Following up on last week’s blog discussing the FDA hearing underway to determine the safety of the prescription diabetes drug, Avandia, the FDA advisory review panel concluded a two-day hearing last Wednesday by recommending 20 to 12 that Avandia remain on the market with label revisions and other restrictions. This deeply divided panel included 17 votes to add warnings or restrictions on the drug, and 12 votes to remove the drug from the market.

The members voting for Avandia’s removal said the drug “has no unique benefits and therefore the benefits of the drug do not outweigh the risks.” They also pointed out that Avandia’s primary competitor, Actos, is an acceptable alternative to Avandia and therefore there is no therapeutic necessity to keep Avandia on the market.

Even the use of Actos has been called into question. Harvard researchers based at the Independent Drug Information Service (, note that “in mid-2007 the FDA added black-box warnings cautioning that both rosiglitazone (Avandia) and pioglitazone (Actos) increase the risk of congestive heart failure.” These safety concerns, “along with an increased risk of fracture, have greatly dampened enthusiasm for use of both of these drugs.”

The ultimate fate of Avandia now rests in the hands of the FDA who stated that they “took the panel’s advice seriously and that [the FDA] would consider its regulatory options.” If the proposed additional warnings and restrictions are implemented, scientist Steve Nissen, who published the first study documenting the cardiac risks of Avandia in 2007, estimates that 95 percent of Avandia’s use will end. “Effectively, this drug is gone.”

Interestingly, the committee also recommended by a vote of 19-11 that the trial currently underway comparing Avandia to its rival Actos be continued, though at least one member questioned the ethics of this, given the potential risks.

Litigation yields access to studies, helps expose risks

Litigation plays a valuable role in exposing industry schemes to withhold safety data. For instance, GSK’s earlier suppression of studies showing risks associated with the drug Paxil lead to litigation and settlements that required GSK to post information on-line about all their clinical trials. It was this posted information that Nissen and fellow researcher Kathy Wolski of the Cleveland Clinic used to perform their 2007 analysis of over 40 studies that showed that Avandia raised the risk of heart attack, stroke and death in comparison to Actos.

Another example of the benefit of litigation is seen by the PAL-member class action lawsuit concerning the drug Zyprexa whichyielded hundreds of documents, some of which revealed Eli Lilly’s own internal studies documenting the increased risks that Zyprexa posed as a treatment for dementia in elderly patients.

New evidence, studies bring risks to light

Ongoing investigations by Senator Grassley and almost a dozen new studies documenting the risks of Avandia have kept the issue alive, prompting the FDA’s ongoing review, including last week’s hearing.

One comparative effectiveness study by David Graham of the FDA was published this past June. Graham worked with researchers at the Centers for Medicare and Medicaid Services to collect records from nearly a quarter million Medicare recipients.  Elderly diabetics, who used Avandia instead of its competitor, Actos, had a 68 percent increase in the risk of heart attack, stroke, heart failure or death. Graham stated:

“We estimate that about 48,000 excess cases of [heart attack], stroke, heart failure, or death were attributable to the use of [Avandia] rather than [Actos] from 1999-2009.”
Graham additionally stated “the RECORD study would have been dismissed as ’garbage’ if it had been used to seek the drug’s original approval.”

What’s next?

The question of whether the FDA will allow Avandia to remain on the market is still up in the air.  Beyond that, what else can we do to stop such illegal and hazardous industry behavior—the same behavior that resulted in the Vioxx tragedy, which lead to up to 60,000 deaths? As litigation and other sources have revealed suppression of drug risks concerning Vioxx, Paxil, Celexa, Zyprexa, and many other drugs, the problem seems endemic.

To begin to address this problem, the FDA needs the resources and authority to examine all relevant clinical studies for data-tampering. Government and private consumer lawsuits must continue, including possible criminal prosecution. Finally, we should all remember that what you read on your drug label or hear in a TV ad may not be the whole story. Skepticism is warranted and further regulation is critical to all of us–we need medical care we can trust.