Download LEGAL CONSIDERATIONS REGARDING FORMULARY DECISIONS

FDA REGULATION:
EFFECT ON PAIN
MANAGEMENT IN THE ED
RICHARD R. ABOOD, R.Ph., J.D.
Professor Pharmacy Practice
University of the Pacific
ROLE OF THE FDA
• The FDA must approve a drug as safe and
effective for the conditions indicated in
the labeling prior to marketing.
• All labeling content must be approved by
the FDA
LABELING REQUIREMENTS
Prescription drug labeling must be
directed to the health care
professional (not the patient) and
include warnings describing serious
adverse reactions and potential
safety hazards.
(21 CFR 201.56 & 201.57)
“BOXED WARNINGS”
“Special problems, particularly those that may
lead to death or serious injury, may be required
by the Food and Drug Administration to be
placed in a prominently displayed box.”
(§201.57(e) Warnings)
“BOXED WARNINGS”
FDA Commissioner has stated that the
Agency reserves boxed warnings only for
the most serious warnings and is a
“dramatic” step taken only if a new safety
issue alters the risk-benefit ratio.
FDA GUIDANCE CRITERIA
FOR BOXED WARNINGS
None exist. FDA has never issued a
guidance document relevant to when
or how it requires a boxed warning.
SOURCE OF EVIDENCE
RELIED UPON BY THE FDA
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•
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Post-market reporting
Clinical studies during the NDA
Clinical studies after marketing
Epidemiological surveys
CRITICISMS OF BOXED
WARNINGS
• Why one drug and not others?
• Are dose differences considered?
• How many deaths per patient use are
required?
• Is there consideration of alternative
treatments (safety, efficacy, cost)?
• Why isn’t public comment requested?
• Why no established criteria?
FREQUENCY OF BOXED
WARNINGS
One study found that 206 drugs in the
PDR in 1995 had boxed warnings, many
with more than one warning.
(Beach et al, 53 FDLJ 4/03 (1998).
FREQUENCY OF BOXED
WARNINGS
Another study: Of 548 drugs approved
between 1975 and 1999, 56 (10.2%) either
acquired a black box warning after
marketing or were withdrawn.
(Lasser et. al, 287 JAMA. 2215 (May, 1 2002)
PAIN MANAGEMENT DRUGS
WITH BOXED WARNINGS
•
•
•
•
•
•
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Clonidine
Fentanyl transmucosal (Actiq)
Fentanyl Oralet
Methadone
OxyContin
Propoxyphene
Toradol
NEW DRUG QUESTIONS
• Are drugs approved too rapidly?
• Should newly approved drugs be
used first line if established drugs
are available?
EFFECT ON FORMULARIES
Do black box warnings affect
formularies?
EFFECT ON HEALTH CARE
PROFESSIONALS
• Do they know of the warnings?
• Do they believe the warnings?
• Do the warnings affect prescribing
behavior?
FDA’S POSITION
FDA believes that the traditional risk
communication tools (e.g. current
package insert format, boxed warnings,
dear health care professional letters,
patient information from the pharmacy)
are ineffective.
EXAMPLES SUPPORTING
FDA’S POSITION
• NSAIDs withdrawn from market:
(Duract, Zomax, Oraflex, Suprol)
• Other Examples:
(Hisminal, Propulsid, Seldane,
Posicor, phenylpropanolamine,
Rezulin)
FDA’S POSITION
IS IT CORRECT?
PATIENTS
• Do they receive the warnings?
• Should they receive the warnings?
WHAT WOULD BE EFFECTIVE
RISK MANAGEMENT TOOLS FOR
PATIENTS?
• Revised package insert?
• Mandatory written patient information?
• Written informed consent of patients prior
to prescribing?
• Improved reporting of adverse events?
• Restricted drug distribution?
• Restricted drug marketing?
• Others?
CONCLUSION