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1. Rapid Communication with Clinicians During EmergenciesRapid Communication with Clinicians During Emergencies
2. Rapid Communication with Clinicians During EmergenciesRapid Communication with Clinicians During Emergencies
3. Rapid Communication with Clinicians During EmergenciesRapid Communication with Clinicians During Emergencies
4. Bruce Gellin, MD, MPH
Deputy Assistant Secretary for Health
Director, National Vaccine Program Office
Department of Health and Human Services
5. The Vaccine Safety System
6. Department of Health and Human Services (HHS)Roles and Responsibilities for Vaccine Safety Activities National Vaccine Program Office (NVPO)
Coordinates federal vaccine safety activities, reporting to the Assistant Secretary for Health, and bridges federal vaccine safety activities with non-federal partners
CDC
Makes vaccine recommendation, conducts post-licensure surveillance for adverse events, explores individual variation in vaccine associated adverse events, and conducts risk communication activities to a broad range of groups.
FDA
Regulatory authority over vaccine licensure, manufacturing and usage and post licensure surveillance
HRSA
Operates the Vaccine Injury Compensation Program (VICP) with the Department of Justice and the US Court of Federal Claims
CMS
Vaccine safety studies in >65 year olds
AHRQ
Background rates of medical conditions
NIH
Conducts and supports basic research and clinical trials in areas important for vaccine safety
7. Vaccine Safety Activities Outside of HHS Department of Defense
Department of Veterans Affairs
State public health departments
Academic researchers
Vaccine manufacturers
Healthcare providers
Parent groups and advocacy organizations
Professional organizations
Institute of Medicine
Philanthropic organizations
8. Why H1N1 Vaccine Safety Monitoring is Important Strain change: like seasonal influenza vaccine
However, the vaccine will be given to millions of people over a short period of time
Important to discriminate between causal and coincidental adverse events following immunization
Public trust and confidence
9. HHS Vaccine Safety Monitoring Activities Broad Initiatives:
Federal Immunization Safety Taskforce (ISTF)
National Vaccine Plan
National Vaccine Advisory Committee (NVAC) Safety Working Group
Public engagement meetings
Pediatrics Supplement on vaccine safety
10. Federal Immunization Safety Taskforce Chaired by HHS Assistant Secretary for Health and HHS Assistant Secretary for Preparedness and Response
Includes multiple HHS agencies as well as representatives from DoD and VA
Enhanced coordination of federal vaccine safety science, practice, public engagement and risk communication
Recommendations incorporated into National Vaccine Plan
Drafted Federal Plans to Monitor Immunization Safety for a 2009 H1N1 Vaccination Campaign
11. H1N1 Vaccine Safety Monitoring Activities Enhancements to existing vaccine safety systems and development of new monitoring and surveillance systems:
Vaccine Adverse Event Reporting System (VAERS), CDC/FDA
Vaccine Safety Data Link (VSD), CDC
Centers for Medicare & Medicaid Services Databases, CMS
Post-Licensure Rapid Immunization Safety Monitoring (PRISM), HHS, FDA & CDC
Defense Medical Surveillance System (DMSS), DoD, Department of Veterans Affairs Databases, VA
Emerging Infections Program (EIP), CDC
Real-Time Immunization Monitoring System (RTIMS), CDC
Indian Health Service Resource and Patient Management Database, HIS
Clinical Immunization Safety Assessment (CISA), CDC
Vaccines and Medications in Pregnancy Surveillance System (VAMPSS), BARDA
12. Development of New Systems – PRISM Post-Licensure Rapid Immunization Safety Monitoring (PRISM)
Collaboration between HHS, Harvard Pilgrim Health Center (HPHC), American’s Health Insurance Plans (AHIP), and the Public Health Informatics Institute (PHII)
Uses health plan data to actively monitor adverse events following immunization
Eight states will supply immunization histories from their registries to supplement health plan immunization records
13. Development of New Systems – PRISM cont. Approximately 15% of the US population under total surveillance
Approximately 10-20 million of which will be enhanced by state registry data
14. Coordinated Review of Monitoring Data On July 27, 2009, the National Vaccine Advisory Committee recommended consideration of a committee to perform “a transparent and independent review of vaccine safety data as it accumulates” http://www.hhs.gov/nvpo/nvac/H1N1SubgroupRecommendationsVSMJuly2009.html
In response, a vaccine safety risk assessment working group of the National Vaccine Advisory Committee is in the process of being formed
All federal H1N1 vaccine monitoring activities are coordinated by the Immunization Safety Task Force
15. Influenza A (H1N1) 2009 Monovalent Vaccines[H1N1 Vaccines] Theresa M. Finn, Ph.D
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research
Food and Drug Administration
16. Overview
Seasonal Influenza vaccines
Yearly formulation change
“Strain change” supplement
H1N1 vaccine licensure
H1N1 vaccines
17. U.S.-licensed Seasonal Influenza Vaccines Inactivated, intramuscular
Sanofi pasteur: Fluzone (>6 months)
Novartis: Fluvirin (>4 years)
CSL: Afluria (>18 years)
IDB-GSK: FluLaval (>18 years)
GSK: Fluarix (>18 years)
Live Attenuated, intranasal
MedImmune: FluMist (2-49years)
18. U.S.-licensed Seasonal Influenza Vaccines Trivalent
Influenza A (H1N1)
Influenza A (H3N2)
Influenza B
Yearly consideration of optimal strains: WHO/CDC/FDA Advisory Committee
Yearly “strain change supplement” to FDA
19. U.S.-licensed Seasonal Influenza Vaccines: Strain change Supplement Each yearly strain change:
Same egg based licensed manufacturing process
Same in-process controls at multiple stages of manufacture
Same lot release requirements
No additional clinical data (inactivated vaccines), limited clinical (safety) data (live attenuated)
20. H1N1 Vaccine Licensure U.S.-licensed manufacturers:
Strain change supplement to existing license
21. H1N1 Vaccines: Strain Change Supplements
Same egg based manufacturing process as licensed seasonal vaccines
Same in-process controls as licensed seasonal vaccines
Same lot release requirements as licensed seasonal vaccines
Same clinical data requirements as licensed seasonal influenza vaccines
22. H1N1 Vaccines September 15, 2009 FDA approved:
Inactivated:
Influenza A (H1N1) 2009 Monovalent Vaccine
Sanofi pasteur, Inc.
Novartis Vaccines and Diagnostics, Ltd.
CSL Ltd.
Live:
Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal
MedImmune LLC
23. H1N1 Vaccines Licensed for use in the same populations as each manufacturer’s seasonal influenza vaccine:
Sanofi pasteur: > 6 months of age
Novartis: > 4 years of age
CSL: >18 years of age
MedImmune: 2-49 years of age
Do not contain adjuvants
24. Clinical Studies Manufacturer and NIH sponsored
Immunogenicity
Safety
Optimal dose
Optimal number of doses
Optimal schedule
25. H1N1 Dosing regimen <9 years of age 2 doses
>10 years of age one dose
Supported by preliminary data from NIH and manufacturer sponsored studies
Adults >18 years: 1 dose
Children 10-17 years: 1 dose
Children 6m-9 years: 2 doses
26. H1N1 Vaccines Summary licensed monovalent H1N1 vaccines
Same populations as licensed seasonal
Same manufacturing process and testing as seasonal
27. CDCClinician Outreach and Communication Activity: H1N1 Vaccine Safety
Discussion of Clinical Trials to Support Use of the Monovalent H1N1 Vaccine
Emphasis on Safety
Sept 30, 2009
Richard L. Gorman, MD
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
National Institutes of Health
28. Outline NIAID Monovalent H1N1 vaccine trials
Policy Focus
7 Ongoing protocols
3 adult studies: unadjuvanted
2 pediatric studies: unadjuvanted
1 pregnancy study: unadjuvanted
1 adult study: adjuvanted
Safety Oversight
29. NIAID trials “Policy Focus” Help inform policy, “gap” areas
accelerate availability of 1 vs. 2 dose data in different populations
administration with seasonal influenza vaccine
use of different adjuvanted products
mixing stockpiled vaccines and adjuvant
Data not intended to support licensure
Complimentary to company planned trials
Safety in General and Special populations
young infants
pregnant women
immunocompromised
30. NIAID H1N1 Vaccine Trials First 3 protocols:
1 vs. 2 doses of unadjuvanted CSL vaccine in healthy adults: enrollment complete ~ 400
1 vs. 2 doses of unadjuvanted SP vaccine in healthy adults: enrollment complete ~ 400
co- vs. sequential administration of TIV and H1N1 vaccine in adults: enrollment complete ~ 800
Next 2 protocols
1 vs. 2 doses of unadjuvanted SP vaccine in healthy children: enrollment complete ~ 600
co- vs. sequential administration of TIV and H1N1 vaccine in children: enrollment complete ~ 600
31. NIAID H1N1 Vaccine Trials 2 protocols presently enrolling
Mixing and Matching Adjuvant and Antigen from different companies:
vaccines: CSL and sanofi pasteur H1N1 vaccine
adjuvant: GSK’s AS03
mixed prior to administration
protocol: 3.75µg +AS03, 7.5µg and 15µg +/- AS03
2 doses, 21 days apart
status: Sanofi pasteur/AS03: started 24 Sept 2009
Target enrollment ~ 750, presently enrolling
CSL/AS03 IND to follow
32. NIAID H1N1 Vaccine Trials 2 protocols presently enrolling
Monovalent H1N1 in Pregnant Women
Sanofi Pasteur, unadjuvanted, 1 dose, 2 dose 21 days apart
2nd and 3rd trimester women
Status: trial initiated 9 Sept 2009
Target Enrollment: ~120, presently enrolling
33. Monovalent H1N1 Vaccine Safety Oversight Safety Monitoring Committee
5 Members
All with infectious disease expertise
Additional Expertise: HIV, OB-GYN, Internal Medicine, Pediatrics, Biostatistics
2 Special Safety Consultants
Expertise: Large Clinical Trial Phamacovigilence, Adjuvant
10 to 30 Independent Safety Monitors:
local, independent, medical evaluator
34. Monovalent H1N1 Vaccine Safety Oversight Safety Monitoring Committee
Reviews all protocols prior to implementation for safety considerations
Reviews all adverse events, serious adverse events, subject withdrawals, subject terminations, protocols deviations
After analysis of safety, determines if a study should proceed, be modified or be stopped.
35. Monovalent H1N1 Vaccine Safety Oversight Conclusion and Take Home Message
At this time, the Safety Monitoring Committee has not recommended a modification or halting of any trial
The observed pattern of reactogenicity and adverse events is comparable with seasonal influenza vaccination
36. Acknowledgements DHHS
H1N1 vaccines for NIH trials under BARDA contract
FDA
CDC
Manufacturers
VTEU investigators
EMMES Corporation
SRI Birmingham
Fisher Bioservices
PPD
Independent Safety Committee members
NIAID and DMID colleagues
37. Monitoring the Safety of Influenza A (H1N1) 2009 Monovalent Vaccine Claudia Vellozzi, MD, MPH
Deputy Director
Immunization Safety Office
Division of Healthcare Quality Promotion
Centers for Disease Control and PreventionAtlanta, GA
38. Objectives To provide an overview of the CDC influenza A (H1N1) 2009 monovalent vaccine safety monitoring activities
To review the Vaccine Adverse Event Reporting System (VAERS)
To provide key resources for 2009 H1N1 vaccine safety for clinicians and public health officials
39. Overview of the CDC influenza A (H1N1) 2009 monovalent vaccine safety monitoring activities
40. Background When seasonal influenza vaccines are used according to licensed indication and usage information they are considered to be safe.
It is anticipated that the safety profile of licensed influenza A (H1N1) 2009 monovalent vaccine (2009 H1N1 vaccine) will be similar to seasonal influenza vaccines.
Serious adverse events after vaccination are uncommon.
Vaccine safety monitoring is an important component of the 2009 H1N1 response.
41. Background Review of adverse events following TIV among adults reported to VAERS from 1990-2005 (15 years)*
Approx 750 million doses distributed
Overall adverse event reporting rate of 24 per million TIV vaccinations
3.4 serious adverse events/million TIV vaccinations**
reporting rates have been fairly constant over time and no new safety concerns emerged following this comprehensive review
*Vellozzi, et al (2009)
42. Goals for 2009 H1N1 Vaccine Safety Monitoring Identify clinically significant adverse events following receipt of 2009 HINI vaccine in a timely manner
Rapidly evaluate serious adverse events following receipt of 2009 H1N1 vaccine and determine the public health importance
Evaluate if there is a risk of Guillain-Barré syndrome (GBS) associated with the 2009 H1N1 vaccine
Communicate vaccine safety information in a clear and transparent manner to healthcare providers, public health officials, and the public
43. Vaccine Adverse Event Reporting System (VAERS) VAERS: Voluntary reporting system jointly managed by CDC and FDA
Signal detection
National in scope
Flexible
Scalable
Encourages reports from healthcare providers and accepts reports from vaccinees, others
System enhancements underway
Increase in staffing to process VAERS reports more rapidly
44. VAERS Limitations Usually cannot assess causality
Variable quality of data
No unvaccinated comparison group
Denominator data lacking
Under-reporting (voluntary, passive reporting)
Variation of reporting: Stimulated reporting can occur during times of heightened awareness (e.g. Media attention, serious event occurs, MMWR release, other)
45. Vaccine Safety Datalink (VSD) Eight managed care organizations representing approximately 9 million US individuals
Sequential Analytical methods
Allows rapid assessment of pre-specified adverse events
Simultaneous analysis with appropriate comparison group
Chart confirmation is feasible
Requires accurate vaccination information within the managed care database
Outcome linked with exposure
46. VSD Limitations Up to a 2 week delay for available outcome data
Adverse events with longer risk windows add to delay of analysis
Power may not be sufficient for rare outcomes with limited vaccine use
Vaccination information within the MCO is necessary
47. Clinical Immunization Safety Assessment (CISA) Network Collaboration between CDC and 6 academic centers with vaccine safety experts
Provide vaccine safety clinical expertise in the evaluation of serious adverse events following 2009 H1N1 vaccination (e.g., assist with review of complex serious cases reported to VAERS)
48. Other Surveillance Systems Collaboration with DoD/CDC/FDA utilizing the Defense Medical Surveillance System (DMSS)
U.S. military personnel (~1.5 million active duty personnel)
Real Time Immunization Monitoring System (RTIMS)
Automated web-based active surveillance
Collaboration between CDC and Johns Hopkins School of Public Health
Post-Licensure Rapid Immunization Safety Monitoring (PRISM)
Collaboration National Vaccine Program Office (NVPO), FDA, and CDC
49. Guillain-Barré Syndrome (GBS) Immune-mediated acute demyelinating polyneuropathy affecting the peripheral nervous system
Estimated annual incidence rate: 1 case per 100,000 population
In 1976, a type of influenza vaccine was causally associated with GBS*
1 additional case per 100,000 persons vaccinated
Subsequent studies of influenza vaccines have found small or no increased risk of GBS
if there is a risk of GBS from seasonal influenza vaccines, it would be no more than ~1 additional case per million people vaccinated
50. GBS Active Case-Finding Emerging Infections Program (existing hospital based surveillance system)
Active GBS case finding (other adverse events as necessary)
Ascertainment of vaccination status
Identify risk factors for GBS (e.g., antecedant infection)
>50 million US population
10 states
American Academy of Neurology (AAN) collaboration
Increase VAERS awareness to enhance reporting
Enhanced GBS reporting in the EIP surveillance sites
GBS standard case definition being used*
51. CDC Support of Public Health Officials participating in H1N1 Vaccine Monitoring Collaboration between CDC’s Immunization Safety Office and Vaccine Safety Coordinators in 62 state, territorial and local health departments
Assist states with technical and epidemiologic investigation as needed
Regular communications with ASTHO, NACCHO, CSTE and other partners
53. What to Report to VAERS Report any clinically significant adverse event following immunization (www.vaers.hhs.gov)
Submit reports of concern even when not sure whether the vaccine caused the adverse event
Include as much information as possible (e.g., vaccination location, date, vaccine type, lot number and dose number)
Incomplete reports are accepted
Report as soon as possible but there is no time limit
54. How to submit a VAERS report 1) Online via a secure website at
https://vaers.hhs.gov
2) Download a form from: www.vaers.hhs.gov/pdf/vaers_form.pdf
Fax a completed form: 877-721-0366
Mail a completed VAERS form to: VAERS
P.O. Box 1100
Rockville, MD, 20849
3) VAERS assistance: 800-822-7967 or email: info@vaers.org
55. Clinician’s Role in Vaccine Safety Monitoring during the 2009 H1N1 vaccination campaign Properly store and administer vaccine
Screen for contraindications and precautions
Educate vaccinee (or caregiver) about risks and benefits of vaccine
Vaccine Information Statements (VIS)*
Use Influenza Vaccination Record (card)
Evaluate and treat patient if an adverse event occurs
Report clinically significant adverse events promptly to VAERS
https://vaers.hhs.gov
56. CDC Resources for 2009 H1N1 Vaccine Safety General Questions and Answers on 2009 H1N1 Influenza A Vaccine Safety http://www.cdc.gov/h1n1flu/vaccination/vaccine_safet_qa.htm
General Questions and Answers on Thimerosal http://www.cdc.gov/h1n1flu/vaccination/thimerosal_qa.htm
General Questions and Answers on Guillain-Barré Syndrome (GBS) http://www.cdc.gov/h1n1flu/vaccination/gbs_qa.htm
57. Summary2009 H1N1 Vaccine Safety Monitoring Established vaccine safety infrastructure will be utilized, enhancements in process
New collaborations being developed
CDC to provide support to states and territories during 2009 H1N1 vaccination program
Vaccine risk communication is an important component of the vaccine safety monitoring effort.
Clinicians play an important role in vaccine safety monitoring
58. Questions
59. Rapid Communication with Clinicians During EmergenciesRapid Communication with Clinicians During Emergencies