Risk Management Options

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Risk Management Options

• Russell Ellison, MDChief Medical OfficerVice
  President, Medical Affairs
• Roche Laboratories, Inc.

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Accutane and Pregnancy

• Accutane use is increasing
• The pregnancy rate is declining
• The pregnancy rate in women on Accutane is about
  80-90 less than for those with normal
  contraceptive use (0.3 vs. 1-5)
• For every 1000 women treated with Accutane,
  pregnancy has not occurred in 997

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The absolute goal is the prevention of pregnancy
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HOWEVER

• While an individuals risk of pregnancy is
  decreasing, the total public health burden has
  not.
• i.e the absolute number of exposed pregnancies
  has not decreased

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To Prevent Pregnancy

• Every patient has to avoid pregnancy every day of
  therapy
• 1st trimester teratogens require patient not to
  be pregnant at start of treatment or to become
  pregnant during treatment as well
• later trimester teratogens require the physician
  to avoid prescription during pregnancy

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FDA OPTIONS TPPP PLUS Option 1.. Mandatory
registration of all female patients External data
sources monitoring program impact Option 2 1
plus No dispensing unless pharmacist confirms a
documented negative pregnancy prevention
test Option 3 2 plus Pharmacist confirms that
appropriate patient compliance with contraceptive
practices, drug sharing and blood donation
guidelines has been documented Option 4 3
plus Pharmacists would have to be trained,
registered, and authorized before allowed to
dispense Accutane
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every woman must avoid pregnancy every day
Mandatory Programs

• Try to obtain compliance through conditional
  access to the drug, does not achieve active
  participation through motivation and knowledge
• Require a single channel of distribution and
  access to the drug

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every woman must avoid pregnancy every day
Mandatory Programs

• Stress completeness of documentation of
  compliance (in public at the pharmacy counter),
  not effectiveness of practice
• Enforce a population standard for all patients
  not an optimal program for the individual

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every woman must avoid pregnancy every day
Mandatory Programs

• Through the manufacturer, to be implemented by
  the pharmacist
• require additional qualifications or conditions
  from the prescriber to be fulfilled for the
  dispensing of a drug beyond the States licensure
  of the prescriber and/or the State Medical
  Boards regulations

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every woman must avoid pregnancy every day
Mandatory Programs

• The pharmacist is now being asked to control the
  behavior of the doctor and the patient
• Is this appropriate?
• Is this feasible?

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FDA OPTIONS TPPP PLUS Option 1.. Mandatory
registration of all female patients External data
sources monitoring program impact Option 2 1
plus No dispensing unless pharmacist confirms a
documented negative pregnancy prevention
test Option 3 2 plus Pharmacist confirms that
appropriate patient compliance with contraceptive
practices, drug sharing and blood donation
guidelines has been documented Option 4 3
plus Pharmacists would have to be trained,
registered, and authorized before allowed to
dispense Accutane
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every woman must avoid pregnancy every day
Mandatory Registration

• Does not reduce the risk of pregnancy
• Only benefit is a denominator of 100
• Coercive condition of drug is public registry
  vs. private consent
• Considerable risk of poor follow-up (response)
  and reliability and chance of erroneously low
  pregnancy and compliance rates

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every woman must avoid pregnancy every day
Mandatory Programs

• Common feature of all four options
• Excessive burden on physicians and patients with
  no perceived individual benefit
• Will produce an indiscriminate barrier to access

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Risk Management Programs PregnancyWhat
experience do we have?

• Accutane PPP voluntary, initiated 1989
• evaluated, published, publicly reviewed
• pregnancy rate known with tight CI
• successful at reducing individual risk from
  normal contraceptive practice
• 200,000 women treated per year
• young healthy patients
• well known unique drug
• alternate channels available

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Risk Management Program - TPPP
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Risk Management Program-TPPP
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Risk Management Programs Pregnancy What
experience do we have?

• STEPS (Thalidomide) mandatory, introduced 1997
• basic design is publicly known
• no evaluation or review of results publicly
  available
• small population (majority are ill, older women)
• gt50 have malignancies
• alternate channels for patient access??

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• Based on what we know, and balancing
• likelihood of success
• risk of compromising current success
• risk of denying treatment to patients who would
  not become pregnant

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• To prevent pregnancy in women prescribed
  Accutane, mandatory programs
• are untested
• have unknown benefits over the T-PPP and
  unquantifiable risks which will be difficult to
  ascertain and reverse

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every woman must avoid pregnancy every day

• Pregnancy Prevention for women taking Accutane is
  a shared responsibility of
• Roche
• Prescriber
• Pharmacist, nurse, reproductive health
  professional
• PATIENT
• The TPPP is the best method to assure active
  participation of all parties to prevent
  pregnancy, and has the optimal chance of success
  with least risk

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Roche is committed to the absolute goal of
pregnancy prevention and the continual
improvement of the TPPP