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The National Vaccine Advisory Committee (NVAC)
National Vaccine Advisory Committee (NVAC) Vaccine Safety Working Group
April 11, 2008
CDC’s Immunization Safety Office
Scientific Agenda Development
Karen R. Broder, MD
John K. Iskander, MD, MPH
Dixie E. Snider, MD, MPH
Immunization Safety Office
Office of the Chief Science Officer (OCSO), CDC
1
CDC’s Immunization Safety Office
Scientific Agenda Presentations: Overview
Topic |
Presenter |
Slide No. |
Opening Remarks |
Dr. Iskander |
2 |
Background Information |
Dr. Broder |
3—17 |
Draft Recommendations: Overview |
Dr. Broder |
18—23 |
Draft Recommendations: 5-Year Research Needs |
Dr. Broder |
24—33 |
Considerations for Prioritization |
Dr. Snider |
34—42 |
2
CDC’s Immunization Safety Office
Scientific Agenda Presentations
Topic |
Presenter |
Slide No. |
Opening Remarks |
Dr. Iskander |
2 |
Background Information |
Dr. Broder |
3—17 |
Draft Recommendations: Overview |
Dr. Broder |
18—23 |
Draft Recommendations: 5-Year Research Needs |
Dr. Broder |
24—33 |
Considerations for Prioritization |
Dr. Snider |
34—42 |
3
Department of Health and Human Services
Vaccine Safety Infrastructure
4
Immunization Safety Office Mission
- ISO mission: Assess the safety of vaccines administered to children, adolescents and adults
- ISO works closely with partners nationally and globally to develop, provide and support:
- High quality research and surveillance in the vaccine safety field to identify adverse events after vaccination and assess causality and risk factors
- Communication of this work in a clear and transparent manner
- Development of scientific methodology and standardized case definitions for adverse events after vaccination
5
Immunization Safety Office:
Research and Surveillance Infrastructure
- Vaccine Adverse Event Reporting System (VAERS)
- Jointly operated by CDC and FDA
- National early-warning passive surveillance system
- Identifies vaccine safety areas of potential concern and generates hypotheses
- Vaccine Safety Datalink (VSD) Project
- Collaboration between CDC and 8 managed care organizations
- Provides comprehensive medical and immunization histories for >5.5 million people annually
- Tests hypotheses suggested by signals from VAERS or other sources and conducts vaccine safety surveillance in near real-time
6
Immunization Safety Office:
Research and Surveillance Infrastructure(continued)
- Clinical Immunization Safety Assessment (CISA) Network
- Collaboration between CDC and six academic centers with vaccine subject matter experts
- Studies the pathophysiology of adverse events following immunization (AEFI)
- Studies risk factors including genetic associations for the development of AEFI
- The Brighton Collaboration
- Global collaboration
- Develops standardized case definitions
- Provides common “vocabulary” for vaccine safety research and surveillance
7
Inter-relationships across ISO
Research and Surveillance Components
8
Institute of Medicine (IOM)
Review and Recommendation for
ISO Research Agenda
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In February 2005, IOM recommended “a subcommittee of NVAC [National Vaccine Advisory Committee] that includes representatives of a wide variety of stakeholders… review and provide advice on the VSD research plan… the group should meet publicly and allow interested persons to observe the process and provide input through established mechanisms.”
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*Vaccine Safety Research, Data Access, and Public Trust, available at http://www.nap.edu/catalog/11234.html, accessed 7/30/07
9
Rationale for ISO Scientific Agenda
- Responsive to the 2005 IOM recommendation*
- Carrying out effective vaccine safety scientific activities requires integration across the ISO research and surveillance components
- Promotes scientific excellence and public trust, through transparency
- Contributes to vaccine safety science and other patient safety initiatives
*Vaccine Safety Research, Data Access, and Public Trust, available at http://www.nap.edu/catalog/11234.html, accessed 7/30/07
10
Objective and Scope of ISO Agenda
- Objective: to develop a comprehensive 5-year ISO Scientific Agenda with extensive expert input
- Scope: vaccine safety research, selected surveillance, and selected clinical guidance activities that
- Are part of ISO’s mission
- Are in ISO’s realm to lead
- Could be implemented during the next 5 years with infrastructure generally accessible to CDC
11
Overview of Scientific Agenda Development
- ISO/CDC developed a draft ISO Scientific Agenda
- Solicited external and internal input from scientists with diverse expertise
- Synthesized input to establish draft recommendations
- NVAC is facilitating a scientific review of draft ISO Scientific Agenda
- First meeting with NVAC Vaccine Safety Working Group on April 11, 2008
- ISO/CDC will respond to feedback from NVAC review process and finalize the ISO Scientific Agenda
12
CDC and National Vaccine Program Office (NVPO)
External Input Meetings for ISO Scientific Agenda
Input Group |
Description |
Meeting Date |
ISO external scientific consultants
|
CDC individual simultaneous consultation with 7 individual expert scientists and 7 liaisons |
May 10-11, 2007,
Atlanta, GA |
HHS and DoD agency and program scientists |
NVPO Interagency Vaccine Group (IAVG) meeting with 21 federal scientists outside ISO |
August 3, 2007,
Washington DC |
Non-federal vaccine scientists |
NVPO-sponsored meeting with 10 vaccine manufacturer representatives |
November 16,2007,
Washington DC |
13
Other Input for ISO Scientific Agenda
- Day-to-day partners
- ISO research and surveillance teams
- ISO Agenda Writing and Reviewing Group (formed 1/08)
- CDC immunization experts, including persons involved with the Advisory Committee on Immunization Practices (ACIP)
- Unsolicited input: review of selected ACIP statements, Institute of Medicine (IOM) reports, literature and other sources
- Public input: approaches will be discussed during the NVAC Vaccine Safety Working Group meeting on April 11, 2008
14
NVAC Safety Working Group Charge
- Undertake and coordinate a scientific review of the draft ISO Scientific Agenda
- Advise on:
- Content of ISO draft Scientific Agenda (e.g., are the topics on the Agenda appropriate? Should other topics be included?)
- Prioritization of scientific topics
- Possible scientific barriers to implementing the Scientific Agenda and suggestions for addressing them
15
Acknowledgements
- External, expert vaccine safety consultants
- Interagency Vaccine Group federal scientists
- Vaccine manufacturers’ representatives
- National Vaccine Program Office
- National Vaccine Advisory Committee
- Advisory Committee on Immunization Practices
- Centers for Disease Control and Prevention (CDC) immunization experts and stakeholders
- CDC’s Immunization Safety Office (ISO) research and surveillance partner scientists
- CDC/ISO Agenda Writing and Reviewing Group
- CDC/ISO and Office of the Chief Science Officer scientists and staff
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Resources
17
CDC’s Immunization Safety Office
Scientific Agenda Presentations
Topic |
Presenter |
Slide No. |
Opening Remarks |
Dr. Iskander |
2 |
Background Information |
Dr. Broder |
3—17 |
Draft Recommendations: Overview |
Dr. Broder |
18—23 |
Draft Recommendations: 5-Year Research Needs |
Dr. Broder |
24—33 |
Considerations for Prioritization |
Dr. Snider |
34—42 |
18
Summary of ISO Scientific Agenda
Draft Recommendations
- Respond to emerging issues and conduct core, required scientific activities
- Enhance vaccine safety public health and clinical guidance capacity in 7 areas
- Address 5-Year research needs
19
ISO Agenda Draft Recommendations
#1 Respond to emerging issues and conduct core, required scientific activities
- Monitor the safety of all newly licensed and Advisory Committee on Immunization Practices (ACIP) recommended vaccines and previously licensed vaccines with new recommendations
- Respond to new vaccine safety concerns and hypotheses, which are not always predictable
20
ISO Agenda Draft Recommendations
#1 Respond to emerging issues and conduct core, required scientific activities (cont.)
- Provide technical consultation to CDC immunization experts and other stakeholders for collaborative and multidisciplinary scientific activities
- Prepare to monitor vaccine safety in the event of a mass vaccination campaign or other vaccine safety emergency
21
ISO Agenda Draft Recommendations
#2: Enhance Vaccine Safety Public Health and Clinical Guidance Capacity in 7 Areas
Item |
Capacity Area |
A |
Infrastructure for Vaccine Safety Surveillance: Vaccine Adverse Event Reporting System (VAERS) |
B |
Infrastructure for Vaccine Safety Surveillance
and Research: Vaccine Safety Datalink (VSD) Project |
C |
Epidemiologic and Statistical Methods for Vaccine Safety |
D |
Laboratory Methods for Vaccine Safety |
E |
Genomics and Vaccine Safety |
F |
Case Definitions, Data Collection, and Data Presentation for Adverse Events Following Immunization |
G |
Vaccine Safety Clinical Practice Guidance |
22
ISO Agenda Draft Recommendations
#3 5-Year Research Needs (30 items)
Item |
5-Year Research Needs (30 items)
|
A |
Specific Vaccine Safety Questions (7 items) |
B |
Thematic Area: Vaccines and Vaccination Practices
(8 items) |
C |
Thematic Area: Special Populations (7 items) |
D |
Thematic Area: Clinical Outcomes (8 items) |
23
CDC’s Immunization Safety Office
Scientific Agenda Presentations
Topic |
Presenter |
Slide No. |
Opening Remarks |
Dr. Iskander |
2 |
Background Information |
Dr. Broder |
3—17 |
Draft Recommendations: Overview |
Dr. Broder |
18—23 |
Draft Recommendations: 5-Year Research Needs |
Dr. Broder |
24—33 |
Considerations for Prioritization |
Dr. Snider |
34—42 |
24
ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs:
General Principles
- Proposed 30 research needs for the next 5 years
- Specific vaccine safety questions (7 items)
- Scientific thematic areas (23 items)
- Some overlap of content in lists exists
- Study design not specified; factors to consider include demographic characteristics, underlying medical history and potential genetic risk factors
25
ISO Agenda Draft Recommendations
#3 5-Year Research Needs (30 items)
Item |
5-Year Research Needs (30 items)
|
A |
Specific Vaccine Safety Questions (7 items) |
B |
Thematic Area: Vaccines and Vaccination Practices
(8 items) |
C |
Thematic Area: Special Populations (7 items) |
D |
Thematic Area: Clinical Outcomes (8 items) |
26
ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs
Methods
Step |
Activity and Description
|
1 |
External input: 3 scientific meetings with experts and other sources (about 40 scientists excluding ISO staff) |
2 |
ISO synthesis of external inputs; determined if ideas met inclusion criteria
- ISO routinely leads topic
- ISO could implement a study in the next 5 years using
infrastructure accessible to CDC
- Vaccine routinely used in civilian population in next 5 years
|
3 |
Internal reviews: 3 separate reviews by ISO research partners and CDC immunization experts (about 40 scientists excluding ISO staff) |
4 |
ISO synthesis and adjudication from internal reviews |
27
ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs:
Tasks for NVAC Working Group Review
- Review the 4 proposed research areas of need
- For each, suggest
- Additions
- Modifications
- Deletions
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ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs:
A. Specific Vaccine Safety Questions (Hypotheses)
Item |
A. Specific Vaccine Safety Questions
|
A-I |
Are vaccines (e.g., influenza vaccines, meningococcal conjugate vaccine [MCV4]) associated with increased risk for Guillain-Barré Syndrome (GBS)? |
A-II |
Is live, attenuated influenza vaccine (LAIV) associated with
increased risk for asthma and/or wheezing, particularly in
young children or persons with history of wheezing? |
A-III |
Is exposure to thimerosal associated with increased risk for clinically important tics and/or Tourette syndrome? |
A-IV |
Are acellular pertussis vaccines associated with increased risk for acute neurological events, particularly hypotonic-hyporesponsive episodes (HHE)? |
29
ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs
A. Specific Vaccine Safety Questions (Hypotheses) (cont.)
Item |
A. Specific Vaccine Safety Questions (Hypotheses)
|
A-V |
Is immunization associated with increased risk for neurological deterioration in children with mitochondrial disorders? |
A-VI |
Is combination measles, mumps, rubella, and varicella (MMRV) vaccine associated with increased risk for febrile seizure and, if so, are there sequelae? |
A-VII |
Are varicella vaccines (varicella and MMRV) associated with increased risk for clinically important events related to varicella vaccine virus reactivation? |
30
ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs
Item |
B. Thematic Area: Vaccines and Vaccination Practices |
B-1 |
Bivalent human papillomavirus (bivalent HPV) vaccine (Cervarix™) |
B-II |
Zoster vaccine (Zostavax®) |
B-III |
Annual influenza vaccination in children and adolescents (trivalent inactivated influenza vaccine [TIV] and LAIV) |
B-IV |
Non-antigen components of vaccines
(other than thimerosal and ASO4 adjuvant HPV vaccine) |
B-V |
Simultaneous vaccination |
B-VI |
Safety of different products within the same vaccine category |
B-VII |
Off label use of vaccines |
B-VIII |
Vaccine-drug interactions |
31
ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs
Item |
C. Thematic Area: Special Populations
|
C-I |
Premature and low birth weight infants |
C-II |
Pregnant women |
C-III |
Adults aged ≥ 65 years |
C-IV |
Persons with primary immunodeficiency |
C-V |
Persons with secondary immunodeficiency |
C-VI |
Persons with autoimmune disorders |
C-VII |
Children with inborn errors of metabolism
|
32
ISO Agenda Draft Recommendations
#3 5-Year Priority Research Needs
Item |
D. Thematic Area: Clinical Outcomes |
D-I |
Autoimmune diseases |
D-II |
Central nervous system demyelinating disorders |
D-III |
Encephalitis/ Encephalopathy |
D-IV |
Neurodevelopmental disorders, including autism spectrum disorder (ASD) |
D-V |
Vasculitis syndromes |
D-VI |
Myopericarditis (not associated with smallpox vaccine) |
D-VII |
Clinically important outcomes related to postimmunization fever |
D-VIII |
Postvaccination syncope and sequeale |
33
CDC’s Immunization Safety Office
Scientific Agenda Presentations
Topic |
Presenter |
Slide No. |
Opening Remarks |
Dr. Iskander |
2 |
Background Information |
Dr. Broder |
3—17 |
Draft Recommendations: Overview |
Dr. Broder |
18—23 |
Draft Recommendations: 5-Year Research Needs |
Dr. Broder |
24—33 |
Considerations for Prioritization |
Dr. Snider |
34—42 |
34
Draft Recommendations
- Respond to emerging issues and conduct core, required scientific activities
- Enhance vaccine safety public health and clinical guidance capacity in 7 areas
- Address 5-Year research needs
35
1. Respond to Emerging Issues and Conduct Core, Required Scientific Activities
TASK: Provide an assessment of the relative importance (proportion of time) for each of the activity. Prioritization of activities not requested.
36
2. Enhance Vaccine Safety Public Health
and Clinical Guidance Capacity in 7 Areas
TASK: Assess relative priority of public health and clinical guidance capacity areas
37
2. Enhance Vaccine Safety Public Health
and Clinical Guidance Capacity in 7 Areas
Draft Prioritization Criteria
- Importance of strengthening this area for meeting CDC’s mandated/required vaccine safety activities?
- Importance of building capacity in this area to address the important hypotheses and thematic areas in this agenda?
- Importance of this area to advancing knowledge in vaccine safety science generally?
- Importance for CDC to take the lead in moving this area forward?
- Importance of strengthening this area to CDC’s stakeholders and the public?
- Feasibility of strengthening these areas given current resources?
38
3. Address 5-Year Research Needs
SPECIFIC Vaccine Safety QUESTIONS |
TASK: Prioritize the 5-year research needs
THEMATIC AREAS:
Vaccines and Vaccination Practices
Special Populations
Clinical Outcomes |
TASK: Prioritize the 5-year research needs
39
3. Address 5-Year Research Needs (cont.)
SPECIFIC Vaccine Safety QUESTIONS |
Draft Prioritization Criteria
- Clinical severity of the vaccine adverse event (VAE)
- Biological plausibility
- Population exposure to the vaccine
- Level of public concern
- Feasibility of designing and implementing a study
- Sufficiency of previous or ongoing research/ scientific activities
- Potential to influence clinical practice/ vaccination policy
40
3. Address 5-Year Research Needs (cont.)
THEMATIC AREAS:
Vaccines and Vaccination Practices
Special Populations
Clinical Outcomes |
Draft Prioritization Criteria
- Severity of outcome
- Population exposure to vaccine
- Biologic plausibility
- Public and scientific concern
- Sufficiency of existing knowledge
- Projected impact of the work
41
Potential Approaches for Prioritization
- Quantitative
- Interacting Group Technique
- Nominal Group Technique
- Delphi Group Technique
42
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