Transcript Physician Labeling Rule Lisa Soule, M.D. DIVISION OF REPRODUCTIVE AND UROLOGIC PRODUCTS

Physician Labeling Rule
Lisa Soule, M.D.
DIVISION OF REPRODUCTIVE AND UROLOGIC PRODUCTS
§ 201.56 General Labeling
Requirements
 Labeling must:
 Contain a summary of essential scientific information for the
safe and effective use of the drug
 Be informative and accurate and neither promotional in tone
nor false or misleading
 Be based whenever possible on data derived from human
experience. No implied claims or suggestions of drug use
may be made if there is inadequate evidence of safety or
lack of substantial evidence of effectiveness
 Be updated when new information becomes available that
causes the labeling to become inaccurate, false, or
misleading
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Research shows…
 Health care providers:
 Use labeling primarily to find a specific item of information or
answer a specific question
 Found existing format difficult to use when looking for
specific information
 Wanted easy access to certain labeling sections that they
find more useful or important
 Would use labeling more if it included a short (maximum
length one-half page) synopsis
 Physician Labeling Rule (PLR) enacted to address
these needs
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PLR Improvements
 Emphasizes “Patient Counseling Information”
 Encourages adverse reaction (AR) reporting by
including contact information (toll-free number and
Internet address)
 Identifies and Dates “Recent Major Changes”
 Captures Boxed Warning, Indications, Dosage &
Administration, Contraindications, and Warnings &
Precautions
 Referenced in Highlights; margin mark in Full Prescribing
Information (FPI)
 Adds initial U.S. approval date
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Overview of PLR
 Highlights
 High level ½ page summary
 Cited or concisely summarized information,
accompanied by location in FPI to find more detail
 Table of Contents
 Reorders and reorganizes sections
 Frequently referenced information moved forward
 Safety information remains consolidated
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Highlights
 Concise summary of information in FPI
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Boxed Warning
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Contents and FPI
Boxed Warning
10 Overdosage
1 Indications & Usage
11 Description
2 Dosage & Administration
12 Clinical Pharmacology
3 Dosage Forms & Strengths
13 Nonclinical Toxicology
4 Contraindications
14 Clinical Studies
5 Warnings & Precautions
15 References
6 Adverse Reactions
16 How Supplied/Storage &
Handling
7 Drug Interactions
8 Use in Specific Populations
9 Drug Abuse & Dependence
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17 Patient Counseling Information
Format Changes
 Warnings and Precautions consolidated
 Formerly in Precautions, now new sections
 Drug Interactions
 Use in Specific Populations
 Patient Counseling Information
 Formerly optional, now required
 Clinical Studies
 Nonclinical Toxicology
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Contraindications and Boxed Warning Sections
 Contraindications
 Risk from use clearly outweighs any possible therapeutic benefit
 Known hazards only
 Hormonal contraceptive labels list about 15 contraindications
 Boxed Warning
 AR so serious that it must be considered in assessing the risks
and benefits of using a drug
 AR can be prevented or reduced in frequency or severity by
appropriate use of the drug
 Currently, only boxed warning on hormonal contraceptives
concerns smoking and increased risk of cardiovascular events
 Other, bolded warnings, appear variably in labels
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Adverse Reaction Section
 Definition of adverse reaction: “reasonably associated
with use of a drug” means that there is some basis to
believe there is a causal relationship between the drug
and occurrence of the AR
 Identify most important ARs
 Most common (>10% and 2x placebo)
 ARs leading to intervention (discontinuation, dose
change)
 Avoid “laundry lists” (low frequency ARs without clear
association with drug)
 Currently, hormonal contraceptive labels usually list both
“class” ARs and those noted in trials for the specific drug
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Adverse Reaction Section
The AR section is intended to be updated as new
information is obtained.
Sources of information include
 Controlled trials or epidemiological studies after
marketing approval
 Analyses of postmarketing adverse events
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Clinical Studies Section
 A newly required section
 Description of study design – may facilitate translation of
results
 Major design characteristics (e.g., blinding, controls,
duration, randomization, etc.)
 Treatment arms (if applicable), extent of exposure
 Study population (e.g., inclusion/exclusion criteria,
demographic characteristics, clinically relevant
baseline values)
 Methods that may have facilitated compliance (e.g.,
daily diaries, frequent contact with investigators)
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Opportunities
 The PLR initiative offers new opportunities to provide
more informative labeling
 New Patient Counseling Information section
 Newly required Clinical Studies section may help in
translation into the “real world”
 New rules for safety sections may help focus on most
relevant safety issues and allow for timely updating as
new information is obtained
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