Transcript Pain James Witter MD, PhD Arthritis Advisory Committee July 29, 2002 (morning session)

Pain
Arthritis Advisory Committee
July 29, 2002 (morning session)
James Witter MD, PhD
Division of Analgesics, Anti-Inflammatory &
Ophthalmologic Drug Products
HFD-550
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Pain
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Symptom
Disease
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Meeting: Purpose
• By simplifying to concepts, an examination
of two main aspects of pain and its relief:
– How have analgesics been studied and labeled
to date?
– How should analgesics be studied and labeled
in the future?
• Ultimate goal is to “inform” analgesic
labels in a meaningful (pts and MD) way
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Acute Pain:
• A self-limiting condition.
• This informs how the drug should be:
– studied
– labeled
– used
• “off label” use has resulted in serious adverse events
and death with analgesic drugs in past
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Chronic pain:
• Daily or intermittent pain that
• occurs on or off medication and
• lasts:
– > 3 months (non-cancer patients)
– > 6 weeks (cancer pain)
• to not limit enrollment
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Who:
• Has never experienced pain?
• Thinks pain doesn’t hurt?
• Thinks pain doesn’t interfere with
activities?
• Thinks pain doesn’t impact your life?
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Analgesic Should:
• Relieve pain
• Improve function
• Improve quality of life
• and do so in a safe manner
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Labeling:
“Although label claims have legal and regulatory uses,
their central purpose is to inform prescribers and
patients about the documented benefits [and risk]
of a product”
Draft OA and RA guidance documents
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Arthritis-OTC Advisory Meeting:
March 25, 1998
• Morning portion
– onset of pain relief (fast-faster)
– study design for Rx/OTC analgesics
• Afternoon portion
– pain claim structure for acute and chronic pain
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March 25,1998:
Advisory questions
• Should pain claims be categorized as:
– for acute vs. chronic vs. unrestricted?
– by categories?
• neuropathic pain
– by subcategories?
• diabetic neuropathy
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March 25,1998
Advisory Questions
• Studies necessary to support analgesic claims?
– number and duration
– pain “models”
• What is ‘clinically meaningful’ benefit and how
should it be determined for acute and chronic
pain?
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Pain Claims: Future?
• Clinical
– Acute (ABC studies)
– Chronic (chronic studies)
• specific (i.e. osteoarthritis)
• general (replicates of three models)
• Mechanistic
– bridging studies
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Mechanistic Claim?
• Prevents neuroplasticity
• Reduces prostaglandin levels
• Reduces substance P in CSF
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Mechanisms of Total Pain Relief:
hypothetical model
Y
X
Z
Future Drugs
Opioids
NSAIDs
Pain
(chronic)
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Mathematics of Total Pain Relief?
• Hypothesis 1:
Any X + Any Z= 100%
• Hypothesis 2:
Any X + Any Z + Y = 100%
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Achieving Total Pain Relief?
• Plan 1
– improve safety of existing drugs
• Plan 2
– optimize use of existing drugs
– develop and approve new drugs (Y)
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Plan 3
Extra-Strength Pain Relief
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Ideas
Drugs
Research
Preclinical
Clinical
FDA
Label
Patients
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NIH-FDA Analgesic Drug
Development Workshop
March 13-14, 2002
James Witter MD, PhD
Division of Anti-inflammatory, Analgesic and
Ophthalmic drug products
HFD-550/CDER/FDA
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NIH-FDA Analgesic Workshop
Objectives
• To define unmet needs in pain
– management
– research
• To discuss how to
– harness emerging technologies
– improve the development, and FDA approval,
of new therapies
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NIH-FDA Workshop
Outcomes/Suggestions
• Separation of pain into acute and chronic
may miss addressing nervous system
“plasticity”
• No consensus pain metric exists but one is
needed to allow for comparisons and
pooling of results of analgesic trials
• New analgesics need to be evaluated as
supplementary medications on existing ones
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NIH-FDA Workshop
Outcomes/Suggestions
• Novel therapies needed to treat pain
mechanisms
• Translating scientific advances into
improved pain relief requires a cooperative
effort
• FDA guidance of 1992 needs revision
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Analgesic Drugs Guidance: 1992
• Discusses analgesic approaches of 1980’s
• Assumed revision would be necessary with
time
• Encourages “me too” type of drugs rather
than encouraging “me first” drugs that are
needed in the future.
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July 29, 2002
morning speakers
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•
•
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Christina Fang, MD (FDA)
Clifford Woolf, M.D., Ph.D (MGH)
Lee Simon, M.D. (FDA)
David Borenstein, M.D. (Georgetown)
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