review of tysabri risk minimization action plan (riskmap) diane wysowski, ph.d. division of drug...
Post on 29-Dec-2015
221 Views
Preview:
TRANSCRIPT
Review of Tysabri Risk Minimization Action Plan
(RiskMAP) Diane Wysowski, Ph.D.
Division of Drug Risk EvaluationOffice of Drug Safety
Peripheral and Central Nervous System Drugs Advisory Committee Meeting
March 7-8, 2006
2
Presentation Outline
• Briefly review main features of:
-Tysabri RiskMAP goals and methods
-Tysabri Registry for PML surveillance
-Tysabri Observational Study
• Present issues/questions re: above
3
Sponsors’ Tysabri RiskMAP Goals
• To promote informed risk-benefit decisions re: Tysabri use in treatment of MS pts.
• To minimize risk of PML
– contraindicated in immunocompromised patients
• To minimize health consequences of PML (death/disability) thru early diagnosis
4
Tysabri Enrollment Process
• Medication Guide provides pt. info. re: Tysabri, PML (death/disability) risk, other safety concerns, instructions to report “any new or continuously worsening neurological symptoms”
• Mandatory enrollment of prescribers and patients through Enrollment form
5
Tysabri Enrollment Process
• Mandatory Patient–Physician Acknowledgment Form (Informed Consent) completed and signed by patient and physician
• Tysabri forms and Rx sent to sponsor
6
Patient-Physician Acknowledgment Form
Physician acknowledges / signs:• Has read full prescribing information• Is aware of PML risk (disability/death) • Has discussed risk / benefits with pt.• Is prescribing for relapsing MS• Confirms pt. has no contraindications• Has told pt. to report new or worsening
neurological symptoms• Is enrolling in Tysabri Registry
7
Patient-Physician Acknowledgment Form
Patient acknowledges / signs:
• Has read Medication Guide
• Is aware of PML risk (disability/death)
• Has discussed risks / benefits with M.D.
• Understands need to report to M.D. new or worsening neurological symptoms
• Is enrolling in Tysabri Registry
8
Tysabri Authorization
Sponsors plan to:
• Enter patient and prescriber M.D. information into Tysabri Registry
• Match patient to authorized infusion center
• Notify infusion center of pt. authorization to receive Tysabri
• Provide center with Pt. Authorization No.
9
Tysabri Distribution
• Tysabri shipped from “centralized distribution system”
-one distributor
- ≤12 specialty pharmacies
-shipped only after receiving patient authorization code from sponsors
10
Tysabri Administration
• Tysabri administered only at trained / authorized infusion ctrs.:
-hospital clinic -stand alone clinic
-M.D. office• Sponsors estimate ~2,000
authorized infusion centers
11
Tysabri Administration
Infusion Center Nurses To Confirm:• M.D. and pt. enrolled in Registry• Patient has MS (Patient Checklist)• Patient has Medication Guide and has read it (Checklist)• Pt. is not known to be immunocompromised by: HIV,
hem. cancers, organ transplants, anti-neoplastic and immunosuppressive drugs (Checklist)
• Pt. has not experienced any new or continuously worsening neurological symptoms lasting over several days (Checklist)
• Dose administered is documented (Infusion log)
12
Tysabri Administration
• No specific contraindications of Tysabri with concomitant/recent use of:
-immune modulator drugs (e.g., interferon beta)
-systemic corticosteroids (e.g., methylprednisolone)
-other steroid and immune suppressant drugs
13
Tysabri Administration
• Patient Checklist gives examples of a few diseases and six drugs that induce immunocompromise
• Sponsors’ focus group wanted “all drugs and diseases that could induce an immunocompromised status clearly spelled out”
14
Education of Prescribers, Infusion Center Nurses
Sponsors propose to:• Deliver ongoing educational info. via
mailings, website, toll-free helpline, CME programs• Survey M.D.s and infusion center nurses: -knowledge of Tysabri’s PML risk -appropriate use conditions
15
Tysabri Registry / Pt. Follow-Up
• Sponsors will query prescribing M.D. every 6 months for:
-pt. continuation of Tysabri
-any PML cases
• Length of patient f/u not specified
16
PML Cases
Sponsors plan:
• Special assessment (questionnaire, MRI, CSF JC virus) of suspected PML cases for early diagnosis of PML and incidence rate
• Submission of data for uncertain diagnoses to external PML expert
• Qualitative analyses of PML risk factors
17
Issue: Maximizing Benefit, Minimizing Risk of Tysabri
Should there be Tysabri restriction:
• By MS disability severity?
• By failure on other MS therapies?
18
Issue: Minimizing PML Risk
Should there be:
• Tysabri contraindication for concomitant and recent use of:
-immune modulator drugs,
-systemic corticosteroids, and
-immune suppressant drugs?
19
Issue: Patient Assessment
Should there be:
• Periodic M.D. REassessment and REauthorization of patients to receive Tysabri? If so, how frequently?
• Assessment by M.D. (vs. nurse) of neurological symptoms and immune suppression before Tysabri administration?
• Inclusion on Pt. Checklist of all diseases and drugs that can induce an immunocompromised state?
20
Issue: Tracking Tysabri Vials
Should there be:
• One to one patient to vial distribution (each vial associated with a patient) for tight control of Tysabri distribution and tracking?
21
Issue: Patient Follow-up
Aided by:
• Real time collection of Tysabri administration, discontinuation, and reasons for discontinuation?
• Follow-up of patient deaths thru the National Death Index and collection of death certificates?
22
Tysabri Observational Study
Tysabri observational study (subset of 3,000 U.S. Tysabri Registry patients) followed for up to 5 years after starting Tysabri for:
-serious non-PML opportunistic infections
-cancer
-overall safety profile
23
Evaluation Re: Tysabri Observational Study
• Ascertainment of deaths and causes thru National Death Index and death certificate collection
• Inclusion of all patients in Tysabri Registry
• Problems in interpretation of etiology
-no non-exposed MS controls
-availability of population control data
24
SUMMARY
Issues presented should be carefully considered to maximize Tysabri benefits and minimize PML risk.
25
Tysabri ODS RiskMAP Review Team
• Mark Avigan, M.D., C.M., Director, DDRE• Allen Brinker, M.D., M.P.H., Epidemiology TL, DDRE• Jonca Bull, M.D., Acting Deputy Director, ODS-IO• Gerald Dal Pan, M.D., M.H.S., Director, ODS-IO• Mary Dempsey, Project Management Office, ODS-IO • Andrea Feight, D.D.S., M.P.H., Epidemiologist, DSRCS• Charlene Flowers, R.Ph., Safety Evaluator, DDRE• Laura Governale, Pharm.D.,M.B.A., Drug Utilization TL, DSRCS• Claudia Karwoski, Pharm.D., Scientific Coordinator, ODS-IO• Cindy Kortepeter, Pharm.D. Safety Evaluator TL, DDRE• Toni Piazza-Hepp, Pharm.D., Acting Deputy Director, DSRCS• Judy Staffa, R.Ph., Ph.D., Epidemiologist TL, DSRCS • Diane Wysowski, Ph.D., Epidemiologist, DDRE
top related