OFF-LABEL MARKETING OF PHARMACEUTICALS PRODUCTS - This is my first credit seminar presentation over off label promotion of pharmaceutical products.Please ignore the minor formatting errors.
4. off-label marketing PRESENTED BY : VIRENDRA KUMAR SEMESTER-
I ROLL-NO : 32 MBA(PHARM)
5.
Off-label use
Off-label marketing
Off-label prescription
Off-label promotion
Case studies
Drugs commonly used off label
FDAMA-1997
Concluding remarks
off-label marketing
6.
The FDA regulates the manufacture, labeling, and promotion of
drugs
In the NDA, the applicant has to prove that the drug is safe
and effective for various uses
These uses become the labeled usesthe uses for which the tests
have been conducted.
Once a drug is approved by the FDA, various medical researchers
and practictioners may discover that such drugs have other valid
(off-label) uses.
off-label marketing
7.
The FDA does not regulate the practice of medicine
It is completely legal for physicians to prescribe
pharmaceutical drugs for off-label uses, so long as what they are
doing is not research
off-label use of pharmaceutical drugs could potentially subject
doctors to liability for malpractice.
off-label marketing
8.
Off-label prescription
FDA regulations pro hibit DTC promotion & restrict
physiciantargeted promotion
Unproven off-label use may be costly and threaten patient
safety
off-label marketing
9.
FDA
focuses on market entry
historically maintained a hands-off approach
Sometimes little market incentive to seek approval for
additional indications:
older & generically available drugs
population size too small
No alternatives exist: orphan drugs & pediatric
Desire to broaden therapeutic alternatives:
failure of standard therapy
innovation seeking behavior
off-label marketing
10.
Have a huge stake in off-label uses of their products
One source estimates that 40 percent of the prescriptions are
off-label
In general, drug manufacturers are not allowed by statute and
the FDA to promote off-label uses for the products
Not allowed to advertise off-label uses
Not allowed to induce physicians to prescribe off-label
uses
off-label marketing
11.
Clinically Reasonable
Well-known evidence based-therapy
Supported by treatment guidelines
Other drugs in class are indicated
Cost-effective generic substitution
Innovative approaches when standard therapies fail
Concerns
May not bear same degree of clinical or scientific scrutiny as
labeled indications
Inconclusive evidence:
contraindications
safe dose
ADRs
Over use of unproven off-label therapies may be costly
off-label marketing
12.
In general, doctors may prescribe a drug for unapproved
uses
In general, manufacturers may not promote unapproved uses.
Benefits: some off-label uses are scientifically valid and
provide tremendous benefits to patients, especially in areas of
life-saving drugs
Risks: no guarantee of scientific validity; unknown health
risks; waste of public resources; certain side effects not
justified
off-label marketing
13.
Profit motive:
-Clinical trials costly
-Off-label sales can be significant
-These factors can affect corporate judgment
Off-label promotion relies on covert marketing techniques
Before 1997, FDA allowed dissemination of information about
off-label uses only when such information was solicited by the
physician
off-label marketing
14. off-label marketing Figure 1. Proportion of Off-Label
Prescribing by Functional Class
15. off-label marketing
16.
In June 2004,Pfizer had paid $ 430 in fine and civil
judgments
Acc. To FDA ,the Parke Davis division of Warner Lambert (which
was acquired by Pfizer in 2000) was aggressively marketing
Neurontin for off-label uses.
off-label marketing
17.
Neurontin (gabapentin) is indicated as adjunctive therapy in
the treatment of partial seizures with and without secondary
generalization in adults with epilepsy, at doses ranging between
900 mg to 1800 mg per day
Payments to physicians (~$ 50 million to 3,000 physicians)
-Grants
-Speaker fees
-Honoraria
-Paid vacations
-Olympics tickets
Ghostwritten articles
Suppress negative information
off-label marketing
23.
US Patent 5,084,479: Neuro-degenerative diseases (1990)
US Patent 5,510,381: mania and bipolar disorder (1995)
US Patent 5,792,796: anxiety and panic (1995)
US Patent 6,242,488: pain (2000)
US Patent 6,426,368: alcoholism (2001)
off-label marketing
24.
Initial estimate for lifetime sales of Neurontin was $500
million
Off-label marketing was successful: in 2003 use of Neurontin
for unapproved uses accounted for nearly 90% of its sales
Sales of Neurontin now exceed $2 billion annually
off-label marketing
25. off-label marketing PAIN (NEURONTIN V. DILANTIN)
26.
Warner-Lambert pled guilty to two counts of violating the Food
Drug & Cosmetic Act
Warner-Lambert paid $430 million:
-$152 million to settle federal civil False Claims Act
liabilities
-$38 million to settle its state civil liabilities to the fifty
sates and fund remediation program
-$240 million federal criminal fine
off-label marketing
27.
Approximately 40% of all drug use is off-label
33% of all prescriptions in cancer treatment
81% of patients with AIDS receive at least one drug
off-label
56% of all prescriptions for antidepressants
Nearly all pediatric patients are prescribed drugs
off-label
Source: Tabarrok, 2000
off-label marketing
28.
Otsuka American Pharmaceutical, the US unit of the Japanese
drugmaker, agreed to pay more than $4 million to resolve
allegations that it marketed the Abilify antipsychotic for
off-label uses, according to the US Department of Justice .
From 2002 through 2005, Otsuka knowingly promoted the sale and
use of Abilify for pediatric use and to treat dementia-related
psychosis, although at the time, the FDA had not approved the drug
for use in geriatric patients, teenagers or children.
Pharma Blog - 2008 March 27 CASE-2 se 2
29.
Botox example
1989: FDA approved for facial neurological movement
disorders
2002: FDA approved to combat wrinkles and excessive underarm
sweating
Currently, FDA approved for both
cosmetic and therapeutic uses
Until 2002, it wasnt illegal from FDA to use Botox for wrinkles
but it was prohibited to advertise it for wrinkles
off-label marketing
30.
ASPIRIN (used off- label till 1998,to reduce the risk of heart
attack)
Viagra (off-label use for erectile dysfunction)
Minoxidil (used off-label for hair growth)
off-label marketing
31.
GABAPENTIN (anticonvulsant)
83%: 20% supp. / 80% no supp.
AMITRIPTYLINE (psychiatric:tri-cyclic antidepressant) 79%: 25%
supp. / 75% no supp.
ISOSORBIDE MONONITRATE (cardiac: nitrate)
75%: 64% supp. / 36% no supp.
DIGOXIN (cardiac: dysrythmia)
66%: 38% supp. / 62% no supp.
RISPERIDONE (psychiatric: anti-psychotic)
66%: 1% supp. / 99+% no supp.
off-label marketing
32.
ACTIQ By Cephalon, oral tarnsmucosal fentanyl citrate(OTFC) is
used off-label to treat moderate to severe chronic, non-malignant
pain even though it is FDA-approved solely for break-through pain
in cancer patients.
Bevacizumab (Avastin, Genentech/Roche) is a monoclonal antibody
against vascular endothelial growth factor (VEGF). has been used
against Age Related Macular Degeneration, but the evidence for its
use is anecdotal.
off-label marketing
33.
Carbamazepine , or Tegretol, has been used as a mood stabilizer
and is accepted treatment for bipolar disorder .
Methotrexate (MTX), approved for the treatment of
choriocarcinoma, is frequently used for the medical treatment of an
unruptured ectopic pregnancy. There is no FDA-approved drug for
this purpose and there is little incentive to sponsor an unpatented
drug such as MTX for FDA-approval.
off-label marketing
34.
In 1997, Congress passed FDAMA allowing manufacturers to
disseminate information about off-label uses to health care
providers under certain circumstances
FDAMA purports to liberalize the dissemination of information
regarding off-label use to health care professionals, but the
requirements for legally disseminating such information are
burdensome
off-label marketing
35.
Off-label marketing had benefited in past by unveil the unknown
uses of drugs ,but at the same time ,case like Neurontin etc..shows
that it has detrimental effect on people who were victims of
Off-label marketing.
Physicians need to understand their responsibility