Interim Report OTIS

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Interim Report OTIS North American
Isotretinoin Information and Survey Line
Toll-Free Number 1-866-626-6847 Website
www.otispregnancy.org

• FDA Advisory Committee Meeting
• Accutane Risk Management Program
• Gaithersburg, Maryland
• February 26, 2004

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Acknowledgements

• Funded by the Centers for Disease Control and
  Prevention in partnership with the Association of
  American Medical Colleges
• OTIS Survey Team
• Principal Investigator
• John Carey (University of Utah)
• Coordinator
• Julia Robertson (Utah Department of Health)
• OTIS Development and Review Teams
• Tina Chambers (University of California San
  Diego)
• Gideon Koren (Toronto Hospital for Sick
  Children)
• Sharon Lavigne (University of Connecticut)
• Richard Miller (University of Rochester)
• Janine Polifka (University of Washington)
• Cynthia Moore (CDC, Technical Monitor)

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Organization of Teratology Information Services
(OTIS)

• Non-profit, North American network of 19 state or
  regional Teratology Information Services (TIS)
• Provides up-to-date information regarding the
  effects of drugs and chemicals on the human
  embryo and fetus via free-of-charge telephone
  consultations
• Receives approximately 100,000 calls per
  year--half of the calls received initiated by
  patients (or the general public), half from
  health care professionals

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Organization of Teratology Information Services
(OTIS)

• OTIS is organized exclusively
• to stimulate and encourage research, education,
  and the dissemination of knowledge in the field
  of Teratology
• to improve the abilities of TISs to provide
  accurate and timely information about prenatal
  exposures, with the overall objective of
  preventing birth defects and improving the public
  health

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OTIS Recommendations for Use of
Isotretinoin, 2002

• Increased regulatory safeguards using the
  thalidomide S.T.E.P.S. program as a template to
  include
• Mandatory enrollment and compliance of
  physicians, pharmacists and patients in the
  program
• Mandatory participation of patients, prescribing
  physicians, and pharmacies in a single,
  independent and uniform registry
• Increased patient accessibility to the use of two
  reliable forms of contraception
• Continued educational activities provided for
  physicians, pharmacists and patients

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OTIS Recommendations for Use of
Isotretinoin, 2002

• Availability strictly limited to women who meet
  the clinical criteria for severe recalcitrant
  cystic acne
• Prescribing strictly limited to dermatologists
  who have enrolled in and agreed to comply with
  the S.M.A.R.T. program
• More effective and comprehensive contraceptive
  counseling
• Tollfree number and website on all packaging for
  direct access to risk assessment and counseling
• Continued evaluation of the effectiveness of this
  program and modification if necessary

The Subcommittee on Oversight and
Investigations, The Committee on Energy and
Commerce, United States House of Representative,
12/11/02
http//energycommerce.house.gov/107/hearings/12112
002Hearing755
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Previous Accutane Research OTIS

• In 2000, the California TIS contributed to a
  study of 14 women whose pregnancy was
  inadvertently exposed to isotretinoin, reflecting
  a failure of the pregnancy prevention program

(Chambers, C., et al., Accutane-Exposed
Pregnancies California, 1999. MMWR 49 28-31,
2000).
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• OTIS Experience with Isotretinoin Exposures
• during Pregnancy, 2001 - 2003

Year Total of Isotretinoin Callers Isotretinoin Exposed Callers (US) of TIS Reporting Isotretinoin Exposed Callers (Canada) of TIS Reporting
2003 37 29 11 8 2
2002 32 24 16 8 2
2001 39 24 20 15 2
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• OTIS Experience with Isotretinoin Exposures
• during Pregnancy, 2001 - 2003

Year Total of Isotretinoin Callers Isotretinoin Exposed Callers (US) of TIS Reporting Isotretinoin Exposed Callers (Canada) of TIS Reporting
2003 37 29 11 8 2
2002 32 24 16 8 2
2001 39 24 20 15 2
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OTIS Isotretinoin Survey

• Enrollment
• Women who called a TIS about an isotretinoin
  exposure during pregnancy enrolling through
  Sept. 2004
• Methods
• Detailed, structured interview by a research
  specialist participant followed until the
  outcome is known
• Study Objective
• To identify barriers to the successful
  implementation of the components of the
  pregnancy risk management program

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OTIS Isotretinoin Survey Assessing the Goals

• Goals of the S.M.A.R.T. Program
• To prevent pregnancy in women who are taking
  isotretinoin
• To prevent embryonic exposure to isotretinoin in
  women who are already pregnant
• Case histories from the OTIS survey

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Case History Pregnancy Exposure

• Goal To prevent pregnancy in women who are
  taking isotretinoin
• Ms. A., 30s, reported taking isotretinoin
  samples
• Exposure during weeks 3 to 7 of gestation
• Birth control method discontinued one month prior
  to starting isotretinoin and misinterpreted
  OB-GYNs statement about ability to conceive
  afterwards
• Prescribing dermatologist did not order pregnancy
  tests or confirm two forms of contraception
• Pregnancy continuing fetal status unknown

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Case History Pregnancy Exposure

• Goal To prevent embryonic exposure to
  isotretinoin in women who are already pregnant
• Ms. Z., teenager, reported taking isotretinoin
• Exposure during weeks 5 to 6 of gestation
• Denied possibility of pregnancy to dermatologist
  despite positive pregnancy test
• Given prescription by dermatologist without
  additional pregnancy testing
• Pregnancy continuing fetal status unknown

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Case History Summary

• Case histories illustrate several missed
  opportunities for prevention of exposure to
  isotretinoin during pregnancy
• Errors arise from multiple sources such as
  miscommunication between the health care
  provider and patient, misinterpretation of
  information by the health care provider, and
  denial of risk by the patient
• Lack of adherence to required components of the
  risk management program removed safeguards that
  might have prevented these exposures

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OTIS Isotretinoin Survey Interim Results

• Enrollment
• United States 11 women (Apr. 2003 - Feb. 2004)
• Canada 12 women (Feb. 2001 - Feb. 2004)
• Key differences in isotretinoin risk management
  programs in the United States and Canada
• United States S.M.A.R.T. program begun Apr. 2002
• Canada P.P.P. continued

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Use of Isotretinoin Interim Results

• In response to several questions about use of
  isotretinoin, survey participants
• Described their skin problem as cystic or nodular
  acne
• S.M.A.R.T. (36) P.P.P. (33)
• Recalled that their doctor had diagnosed their
  condition as cystic or nodular acne
• S.M.A.R.T. (20) P.P.P. (9)
• Recalled treatment with oral antibiotics before
  isotretinoin was prescribed
• S.M.A.R.T. (82) P.P.P. (57)

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S.M.A.R.T. Elements

• Women must have two negative pregnancy tests
  before receiving a prescription
• Women must use two forms of birth control
  simultaneously, starting one month before
  receiving a prescription
• Women must receive a pregnancy test each month
  before refilling their prescription
• Pharmacists must only fill prescriptions that
  bear a yellow qualification sticker

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S.M.A.R.T. Elements 1 Interim Results

• Women must have two negative pregnancy tests
  before receiving a prescription
• RESPONSES FROM OTIS SURVEY
• Women reporting that they had a second pregnancy
  test during their menstrual period before
  beginning isotretinoin
• S.M.A.R.T. (27) P.P.P. (33)
• CONCLUSION
• For the S.M.A.R.T. program, it appears that 73
  of women surveyed were not screened using two
  pregnancy tests as required

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S.M.A.R.T. Elements 2 Interim Results

• Women must use two forms of birth control
  simultaneously, starting one month before
  receiving a prescription
• RESPONSES FROM OTIS SURVEY
• Women surveyed who said they were using two
  forms of birth control
• S.M.A.R.T. (36) P.P.P. (8)
• CONCLUSION
• 64 of the women surveyed indicated they were
  not following the S.M.A.R.T. requirement to use
  two forms of birth control

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S.M.A.R.T. Elements 3 Interim Results

• Women must receive a pregnancy test each month
  before refilling their prescription
• RESPONSES FROM OTIS SURVEY
• Women in the study reporting that they had
  monthly pregnancy testing during the course of
  therapy
• S.M.A.R.T. (36) P.P.P. (83)
• CONCLUSION
• For the S.M.A.R.T program, it appears that 64
  of women were not screened for pregnancy monthly
  as required

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S.M.A.R.T. Elements 4 Interim Results

• Pharmacists must only fill prescriptions that
  bear a yellow qualification sticker
• RESPONSES FROM OTIS SURVEY
• U.S. women who recalled seeing a yellow sticker
  on the prescription they took to the pharmacy
• S.M.A.R.T. (30)
• CONCLUSION
• For more than two-thirds of the women surveyed,
  there is doubt about compliance with use of the
  S.M.A.R.T. program yellow qualification sticker

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Monitoring Compliance Interim Results

• In response to participation in any of the
  manufacturers surveys, for the U.S. and Canada
  combined
• 13 of women surveyed reported that they had
  participated in the Accutane Survey
• 65 reported that they did not participate in any
  of the manufacturers surveys
• 18 did not know if they had participated

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Survey Strengths and Limitations

• Strengths
• OTIS has extensive experience in communicating
  with women about their reproductive concerns
• Survey used a detailed, structured interview
  instrument
• Most U.S. interviews were completed within 3
  months of exposure and before the status of the
  fetus was known
• Limitations
• Small numbers limit interpretation
• Estimates based on womens recall of events
• Women who call a TIS and agree to participate in
  a survey might not be representative

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Preliminary Conclusions

• Consistent with U.S. data reported prior to
  institution of the S.M.A.R.T. program
• Show similar rates of non-compliance in the U.S.
  with the S.M.A.R.T. program and in Canada with
  the P.P.P.
• Demonstrate that preventable exposures continue
  to occur due to non-compliance with current
  requirements of the S.M.A.R.T. program
• Provide important qualitative data that may
  identify risk factors for exposure and help
  design more effective prevention strategies

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Interim Report OTIS North American
Isotretinoin Information and Survey Line
Toll-Free Number 1-866-626-6847 Website
www.otispregnancy.org

• FDA Advisory Committee Meeting
• Accutane Risk Management Program
• Gaithersburg, Maryland
• February 26, 2004

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OTIS Recommendations for Use of
Isotretinoin, 2002
The Subcommittee on Oversight and
Investigations, The Committee on Energy and
Commerce, United States House of Representative,
12/11/02
http//energycommerce.house.gov/107/hearings/12112
002Hearing755
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Organization of Teratology Information Services
(OTIS)