mills 15 days to come up with a reason for the promotion of the claim. 

And in (possibly) related news, General Mills stock rose $.74 yesterday. | LINK

1. The inspiration for this post comes from the video for “Say Say Say” (#1, 1983) by Michael Jackson & Paul McCartney. [↩]

This has to be the absolute sanest thing the FDA has done in quite a while: reject a drug (for an indication to treat depression) which appears in the same class as drugs used to treat acute psychosis and chronic schizophrenia (!)

A committee of Food and Drug Administration advisers said Seroquel XR was safe enough for treating some patients with depression but opposed use of the drug for fighting anxiety given the serious side effects.

The panel voted 6-3 that Seroquel XR had acceptable risks if it was added to other medicines to find a workable combination to alleviate depression. Several panel members stressed that doctors should try other treatments for depression first before deciding to add Seroquel XR.

Okay, so the FDA’s stance was not exactly prohibitive on the use of Seroquel to treat depressed mood; it was more conciliatory (almost as if its pharma company requested it)…

The panel split 4-4, with one abstention, when asked if it was safe enough to use Seroquel XR as the only treatment for depression in some cases. Panelists said there were safer medicines that should be tried if only one medicine was going to be used.

Does that mean that physicians **won’t** prescribe it for depression as a first-line? Heck, they already give the stuff for sleep. | LINK

At the dusk of the first decade of the 21st century, a new FDA emerges — one that, shaped by the new Obama administration, will strive to ethically approve drugs and devices while considering every possible significant adverse risk to the general public. Call it a lesson learned from putting the politics of fast-tracking at the hands of major third parties, namely Pharma, ahead of patient and public safety.

This notion is all too cognizant in the minds of the FDA panel, which is struggling with the approval of a new anti-diabetic drug (similar in function to this agent) which shows even greater promise as an adjunct in the early stages of treatment of the disorder. The problem? During the early phases of the drug’s R&D, the incidence of a certain type of thyroid tumor began to show up in rats. Consequently, the FDA is “seeking additional clinical data” (since rats aren’t exactly people). It’s certainly a prudent move, especially in a weak healthcare economy overall, in which the process of new drug development is occurring at a snail’s pace — a rate at which a new approval’s faults would invite extreme immediate  and well deserved post-market scrutiny. | LINK