Biggest Off-Label Drug Marketing Scheme in US History - Part I - November 30, 2006

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Biggest Off-Label Drug Marketing Scheme in US History - Part I

First published November 30, 2006

The promotion and sale of two classes of psychiatric drugs, the atypical antipsychotics and selective serotonin reuptake inhibitors antidepressants (SSRIs), will go down in history as the most successful off-label marketing scheme of all time.

But unfortunately, before the illegal scheme takes its rightful place in the law books, a lot more deaths and injuries will be left in its wake.

In 2004, SSRIs and antipsychotics became the third and fourth best selling classes of drugs in the country, with sales of $20.7 billion, according to the July 27, 2005 Wall Street Journal.

The atypicals antipsychotics include Eli Lilly's Zyprexa; AstraZeneca's Seroquel; Bristol-Myers Squibb's Abilify; Johnson & Johnson's Risperdal; and Pfizer's Geodon.

According drug company SEC filings for the third quarter of 2005, the atypicals are still top money makers. For the 3 month period, sales of Risperdal reached $916 million, up 23%; Seroquel sales were $706 million, up 32%; Abilify reached $206 million, up 58%; Geodon had sales of $148 million, up 18%; and Zyprexa had sales of more than $1 billion.

Tax payers are the largest contributors to the off-label profits made from the atypicals. On October 23, 2005, the San Francisco Chronicle reported that "Nationwide, Medicaid programs purchase an estimated 60 to 75 percent of antipsychotic drugs."

In California, for instance, the highest Medicaid expense was for Zyprexa, at close to $250 million in the year ending June 2005. The atypicals accounted for four of the top 10 most expensive drugs in the 12 months prior to June 30, 2005, with California spending a combined total of over $620 million on the drugs.

The off-label marketing of these medications includes prescribing a drug for a different illness, or at a different dose, or with a different combination of other drugs, or for a different patient population than those approved by the FDA.

Its illegal for drug companies to promote drugs for uses that have not been approved but its common knowledge that they do it, and get away with it, continuously. But nowhere in the history of the FDA's regulation of the pharmaceutical industry has the off-label sale of specific medications been more blatant than with these two classes of psychiatric drugs.

An analysis of Florida Medicaid data from September 2002 to September 2003, by the Florida Department of Children & Family Services, found that 41,993 children, 12 and under, were given 190,210 off-label prescriptions for psychiatric drugs by doctors in fields that included anesthesiology, dermatology, geriatrics, allergy, nutrition, ophthalmology, obstetrics, pathology, otolaryngology, hematology, diabetes, plastic surgery, radiology, rheumatology and hand surgery.

People often ask how it is that doctors who specialize in these various fields of medicine would even think to prescribe psychiatric drugs off-label to begin with and critics are quick to point out that all roads of encouragement lead straight back to Big Pharma and the prescribing often begins because free samples of a drug are handy.

Critics say prescribing doctors are greatly influenced by drug sales representatives who provide them with free meals and other perks, along with the free drug samples and the skewed information from industry funded research.

Big Pharma also pays researchers to conduct studies on the drugs to come up with new uses to widen the customer net, and critics say the drug makers have this method of promoting off-label use down to a science.

First, the results of an industry funded study are published in a reputable medical journal, most often ghost-written by the drug maker or a PR firm, and then doctors who read the journal begin prescribing the drug for the new off-label use described.

And to cover all bases, the drug company feeds the journals money by purchasing thousands of copies of the study for sales representatives to distribute to all prescribing doctors to catch those who might not read the journals.

As part of this particular scheme to market the new psychiatric drugs, Big Pharma also funneled money to key state officials to make sure their new drugs would be included on the state formulary lists so they would be paid for by public health care programs.

For example, Allan Jones, a former fraud investigator in Pennsylvania, discovered a hidden slush fund account in Pennsylvania where drug companies were depositing money that was being accessed by state employees.

"They were given unrestricted educational grants," he explains, "that were deposited into an off-the-books account, unregistered, unmonitored, literally operated out of a drawer."

Mr Jones also discovered that drug makers were paying state employees directly and giving them perks such as lavish meals, trips and honorariums of up to $2,000 to speak in their official capacity at drug company events.

"It is illegal for a public employee to accept honorariums and to consult with industry without permission," he said, "yet it was happening openly."

After the new drugs were added to the state formulary list, according to Mr Jones, in 2003, Pennsylvania spent a combined total of $139 million for SSRIs and atypicals alone.

The off-label prescribing of atypicals is every bit as rampant as with SSRIs. On March 16, 2006, the Associated Press reported that soaring "numbers of American children are being prescribed anti-psychotic drugs -- in many cases, for attention deficit disorder or other behavioral problems for which these medications have not been proven to work," citing a study led by Dr William Cooper, a pediatrician at Vanderbilt Children's Hospital.

Between 1995 and 2002, the number of children covered by Medicaid and prescribed antipsychotics jumped 5-fold, to an estimated 2.5 million, the study said, or an increase from 8.6 children for every 1,000, to nearly 40 out of every 1,000 in 2002. "The increasing use of anti-psychotics," the Associated Press wrote, "corresponds with the introduction of costly and heavily marketed medications such as Zyprexa and Risperdal."

But the over-prescribing is not limited to kids on Medicaid. On May 11, 2006, the Associated Press reported that the use of atypicals by privately insured persons 19 and under had skyrocketed 80% in the four years ending in 2005, citing a report by Medco Health Solutions based on an analysis of over 2 million insured Americans.

The package inserts for these drugs come with no dosage recommendations for children even though experts say dosage issues have a higher importance when prescribing drugs to children because of their differing weights and developing bodies.

Doctors all over the country are prescribing these drugs in combination with one another for uses that have never been tested in any patient population. Medical professionals say its not uncommon to see patients, including very young children, on an SSRI, an atypical, an ADHD stimulant drug, and a sleeping medication all at the same time.

In fact, according to a study conducted by Medco Health Solutions, a managed-care firm, there has even been an 85% increase in the use of sleeping pills by children and young adults between 2002 and 2004.

New York Times reporter, Gardiner Harris, published an article on November 23, 2006, discussing the prescribing of off-label combinations of psychiatric drugs to children. For the article, he interviewed Andrew and Leslie Darr of Caldwell, Idaho, whose 2 sons were prescribed several psychiatric medications at the same time.

Mr Darr said that he was opposed to the drugging from the start. “When you come home from work and instead of getting them clawing at your feet and yelling, ‘Daddy, Daddy,’ you get a lethargic grunt, it just kills you,” he told Mr Harris.

Mrs Darr said that she was pressured by school officials to give her son Nicholas a stimulant drug when he was 6, and that his brother Nathan, a year younger, soon followed.

Three years later, the boys had a traumatic experience, and a month after that, both boys were hospitalized and given a diagnosis of bipolar disorder, with prescriptions for an antipsychotic, an antidepressant and a sleeping medication.

Atypical drugs are known for causing drastic weight gain. In three years, Mr Harris reports, Nicholas’s weight ballooned from 52 pounds to 140, and Nathan went from 48 pounds to 115. Neither boy got much taller, Mrs Darr told Mr Harris, and they both did poorly in school.

When another child in the family became ill, a nurse practitioner gave Mrs Darr free samples of an antipsychotic "to help her cope." After she began taking the drug, Mrs Darr said, she could not sleep or think straight and realized that she had been giving similar drugs to her sons for years and decided to wean them off the pills.

After the boys were off all medication for four months, their behavior normalized, the Darrs told Mr Harris, and they were transferred out of special ed into regular classrooms.

In an interview for the Times, Nicholas said the drugs "were not cool."

"You go to school and everybody thinks, 'Look at that retard,'" he told Mr Harris.

On October 8, 2006, California child and adolescent psychiatrist, Dr Elizabeth Roberts, author of, "Should You Medicate Your Child's Mind?" who has worked with children for more than 30 years, published an opinion piece in the Washington Post, and said, "the changes I have seen in the practice of child psychiatry are shocking."

"There was a time," Dr Robert writes, "when doctors insisted on hours of evaluation of a child before making a diagnosis or prescribing a medication."

Today, she says, some of her colleagues brag that they can make an assessment and write a prescription in less than 20 minutes and some parents have told her that it took their pediatrician only 5 minutes.

Dr Roberts says the loser in this race is the child "who must endure the side effects of these powerful drugs and be burdened unnecessarily with the label of a mental illness."

"Parents and teachers today," she says, "seem to believe that any boy who wriggles in his seat and willfully defies his teacher's rules has ADHD."

"Likewise," she notes, "any child who has a temper tantrum is diagnosed with bipolar disorder."

"Psychiatrists are now misdiagnosing and overmedicating children for ordinary defiance and misbehavior," she writes in her editorial.

"The temper tantrums of belligerent children," she says, "are increasingly being characterized as psychiatric illnesses."

But the off-label over-prescribing of atypicals is happening with all age groups. A June 2005, study in the Archives of Internal Medicine reviewed nearly 2.5 million Medicaid beneficiaries in nursing homes and found that more than 200,000 residents received antipsychotics that had "no appropriate indications for use."

A study conducted at the University of Georgia in the June 2006, Journal of Clinical Psychiatry, reviewed prescribing records for 107,000 Medicaid recipients on drugs that act on the central nervous system and found that 75% of SSRI patients and 64% of atypical patients received at least one of these drugs for an off-label use, and most of the time without the patient's knowledge.

However, doctors whose off-label prescribing habits have increased due to the influence of Big Pharma without the knowledge of their patients may soon find themselves sitting along side of defendant drug companies in courtrooms, legal analysts say.

Although no law in any state specifically requires doctors to tell their patients when a drug is prescribed off-label, in some states like California, judges may now allow injured patients to use a doctor's lack of disclosure to bolster a malpractice suit, according to the May 5, 2006 San Francisco Chronicle.

California law does not explicitly require doctors to reveal that they are prescribing a drug off-label, the Chronicle says, but a jury might conclude on its own that the patient needed that information to make an informed choice. "If a jury reached that conclusion," it states, "the liability could be increased for a physician who didn't disclose the drug's off-label status."

Attorney, Barry Turner, Lecturer in Law at Leeds Law School in the UK is an academic lawyer who has been involved in litigation related to the off-label marketing and promotion activities involving Big Pharma for several years.

He says combing drugs, or polypharmacy, can be a dangerous practice for doctors even in general medicine. But at least in cases like diabetes or heart disease, he says, cause and etiolgy are often known and understood, making decisions about the risks and benefits of multiple medications possible.

"That knowledge is totally absent in psychiatry," Mr Turner reports. "While the data on efficacy of multiple medications is 'zero - zip'," he says, "the data on side effects and adverse drug reactions is not."

"Polypharmacy, based on hit and miss 'diagnosis', guesswork and belief systems rather than science," he warns, "is dangerous hokum and a ripe territory for negligence actions."

In her book, "The Truth about Drug Companies: How They Deceive Us and What to Do About It," Dr Marcia Angell, former editor of the New England Journal of Medicine, tells patients to ask the following questions before accepting a prescription for a new brand-name drug:

(1) What is the evidence that this drug is better than an alternative drug or treatment approach?

(2) Has it been published in a peer-reviewed medical journal, or are you relying on information from drug company representatives?

(3) Is this drug better only because it's given at a higher dose?

(4) Would a cheaper drug be as effective if it were given at an equivalent dose?

(5) Are the benefits worth the side effects, the expense and the risk of interactions with other drugs I take?

If its a free sample, Dr Angell says to ask the doctor whether there is a generic drug or other less-expensive equivalent to take when the free sample runs out.