Last week, the American College of Physicians (ACP), a 129,000-member group of internal medicine physicians, and second-largest doctors group in the US, called for increased FDA authority and  funding to help protect  consumers from the risks of newly-approved prescription drugs.  Their six recommendations were:

1) increased funding for FDA staff and technological capability to keep pace with the increased workload due to the number and scientific complexity of new products submitted for pre-approval, globalization, and emerging safety challenges.

2) increased FDA authority and capacity to regulate drugs manufactured outside the US;

3) expanded FDA authority and involvement in the design of clinical trials to better evaluate safety and efficacy, through longer trials with larger, more representative target populations;

4) a ban on clinical studies of ‘bundled’ drug products that reduce access to drugs;

5) Improvements that increase  reporting of adverse events by doctors and others; and

6) limits on direct-to-consumer advertising in the first 2 years a drug is on the market.  

Increased FDA funding:

The ACP report notes that FDA’s “ability to approve and monitor new drugs has been compromised by chronic underfunding, limited regulatory authority, and insufficient organizational structure.” ACP recommends that FDA funding is increased, to improve their “ability to approve and monitor prescription drugs….”

 Regulating drug manufacturing overseas:

The ACP should be praised for bringing attention to severe under resourcing at FDA, particularly as it affects the Agency’s ability to ensure the safety of drugs manufactured overseas. Today’s globalized pharmaceutical supply chain has rapidly outgrown FDAs capacity, and FDA is not able to inspect foreign sites with any meaningful frequency. A 2008 GAO study found it would take FDA 13 years to inspect each foreign manufacturing establishment once, while domestic sites are inspected on average every 2.7 years.

 ACP points out that a provision for increased foreign inspections were included in a bill (H.R.759) introduced by Reps. Dingell, Pallone and Stupak in January this year. A similar bill (S.882) championed by the late Senator Kennedy and Senator Grassley also seeks to increase foreign site inspections by FDA. Both bills establish new industry user fees to pay for this expanded oversight, but also require annual increases in other appropriations to ensure sustainability. ACP importantly indicates that both types of financial support are needed, and mentions a number of other key provisions in the House bill, including a requirement for dedicated foreign inspection staff.

Facilitating increased physician reporting of adverse events:

The ACP also recommends FDA pursue efforts to “educate physicians on how and when to report an event that is potentially drug-related.” They also proposed streamlining the reporting systems and ensuring anonymity to “facilitate reporting by health professionals.”

DTC advertising of new drugs:

The report acknowledges that direct-to-consumer (DTC) advertising can “dramatically increase [use] of a new drug and … may expose large numbers of people to a drug with undocumented safety concerns.”

The best example of this concerns was seen in the  rapid use of the  pain-killer Vioxx upon hitting the market. The aggressive DTC advertising and other promotional activities  by manufacturer Merck lead to Vioxx’s use by over 20 million consumers, which then lead to  88,000-139,000 cardiac events, and  an estimated 35,000-55,000 deaths.  Adverse reactions and safety concerns arose with the  drugs Zyprexa and Bextra, among many others 

To address this concern, ACP recommended that FDA ‘limit’ the DTC advertising of newly approved prescription drugs, and require that labels and ads indicate that data related to the new drug’s “risks and benefits … are less extensive than those [for older] products…”

 Prohibiting clinical trials of ‘bundled’ products:

In addition, ACP also makes a recommendation that would help FDA avoid placing itself in the position of helping drug manufacturers introduce ‘bundled’ or combination drug products designed to protect a drug from generic competitors. 

For example, the report describes how, in 2005, the drug manufacturer “Pfizer submitted plans to the FDA to begin conducting large trials to test the cholesterol drug torcetrapib in combination with the popular and widely used statin Lipitor.”  By allowing clinical trials of the ‘combination drug’ rather than just torcetrapib alone, approval of the new combination drug product would insulate Lipitor from competition. This then puts FDA, in approving the study design, in the awkward position of helping the drug manufacturer avoid anti-trust prohibitions, the report said.

This concern is similar to the claims in the PAL member lawsuit on the drug Norvir, where drug manufacturer Abbott Labs bundle their HIV protease inhibitor cocktail drug Norvir in a new bundled-product-drug Kaletra, in order to increase market share.

ACP recommends that FDA not approve clinical trials which seem to be designed to ‘bundle’ a new drug with an existing brand name drug, and thus perpetuate the patent-protected sales of the new combination product.

To read the full report, visit http://www.acponline.org/advocacy/where_we_stand/policy/fda.pdf

Largest criminal fine imposed by US in any matter   

Last week, the Department of Justice (DOJ) announced that its investigaton and several whistle-blower, or qui tam lawsuits had lead to a $2.3 billion dollar settlement resolving the alleged criminal and fraudulent marketing and promotion of the drug Bextra by Pfizer (NYSE: PFE), as well as their illegal promotions of 12 other drugs.  The settlement included $1.2 billion criminal fine for the felony promotion of Bextra, the largest ever imposed by the US for any matter.

 
The lawsuits were brought in response to the  regarding various civil and criminal charges connected to the fraudulent marketing and the payment of kickbacks. The settlement includes a guilty plea and a civil settlement of $1 billion, with $668 Million for federal programs, and the remainder going to reimburse States Medicaid costs.

What did Pfizer do?  

While the exact terms of the guilty plea are not available yet, it is alleged that Pfizer committed a felony by ‘misbranding’ the drug Bextra, or promoting its sale and use for treatments and at dosages above the maximum levels approved by FDA. (Bextra was approved by the FDA to treat symptoms associated with osteoarthritis, rheumatoid arthritis and primary dysmenorrheal. While a doctor can prescribe a drug for any use, a drug manufacturer may not promote any use other than that which has been approved by FDA.)  The settlement agreement describes the DOJ allegations that Pfizer acted illegally by:

• Making false and misleading claims of safety and efficacy of Bextra in sales materials and sales messages;
• Promoting Bextra directly to physicians, using  payments disguised as so-called advisory boards, consultant meetings, or  travel to lavish resorts;
• Creating sham requests in order to send unsolicited information to physicians about unapproved uses and dosages;
• Sponsoring  purportedly independent continuing medical education programs (“CME”) to disseminate specific messages about unapproved uses of Bextra;
• Promoting Bextra for unapproved uses and dosages by initiating, funding and sometimes ghostwriting scientific articles about Bextra for unapproved uses, without appropriate disclosure of Pfizer’s role in preparing the article, and;
• Providing  promotional samples and otherwise promoting Bextra for unapproved uses and dosages to surgeons and other medical prescribers who had no FDA-approved use for the Bextra samples, or at that dosage;

But wait, there’s more: Pfizer’s off-label promotion and deceptive marketing of twelve other drugs

The settlement also releases other claims related to the DOJ’s allegations that Pfizer “made and /or disseminated unsubstantiated and/or false representations or statements about the safety and efficacy of” of the drugs Geodon, Zyvox, and Lyrica, and that Pfizer “offered and paid illegal remuneration to health care professionals to induce them to promote and prescribe” these drugs for various time periods between 2001 and 2008. Further, the agreement notes that the DOJ claims that such promotions were for ‘off-label’ uses, i.e. for uses not approved by FDA.

The settlement also resolves the federal government’s claims regarding “kickback” or other “illegal remuneration” paid by Pfizer “to health care professionals to induce them to promote and prescribe the drugs Aricept, Celebrex, Lipitor, Norvasc, Relpax, Viagra, Zithromax ,Zoloft, and Zyrtec,” from  “January 2001, through December 2004….” This “illegal remuneration” took the form of “speaker programs, mentorships, preceptorships,journal clubs, and gifts (including entertainment, cash, travel and meals)….”

What’s next:  increased government oversight of Pfizer

In addition, as part of the settlement, Pfizer has entered into a comprehensive five-year Corporate Integrity Agreement with the Office of Inspector General in the Department of Health and Human Services.  This allows monitoring for the next five years. Pfizer will also:

• Publicly disclose on its website information about payments to doctors, honoraria, travel or lodging;
• Notify doctors about this settlement and establish a mechanism by which doctors can report questionable conduct by any Pfizer representative;
• Undergo an annual audit of their Board of Directors;
• Have their senior executives certify annually that Pfizer is in compliance with the Corporate Integrity Agreement, and
• Proactively identify potential risks associated with promoting individual products and then it implement a plan to mitigate the identified risks.

If Pfizer fails to meet the requirements in its Corporate Integrity Agreement, it could face higher penalties AND be barred from inclusion in Federal health programs, like Medicare and Medicaid.

Pfizer: don’t settle for second:

Interestingly, Pfizer had paid $430 million to settle a criminal and civil case brought by federal and state prosecutors regarding the off-label promotion of the anti-epilepsy drug Neurontin. Entered into in just 2004, this agreement included what the DOJ described as a “$240 million criminal fine, the second largest criminal fine ever imposed in a health care fraud prosecution” at the time. However this new $2.3 Billion dollar settlement puts Pfizer in the lead, and easily outpaces the last government settlement for $1.42 Billion with Eli Lilly over the marketing of Zyprexa.  

The size of the new $1.2 billion criminal fine may be in response to that fact that Pfizer’s 2004 settlement also included a ‘compliance program.’  We hope this record fine, and the continued watchful eye of HHS will help to keep Pfizer in line. But with billions of dollars in profits from off-label promotion of their many drugs, only time will tell.

Benefits for consumers: not yet, but stay tuned

We here at PAL are glad to see this settlement, and to see signs that the DOJ is actively investigating abuses by the pharmaceutical industry.    Mr. Tony West, Assistant Attorney General for the Civil Division of the Department of Justice, describes what’s at stake:

“Illegal conduct and fraud by pharmaceutical companies puts the public health at risk, corrupts medical decisions by health care providers and costs the government billions of dollars. This civil settlement and plea agreement by Pfizer represent yet another example of what penalties will be faced when a pharmaceutical company puts profits ahead of patient welfare”

But this settlement does not include any compensation for consumers, union benefit funds, or insurers who paid for Bextra. A seperate agreement has been reached with Pfizer concerning their promotion of Bextra and Celebrex, with consumers and private, non-governmental insurers to share $89 million to settle suits brought by consumers and “third party payors” who alleged that they defrauded by Pfizer’s marketing and failure to disclose the risks of the drugs.  Please keep your eye on our blog, or check our website for updates on consumer settlements.