[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. 

Consumer Reports recently published a list of drugs that have heightened risks for older adults, due to the fact that as kidneys age, they lose some ability to process drugs. Consumer Reports compiled a “list of medications that are best avoided by those 65 and older, as well as a list of alternative medications.” See below:

Medicines Older Adults May Want to Avoid

Adverse drug reactions that result in emergency room visits affect older Americans nearly twice as often as young people. One reason is that as the body ages, the kidneys’ ability to process medications declines. As a result, some drugs stick around longer in the body, and others can build up to unhealthy levels if multiple doses per day are required.

At the same time, millions of older Americans take five or more medications a day, which multiplies the risk of experiencing an adverse drug event.

Consumer Reports Health has published new information to help guide people in their drug selections. A list of medications that are best avoided by those 65 and older, as well as a list of alternative medications, is included.

For example, antihistamines Chlor-Trimeton (chlorpheniramine) and Benadryl (diphenhydramine) can cause confusion, sedation and the inability to fully empty the bladder (urine retention) in people over 65. Generic cetirizine (Zyrtec), fexofenadine (Allegra) and loratadine (Claritin) are generally safer bets.

Another example is pain relievers. Aleve and Naprosyn (naproxen), Daypro (oxaprozin) and Feldene (piroxicam) can cause gastrointestinal bleeding and kidney damage. Demerol (meperidine) can cause confusion and falls. Better and safer choices include Tylenol (acetaminophen), Advil (ibuprofen), Zostrix (capsaicin cream) and for severe pain, morphine.

Click here for a complete list of drugs to avoid for older individuals.

Find more information at Consumer Report’s Best Buy Drugs about comparative effectiveness
and comparative cost for many of these medicines.

The Government Accountability Office released a report today, finding that “in several key areas, FDA rules for drug approval fail to guarantee the safety and effectiveness of drugs for seniors.” Among the problems identified:

• Inclusion of seniors in clinical trials. GAO found that drug manufacturers “generally included elderly persons and reported safety and effectiveness data for elderly persons in clinical trials.” However, in a number of cases, selected drug trials excluded participants on the basis of age, restricting the participation of seniors.
• Inadequate FDA guidance. FDA has failed to clarify important requirements in the drug evaluation process for seniors, resulting in potential information gaps. For example, FDA does not require that medical officers determine whether a sufficient number of seniors participated in drug trials.
• Failure to document safety and effectiveness. According to GAO, one-third of new drug reviews failed to include documentation of FDA medical officers’ review of drug safety and effectiveness data for seniors.

Of these, excluding or failing to recruit adequate numbers of seniors for drug trials is the most troubling. Since the clinical trials are the only data that the FDA has to determine whether a drug is safe and effective for the population that will be using it after approval, it is vitally important that the clinical trial participants be a microcosm of the much larger patient population that is likely to use the drug once it’s approved.

We know that some side effects don’t show up in clinical trials, either because of the smaller number of people taking the drug or because some side effects only surface after patients have used the drug for longer periods. The FDA at times requires drug makers to conduct “post-marketing studies” after the drug has been approved — studies designed to ferret out the drug’s true risks and side effects once the “real world” data from millions of uses are available. Yet last year, the Office of the Inspector General issued a report documenting the incredibly shoddy job the FDA does at following up and making sure that drug companies actually do these studies.

The FDA’s failure to ensure that post-marketing studies are conducted makes it all the more important that clinical trials conducted to get the drug approved accurately reflect the patient population that is likely to take the drug once it’s approved. This is doubly important for seniors, who take more drugs, are likelier to suffer side effects, and far likelier to have other, complicating conditions.