Part 1 of 3 parts; Off-label prescribing of prescription drugs: Profits for big pharma and risk to patients
By Evelyn Pringle
Online Journal Contributing Writer
May 30, 2006, 00:54
prescribing of drugs has become a serious problem over the past decade. Doctors
are adjusting dosage levels and prescribing drugs for medical indications and
treatment durations for which the drugs were never approved or intended.
When the FDA
approves a drug, it also approves the labeling for the drug, which explains the
manner in which the medication is to be used. While physicians may prescribe
approved drugs as they see fit, its against the law for drug companies to
promote drugs for uses outside of the approved labeling but they do it all the
the most notorious example of an illegal, but highly successful, off-label
marketing campaign. The drug was approved for the limited use of treating
epileptic seizures but nonetheless, became an overnight blockbuster with sales
that soared from $97.5 million in 1995, to more than $2.5 billion in 2003.
might be the most notorious, it is certainly not the only problem. A study
published in the May 8, 2006, Archives of Internal Medicine, determined that
more than one out of every seven prescriptions written for 160 commonly used
drugs were for off-label uses that lacked scientific support.
The study was based
on information from the IMS Health National Disease and Therapeutic Index that
defines drug prescribing patterns and provides market data on drug companies.
In 2001, an
estimated 150 million prescriptions, or 21 percent of prescriptions written,
were for off-label use, according to the Archives study.
To reach its
results, the study first determined whether a prescription was off-label and
then assessed the level of available scientific evidence supporting the use,
through the Drugdex system, a comprehensive summary of evidence supporting
off-label uses of prescription drugs.
The study found that
73 percent, or 109 million off-label prescriptions, had little or no supporting
evidence. The study does not explain why doctors prescribe so many drugs
off-label but one explanation may be that "both physicians and patients
have misunderstood the role of the FDA," the study's lead author Randall
"I think there's
sort of a presumption that if a drug has made it onto the market," he
notes, "the FDA has vouched for its safety and efficacy for all of its
One way drug
companies have been able to increase the off-label sale of drugs is by influencing
doctors in public institutions, and state policy makers, who are involved in
the development of drug formularies that list which drugs will be used in state
institutions and by persons covered by government health care programs like
Medicaid and Medicare.
Allen Jones, a
former Pennsylvania fraud investigator, explains that each state has a menu of
approved drugs that doctors must prescribe to persons in state institutions.
"Before a drug can be prescribed by a state physician for somebody in the
state system," he says, "it has to be on the list."
According to Mr
Jones, the drug companies "have bought the decision-making process from
our government officials all the way down to the guy who decides what drugs get
on the formulary."
Doctors who sit on
the expert panels and decide which drugs will be on the lists, he says, are
paid by drug companies to give positive opinions in order to circumvent the FDA
"The FDA has no
control over what an individual doctor does or says," Mr Jones explains,
"the pharmaceutical industry has funded a mechanism whereby they can
gather favorable opinions."
amplify and magnify those opinions," he says, "and put them in the
form of a treatment protocol that can be implemented in any state with the
approval of a few key decision-makers."
Stacking the deck
with industry friendly "experts" is apparently common. An
investigation by the scientific journal Nature found "extensive"
financial connections between drug companies and the advisory panels, with as
many as 70 percent of the panels affected. In one instance, Nature found every
member of a panel had received payments from the company making the drug that
In the summer of
2002, Mr Jones discovered an off-the-books account where drug companies were
depositing "educational grants" from which state officials and policy
makers involved in developing Pennsylvania's drug list were receiving payments.
"We had state
officials accepting $2,000 honorariums," he noted, "and physicians who
were taking trips, perks and gratuities."
One of the officials
Mr Jones named in his investigation was the state pharmacist, Steven Fiorello.
In April 2005, the State Ethics Commission fined Fiorello over $27,000 after
finding that he repeatedly took money from drug makers, Pfizer and Janssen,
while serving on the panel that decided which drugs could be given at 9 state
mental hospitals. The commission's report cited repeated failures to disclose
his income from the drug companies.
On June 10, 2005, Senators
Chuck Grassley and Max Baucus announced the beginning of an investigation by
the Senate Finance Committee, which has oversight responsibility for government
health care programs, into the practice where drug companies give money to
companies call the awards educational grants," their press release said,
"but the senators are concerned that the dollars are more focused on
product promotion than education."
The senators said
their inquiry was based on reports that companies have awarded grants as
inducements to prescribe medications the companies produce.
In some cases, they
said, "such grants to state agencies may have prompted those agencies to
develop programs leading to over-medication of patients at the expense of
patient health or to unnecessary expense for taxpayers."
"We need to
know how this behind-the-scenes funneling of money is influencing decision
makers," Senator Grassley said. "The decisions result in the
government spending billions of dollars on drugs."
In recent years,
investigations into the prescribing patterns for people on Medicaid and
Medicare have led to the discovery of a drastic increase in off-label
prescribing to children and the elderly of drugs never approved for use in
children and the elderly.
One class of drugs
found to be prescribed off-label most often without scientific support are
psychiatric medications. In 96 percent of the psychiatric drugs prescribed
off-label, the Archive study found support was lacking.
According to the report,
Death by Medicine (2003), by Gary Null, PhD; Carolyn Dean MD, ND; Martin
Feldman, MD; Debora Rasio, MD; and Dorothy Smith, PhD, a study on prescription
drug use by the elderly conducted by Medco Health Solutions found that 6.3
million senior citizens received more than 160 million prescriptions and a
total of 7.9 million medical alerts were triggered by off-label prescribing,
with 2.2 million alerts indicating excessive dosages unsuitable for seniors,
and about 2.4 million indicating clinically inappropriate drugs for the
Drug companies have
promoted the off-label use of psychiatric drugs with children even after their
own studies have shown the drugs to be dangerous. In 2004, New York Attorney
General Eliot Spitzer filed a lawsuit against GlaxoSmithKline for withholding
studies that raised doubts about the effectiveness and safety of Paxil in
treating children and revealed that more than 2 million prescriptions for Paxil
were written off-label to treat children in 2002.
In late 2004, the FDA
ordered black box warnings on all SSRI antidepressants after it was discovered
that drug makers had suppressed studies that showed the drugs were linked to an
increased risk of suicide in children.
Documents that have
surfaced during litigation reveal that drug makers knew about this risk before
the SSRI antidepressants arrived on the market, but continued to find ways to
get doctors to prescribe the drugs to kids. A report by Express Scripts, Inc, a
pharmacy benefit manager, titled "Trends in the Use of Antidepressants in
a National Sample of Commercially Insured Pediatric Patients," shows that
between1998 and 2002, the overall use of antidepressants among children
increased from 160 children per 10,000 in 1998, to 240 per 10,000 in 2003.
daughter Julie hanged herself after being prescribed the antidepressant Zoloft
off-label. He is angry at the Bush administration and the FDA for failing to
protect the public against drug companies who hide studies that show drugs are
dangerous when given to children.
"It is clear
that the FDA is a political entity and its leadership has protected the
economic interests of the drug industry," he says.
According to Mr
Woodward, officials in leadership positions have strong ties to the industry.
"FDA's chief counsel Daniel Troy has spent his career defending the drug
industry," he noted, "if a study does not favor a drug, the public
never hears about it."
"Under the Bush
administration," Mr Woodward said, "the FDA has placed the interests
of the drug industry over protecting the American public."
He points out that
86 percent of the millions of dollars in campaign contributions by drug
companies went to Bush and Republican candidates and wants to know, "What
did Pfizer, Eli Lilly, and GlaxoSmithKline Beecham buy?"
A recent study
reveals that even when the FDA does add a black box warning to a label, the
highest form of drug safety alert available, doctors will continue to prescribe
The February 14,
2006, Archives of Internal Medicine featured a report on a study where
researchers reviewed the records of 324,548 patients seen at several Boston
area medical facilities between January 1, 2002, and December 31, 2002, and
found that 33,778 patients were prescribed a drug that had a black box label,
and 2,354 of those prescriptions were written contrary to the guidance set
forth in black box warning.
The study found that
in about 1,000 cases, patients were taking one drug at the same time as another
drug when the warning said that taking the two drugs together should be
avoided, and in about 90 percent of the cases, a drug was prescribed to treat a
condition for which the drug was not approved.
According to Death
by Medicine, each year approximately 2.2 million US hospital patients
experience adverse drug reactions to prescribed medications and experts say
many are caused by prescribing drugs for uses not approved.
off-label prescribing practices have come under scrutiny in recent years
because so many of the drugs are covered by government health care programs,
and lawmakers charged with oversight of programs like Medicaid and Medicare
became suspicious about the skyrocketing prescription drug costs.
In some of the
largest cases involving Medicaid and Medicare fraud, former industry employees
came forward with information about marketing schemes and filed lawsuits under
the False Claims Act.
DC-based Taxpayors Against Fraud, is a non-profit organization dedicated to
combating fraud against the federal government through the promotion and use of
the qui tam provisions of the False Claims Act.
Qui tam is a
mechanism that allows persons with evidence of fraud to bring suit on behalf of
the government. TAF educates the public about the FCA and its qui tam
provisions and provides assistance to whistleblowers and their attorneys and
sometimes files amicus curiae briefs on important issues.
TAF also has a staff
of lawyers and other professionals who are available to assist anyone
interested in the FCA and publishes the False Claims Act and Qui Tam Quarterly
lawsuits are proving to be highly effective in exposing fraud. Of the10 top FCA
Medicaid fraud recoveries to date, the top five are whistleblower cases against
According to TAF, during
FY 2004, between October 1, 2003 and September 30, 2004, the US Department of
Justice settled 3 whistleblower cases against drug companies for a total of
over $800 million, raising the total recoveries in such cases by nearly 50
percent to $2.46 billion.
Two of the
settlements involved both criminal fines and civil penalties. The recoveries
included $290 million in criminal fines, $275 million in civil penalties and
damages to the federal government, and nearly $235 million to state
governments. All three settlements involved allegations of fraud against
Two of the cases
began as lawsuits filed under the FCA by whistleblowers and the third began as
a case under the Texas Medicaid Fraud Prevention Act.
The defendant in one
case was the nation�s largest drug maker, Pfizer, with annual sales of $30
billion. The conduct at issue concerned a Pfizer subsidiary, the Parke-Davis
Division of Warner-Lambert, acquired by Pfizer in 2000.
Schering-Plough was the defendant in the other two cases.
recoveries from Pfizer totaled $430 million, and the two Schering settlements
were $345 million and $27 million.
This is the second FCA
whistleblower settlement entered into by Pfizer, and the second largest drug
maker settlement ever when measured by the combined civil recovery of $430
million and the criminal fine of $240 million.
Part 2: Tactics Pfizer
used in promoting off-label use of Neurontin
Evelyn Pringle is a
columnist for OpEd News and an investigative journalist focusing on exposing corruption in government.
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