[Also posted on Postscript]

The guilty plea and $1.5 billion settlement by Abbott to resolve their illegal off-label promotion of Depakote revealed a saga of extensive industry abuses and influence peddling that put millions of vulnerable seniors at risk. Abbott’s extensive promotion of the unapproved uses of the anti-convulsant drug Depakote to treat both seniors with dementia and to treat children is shocking. But it is even more alarming that this not the first major drugmaker to plead guilty to illegal marketing tactics that have targeted this exceptionally vulnerable population of seniors.

Many may recall that Eli Lilly was caught illegally promoting the unapproved, or “off-label” use of the antipsychotic drug Zyprexa to treat seniors with dementia, despite their internal studies showing that the risk of death from this drug increased in elderly patients.

Marketing these drugs to nursing homes for use on patients who ‘act up’ or are unruly has been a lucrative strategy for drugmakers. In response, we applaud the Department of Justice and the State Attorneys-General for their increasingly aggressive litigation to penalize these dangerous and unconscionable marketing practices.

But unfortunately for the millions of seniors who may be given Depakote or Zyprexa today or in the near future, the record-breaking $1.4 and $1.5 billion settlements respectively may not translate into improved care, unless further action is taken.

We urge Medicare and Medicaid officials at the federal and state level to move quickly to develop and implement safeguards, such as prior approvals or mandatory second opinions, that could be put in place to protect these vulnerable seniors from any unwarranted or inappropriate use of the drug Depakote to treat their dementia.

Looking forward, it’s time that all off-label settlements by the DOJ or the states include a requirement that the drugmaker pay to correct the misinformation that off-label marketing creates – i.e. that a drug is safer or more effective than it really is. Using lawsuits to fund corrective educational campaigns has a long history, both in public and private sector litigation. (See description here.)

To help stop the inappropriate and potentially harmful overuse of Depakote, Zyprexa, or Risperdal from continuing, doctors should be retrained to undo the misinformation campaigns by Abbott, Eli Lilly, and Johnson and Johnson. Several states, including Pennsylvania and New York have implemented “academic detailing” programs that send independent medical experts, usually nurse practitioners and pharmacists, to provide doctors with the truth about how effective drugs are from an objective, evidence-based perspective. Many state programs specifically address mental health drugs such as Zyprexa and Depakote. Indeed, one of the first of these education programs designed by Dr. Jerry Avorn, who spearheaded the concept in the 1990’s, recommended that a little tender loving care by nursing home staff could reduce the inappropriate use of sedatives, common at that time. A similar conclusion was reached by some nursing homes profiled in an  inspiring Boston Globe article addressing the overuse of Depakote.

– Wells Wilkinson,
Director, Prescription Access Litigation
Staff Attorney, Community Catalyst

Posted May 29th, 2012

The Affordable Care Act created some desperately needed means to start controlling ever-rising health care costs. Many — like preventive care or delivery reforms — will take some time to realize savings. In contrast, new anti-fraud efforts look to be paying off right away, in amounts much bigger than expected.

The health reform law provided $350 million over ten years to increase anti-fraud investigation and enforcement resources for the Department of Justice (DOJ) and State Attorneys-General. The goal? Saving $6.4 billion over the next decade. Given that some estimate that fraud and waste cost as much as $60 billion a year, or $600 billion over a decade, saving one percent of that amount seems a pretty modest impact.

But wait! New estimates project that current or pending settlements of drug fraud litigation by the DOJ and the Attorneys-General will top $8 billion in FY2012 alone, according to the group Taxpayers Against Fraud. (See list below.) This is not the culmination of hundreds of lawsuits; it’s just the eight biggest. So it looks like this anti-fraud effort under the ACA will meet and then surpass its ten-year goal in less than two years!

To be fair, most of these eight drug fraud investigations were undoubtedly underway before the increased funding for anti-fraud efforts reached the DOJ and State Attorneys-General offices. But there is little doubt that providing these over-worked regulators with increased resources was a big help in increasing enforcement. DOJ probably has fewer lawyers working on all their pending drug fraud cases than some of the biggest drugmakers hire to defend a single lawsuit. But despite these disparities, these results show that very modest government investment in fighting fraud, coupled with hard work by government lawyers and whistleblowers, can pay off big.

For example, earlier this week drugmaker Abbott Labs in Chicago settled a civil and criminal investigation of their illegal promotion of the anti-convulsant drug Depakote as an unapproved treatment of dementia in seniors, and of various conditions in children. Abbott pleaded guilty to promoting these unapproved, or ‘off-label’ uses of Depakote, and agreed to pay $1.6 billion – one of the biggest settlements for the illegal promotion of a single drug.

There could be as many as a couple hundred pending whistle-blower lawsuits that are filed under seal and being investigated now by the federal or state regulators. These pending lawsuits may add up to billions of dollars of additional fines and settlements.

Some critics have warned that even billion-dollar fines are an inadequate deterrent when a drug company can make far in profits on illegally promoted sales of a drug.

For instance, the $1.4 billion record-breaking settlement with Eli Lilly in 2009 for illegal promotion of their antipsychotic drug Zeprexa was less than 5 percent of Lilly’s gross sales. Eight months later, DOJ shattered this record with an even bigger $2.3 billion settlement, which amounted to 14 percent of Pfizer’s gross sales of eight illegally marketed drugs (see here).

Similarly, this month’s $1.6 billion Depakote settlement is nearly 12 percent of the drug’s $13.8 billion in gross sales revenue from 1998 to 2008. Furthermore, DOJ is pioneering two mechanisms to deter future illegal conduct by Abbott, along with this hefty fine.

First, the Depakote settlement places Abbott on probation and imposes a corporate compliance and monitoring program, for five years. If Abbott violates the compliance agreement or significantly violates the law, the government can exclude Abbott, and all their drug products, from federal health care programs. That would cost Abbott billions in lost sales on numerous drugs.

The settlement also aims to hold Abbott’s corporate leadership personally accountable. Abbott’s CEO must personally certify compliance and the board of directors must review and report on compliance each year. If the CEO or the board is lax in these duties, they could be excluded from their positions at Abbott. And if CEO or board intentionally lie to the government to cover up any misconduct, they could face personal criminal liability under the federal False Statements Statute. (Find the plea agreement and related documents here.)

Sadly, Abbott’s illegal promotion of ineffective and dangerous uses of Depakote has both harmed and put at risk what is arguably the most vulnerable patient population – seniors suffering from dementia, who live away from their families in nursing homes. Undoubtedly millions of seniors were, and likely continue to be given Depakote inappropriately as a result of Abbott’s illegal promotional campaign.

Check back soon for more on (1) actions that Medicare and Medicaid can take to address the continuing effects on patients of illegal promotions of off-label use of drugs and (2) how the Arkansas AG fought prescription drug fraud, winning huge fines to plug the state’s Medicaid budget deficit.

Wells Wilkinson

Director, Prescription Access Litigation

Staff Attorney, Community Catalyst

Projected Drug Fraud Settlements in FY 2012, excerpted from the Taxpayers Against Fraud website.

A version of this blog was posted earlier on Health Policy Hub and Postscript. 

We write frequently on this blog about “off label” marketing — that’s the practice of prescription drug & medical device companies illegally promoting their products for uses or conditions that are not approved by the FDA.

Here’s the “elevator” version of what off-label marketing is and why it’s illegal:

Before any prescription drug can be sold in the U.S., the Food and Drug Administration must find that the drug is “safe and effective” for the conditions that the company wants to sell it for and at the dosages that it seeks to sell. However, once it’s on the market, a doctor can prescribe it for any condition or purpose or type of patient, regardless of whether the FDA approved it for that or not.

In some specialties (particularly oncology), off-label is very common and is the so-called “standard of care.” Important new uses for drugs have at times been found through off-label prescribing. Since many drugs are not tested on children as part of FDA approval, much (possibly most?) pediatric prescribing is off-label.

So off-label prescribing is perfectly legal (as long as it doesn’t go so far afield that it constitutes malpractice) and is not regulated by the FDA. However, off-label marketing is very much illegal – it’s considered “misbranding” under section 502(a) of the Food Drug and Cosmetics Act (FDCA). In other words, a drug company cannot promote a drug for off-label purposes — because the off-label use has not been shown to be safe and effective, is an end-run around the FDA’s approval process, and eliminates the drug company’s incentive to submit an application to have the off-label use approved.

Back in February, the FDA published its Draft Guidance for Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices and requested public comment on its proposed rules.

Today, we at Prescription Access Litigation, along with our colleagues at The Prescription Project, National Physicians Alliance, and US PIRG submitted our comments, calling on the FDA not to issue the Draft Guidance as a final Guidance. The FDA’s Draft Guidance would make it much easier for pharmaceutical companies and their salespeople to distribute reprints of medical journal articles discussing off-label uses to physicians.

It is ironic that the FDA is working to make it easier for drug companies to market drugs for off-label purposes when there have been so many revelations and allegations of egregious illegal off-label marketing in the past few years, including off-label marketing of Pfizer’s Neurontin (which resulted in a $430 Million settlement with the U.S. Attorney and state Attorneys General), and of Eli Lilly’s Zyprexa.

Among the reasons we cite for why the FDA’s draft guidance is a bad idea:

“Distribution of single studies by pharmaceutical representatives is not an effective way to facilitate evidence based decision making and thus does not prioritize patient safety or public health. Specifically:

• Early evidence is often contradicted.
• Single trials can be misleading and may not adequately assess drug effectiveness or
  safety.
• Statistically, any individual study has a good chance of coming to the wrong
  conclusion.
• Trials stopped early for benefit are found to be less striking on further review.

The Draft Guidance would allow drug companies to distribute journal articles from any peer-reviewed medical journal. However, as we point out in our comments:

“The FDA drug approval process requires review of all data regarding a drug, both published and unpublished. In contrast, the editorial review processes employed by peer reviewed journals do not. Journal review processes vary widely and publication in a peer reviewed journal is not in and of itself a guarantee of quality.

• FDA approval requires access to full data.
• Journal reviewers only have access to what has previously been published.
• Published studies may lack appropriate controls, design or statistical analysis.
• Industry has the potential to fund and publish individual studies with substantial bias.
• Industry-funded trials and reviews are more likely than independent evaluations to be
  favorable toward the sponsor’s drug.
• Publication bias means negative studies are less likely to be known by reviewers.
• Industry, motivated to sell more product, could selectively choose to distribute studies
  that show its products in a favorable light.
• Industry has frequently been shown to play an invisible role in funding and even
  “ghost writing” published studies that are published under the names of academic
  physicians.
• FDA lacks resources to review all distributed studies and ensure they meet a high
  standard.

To see our comments in their entirety, go here.

To see the other comments that have been submitted and the full text of the draft guidance, go here.

The New England Journal of Medicine ran a terrific “Sounding Board” piece just last week on this topic by Drs. Jerry Avorn & Aaron Kesselheim of Brigham & Women’s Hospital: Pharmaceutical Promotion to Physicians and First Amendment Rights (subscription required)