Monitoring the safety of influenza a h1n1 2009 monovalent vaccines l.jpg
This presentation is the property of its rightful owner.
Sponsored Links
1 / 56

Monitoring the Safety of Influenza A (H1N1) 2009 Monovalent Vaccines PowerPoint PPT Presentation

Monitoring the Safety of Influenza A (H1N1) 2009 Monovalent Vaccines Claudia Vellozzi, MD, MPH Immunization Safety Office Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Atlanta, GA November 18, 2009

Related searches for Monitoring the Safety of Influenza A (H1N1) 2009 Monovalent Vaccines

Download Presentation

Monitoring the Safety of Influenza A (H1N1) 2009 Monovalent Vaccines

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Monitoring the safety of influenza a h1n1 2009 monovalent vaccines l.jpg

Monitoring the Safety of Influenza A (H1N1) 2009 Monovalent Vaccines

Claudia Vellozzi, MD, MPH

Immunization Safety Office

Division of Healthcare Quality Promotion

Centers for Disease Control and PreventionAtlanta, GA

November 18, 2009


Overall objectives for 2009 h1n1 vaccine safety monitoring l.jpg

Overall Objectives 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 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


Today s objectives l.jpg

Today’s Objectives

  • Describe the CDC’s Immunization Safety Office surveillance systems for monitoring the safety of 2009 H1N1 vaccine

  • Provide preliminary data from each of these systems


Vaccine safety datalink vsd background l.jpg

Vaccine Safety Datalink (VSD): Background

  • Established in 1990

  • A collaborative project among CDC and 8 managed care organizations (MCOs)

  • Allows for planned immunization safety studies as well as timely investigations arising from

    • hypotheses from medical literature and pre-licensure

    • reports to the Vaccine Adverse Event Reporting System (VAERS)

    • changes in immunization schedules, or the introduction of new vaccines

  • Since 2005, conducts routine Rapid Cycle Analysis (RCA) of newly licensed and approved vaccines or modifications to existing vaccine recommendations


Vsd population l.jpg

VSD Population

  • Collects medical care and vaccination data on more than 9.5 million members annually (3.1% of the US population)

  • As of 12/31/2008:

    • 2,252,024 children (<18) enrolled

      • 3.0% of US population

    • 7,245,835 adults (≥18) enrolled

      • 3.1% of US population

    • Average yearly birth cohort ~ 95,000


Vsd sites 2009 l.jpg

Group Health Cooperative

Health Partners

Marshfield Clinic

AHIP

Kaiser Permanente Colorado

So. CA Kaiser Permanente

CDC

VSD Sites: 2009

Northwest Kaiser Permanente

Harvard Pilgrim

No. CA Kaiser Permanente


Vsd data files chart review l.jpg

Hospital discharge diagnosis codes

Enrollment and demographics

+

Linked by Study IDs

Outpatient and Clinic visits

Birth and death certificate information

VSD Data Files + Chart Review

Immunizations Records


Vsd 2009 h1n1 vaccine safety monitoring specific aims l.jpg

VSD 2009 H1N1 Vaccine Safety Monitoring Specific Aims

  • Conduct rapid surveillance of 2009 H1N1 vaccine safety using

    • self controlled case series (SCCS) using binomial maximized sequential probability ratio tests (maxSPRT)

    • comparisons with historical seasonal influenza vaccines using Poisson maxSPRT

  • Conduct comprehensive analyses after immunization program is completed of associations between H1N1 vaccine and adverse events using a variety of statistical methods

    • Confirmatory Logistic Regression, SCCS, others (as needed)


Sccs example l.jpg

  • Vaccination

  • ------------------------------------------------------------------------------------------- Days -56 -15 0 42 84

  • Unexposed (pre)ExposedUnexposed (post)

  • SCCS Example


    Vsd 2009 h1n1 vaccine adverse events under surveillance l.jpg

    VSD 2009 H1N1 Vaccine Adverse Events under surveillance

    • GBS – first ever and first in a year diagnosis, complemented by chart review

    • Demyelinating disease

    • Disorders of the peripheral nervous system and neuropathies

    • Seizures (epilepsy, convulsions)

    • Encephalitis, myelitis, encephalomyelitis

    • Bell’s Palsy

    • Other cranial nerve disorders (Facial nerve disorders, Trigeminal nerve disorders)

    • Ataxia (other cerebellar ataxia, ataxia)

    • Anaphylaxis

    • Angioneurotic edema, Allergic Reaction, Urticaria

    • Myocarditis and pericarditis (LAIV only)

    • Hemorrhagic stroke (subarachnoid hemorrhage, intracerebral hemorrhage, other and unspecified intracranial hemorrhage)

    • Ischemic stroke (excludes transient ischemic attack)

    • Wheezing (LAIV only)

      • Asthma, wheezing, respiratory distress/insufficiency, other diseases of trachea/bronchi

      • Multiple definitions with and without bronchiolitis

  • Pregnancy Outcomes –

    • Spontaneous Abortions, Stillborn & Pre-eclampsia, eclampsia

  • Adjuvanted Outcomes –

    • Autoimmune hepatitis and Thrombocytopenia


  • Vsd 2009 h1n1 vaccine pregnancy studies l.jpg

    VSD 2009 H1N1 Vaccine Pregnancy Studies

    • Active surveillance in pregnant women

      • Outcomes: Fever (>100° F),allergic reactions, miscarriage, stillbirth, premature labor and preeclampsia (includes 2 VSD sites)

    • Retrospective analysis evaluating the safety of 2009 H1N1 vaccines in pregnant women and their offspring (includes all VSD sites)


    Vsd 2009 h1n1 vaccine pregnancy studies13 l.jpg

    VSD 2009 H1N1 Vaccine Pregnancy Studies

    Conduct a survey of pregnant women who receive any combination of seasonal or H1N1 vaccines or refuse vaccination (includes one VSD site)

    Specific Aims

    • Assess where and when pregnant women are vaccinated and if not vaccinated—why not

    • Accurately capture pregnancy related start dates for future linkage with the electronic medical record

    • Assess non-medically attended AEs

      • Systemic and local reactions (Fever, chills, headache, swelling, etc.)

      • ILI and URI symptoms, GI symtoms, sleep disturbances, other


    Vsd 2009 h1n1 vaccine doses administered as of nov 13 2009 l.jpg

    VSD 2009 H1N1 Vaccine Doses Administered as of Nov 13, 2009

    206,150 Inactivated Doses


    Vsd 2009 10 seasonal vaccine doses administered as of nov 13 2009 l.jpg

    VSD 2009-10 Seasonal Vaccine Doses Administered as of Nov 13, 2009


    Vsd 2009 10 seasonal influenza vaccine safety preliminary findings l.jpg

    VSD 2009-10 Seasonal Influenza Vaccine Safety Preliminary Findings


    2009 10 seasonal trivalent inactivated influenza vaccine tiv sccs preliminary results l.jpg

    2009-10 Seasonal Trivalent Inactivated Influenza Vaccine (TIV): SCCS –preliminary results

    TotalDoses Administered– 2,045,127


    2009 10 seasonal tiv historical comparison preliminary results l.jpg

    2009-10 Seasonal TIV Historical Comparison-preliminary results

    Total Doses Administered: 2,045,127


    Vsd 2009 h1n1 safety preliminary findings l.jpg

    VSD 2009 H1N1 Safety Preliminary Findings


    2009 h1n1 miv historical comparison preliminary results l.jpg

    2009 H1N1 MIV: Historical Comparison-Preliminary Results

    Total Doses Administered – 206,150


    Summary l.jpg

    Summary

    • No potential associations or signals have been identified following the monitoring of 2009-10 Seasonal TIV (2,045,127) and LAIV (100,366) doses

    • 2009 H1N1 influenza vaccines have only recently begun to be administered in the VSD MCOs and data are insufficient to assess the safety of the vaccines

    • The VSD will continue to monitor both seasonal and H1N1 influenza vaccines on a weekly basis


    Slide22 l.jpg

    EIP Guillain-Barré Syndrome (GBS) Surveillance Project:Association of Influenza A (H1N1) 2009 Vaccine and GBS


    Eip gbs surveillance sites 2009 2010 l.jpg

    New York

    Minnesota

    Oregon

    California

    Colorado

    Maryland

    Tennessee

    New Mexico

    Georgia

    Population: ~ 44.9 million

    EIP GBS Surveillance Sites, 2009-2010

    Connecticut


    Eip guillain barr surveillance gbs surveillance project l.jpg

    EIP Guillain-Barré Surveillance (GBS) Surveillance Project

    • CDC's Emerging Infections Program (EIP)

      • partnership of state and local health departments, academic centers, and CDC

      • performs surveillance and public health research on emerging infections

    • October 1, 2009 time limited surveillance for GBS

    • Objectives:

      • Rapidly detect cases of GBS and report (with vaccination status)

      • Assess and measure if there is an association between 2009 (H1N1) vaccine and GBS

    • Methods:

      • Population ~45 million persons (statewide in CT, MD, MN, NM, TN and selected regions of CA, CO, GA, NY, and OR)

      • Active network of neurologists and acute care facilities contacted weekly

      • Report all GBS cases, standardized case finding, medical record abstraction, patient interviews

      • Calculation of measures of association


    Eip guillain barre surveillance case finding l.jpg

    reported weekly

    to CDC

    10 EIP (40 million)

    Brighton

    1, 2

    Confirmed

    Clinical Network *

    Active Case-Finding

    Possible Cases

    Brighton

    3

    Probable

    Patient Interviews

    Record review;

    contact provider;

    antecedent & vaccine history

    Additional:

    Hospital discharges

    Passive provider reporting

    (reportable condition)

    AAN educational initiative;

    VAERS

    Info

    pending

    Indeterminate

    Exclusion (non-cases)

    [Brighton not met or other neurologic diagnosis]

    Re-assess

    at 14 days

    EIP Guillain-Barre Surveillance Case Finding

    * Weekly query with established network of neurology providers, sentinel pharmacies


    Descriptive epidemiology of gbs active case finding oct 1 nov 9 2009 l.jpg

    Descriptive Epidemiology of GBS Active Case Finding, Oct 1-Nov 9, 2009

    *www.Brightoncollaboration.org


    Descriptive epidemiology of gbs active case finding nov 9 2009 l.jpg

    Descriptive Epidemiology of GBS Active Case Finding, Nov 9, 2009


    Select methods using vaccine coverage data l.jpg

    Select Methods Using Vaccine Coverage Data

    • Observed vs. historical GBS rates

      • Compares observed no. GBS cases occurring within 42 days of H1N1 vaccination to expected no. among vaccinees

      • Earliest incidence metric

      • Limitations:

        • historical rate comparison (may not be valid comparison, different case finding)

        • Initially only crude, or age-specific with assumptions on vaccine administration

        • With BFRSS data, fewer assumptions needed for age-specific comparisons

    • GBS rates in vaccinated vs. unvaccinated persons

      • Use BFRSS vaccine coverage data, calculate person-time exposed and unexposed to vaccine, calculate rates

      • Strength: rates in vaccinated and unvaccinated persons will both be calculated from active surveillance data

      • Limitations

        • BRFSS data not available until mid-November and may only be available at the state level (not EIP catchment area specific)

    • GBS rates in H1N1 vaccinated vs. seasonal vaccine recipients

      • Use BFRSS vaccine coverage data

      • Age-adjust


    Real time immunization monitoring system rtims l.jpg

    Real Time Immunization Monitoring System (RTIMS)

    Contributors:

    • Johns Hopkins Bloomberg School of Public Health (JHU)

    • CDC ISO (AHIP)

    • WorldAPP (WA)

    • State and local health departments (HD)

    • Hospitals, schools, clinics, pharmacies


    Rtims l.jpg

    RTIMS

    • Automated web-based surveillance system

    • Captures self reported data from vaccine recipients

    • Predecessor: Telewatch

      • Used for monitoring patients with chronic diseases

      • Modified for monitoring yellow fever vaccine1

      • Piloted for influenza vaccine November 2008

    • Capacity:

      • On line and database: 1-10 million vaccine recipients

      • Follow-up personnel: expandable


    Objectives l.jpg

    Objectives

    To monitor influenza vaccine recipients for adverse events (early signal detection)

    To identify host factors associated with adverse events

    To compare rates of adverse events associated with different influenza vaccine products

    To expedite reporting of AEs to VAERS


    Study population l.jpg

    Study Population

    Seasonal & 2009 H1N1 Influenza vaccine recipients

    Target population – Pregnant women, health care workers, school aged children

    State & local health departments, hospitals, schools and OB clinics


    Timeline for surveys l.jpg

    Timeline for Surveys

    Baseline

    survey

    1st

    Follow up

    Pregnancy

    Follow-up?

    2nd

    Follow-up

    Day 2 Day 7 Day 42


    Study information card provided at time of vaccination l.jpg

    Study Information CardProvided at Time of Vaccination

    FrontBack


    Rtims information flow l.jpg

    RTIMS Information Flow

    Permission to Contact

    at Time of Vaccination

    or

    Electronic

    (Registries)

    or

    Vaccine

    Recipient

    Paper

    www.myflushot.org

    website sign-up

    Weblinks

    CDC, JHU, HDs

    link

    www.myflushot.org

    JHU

    Data entry

    Formatting

    WorldAPP

    RTIMS Survey

    3-4 min initial

    <1 min follow-up


    State participation active capture 31 contacted l.jpg

    State Participation - Active Capture(31 Contacted)


    4 730 baseline surveys by risk group and gender as of nov 9 2009 l.jpg

    4,730 Baseline Surveysby Risk Group and Genderas of Nov 9, 2009


    Type of vaccine received by risk group as of nov 9 2009 l.jpg

    Type of Vaccine Received by Risk Groupas of Nov 9, 2009


    Diagnoses after flu vaccine by vaccine as of nov 9 2009 l.jpg

    Diagnoses after Flu Vaccineby Vaccineas of Nov 9, 2009


    Limitations l.jpg

    Limitations

    • Surveys after vaccination

    • Possible selection bias:

      • Females more likely to participate

      • Persons with reactions more likely to complete?

      • Drop outs?

    • Some reluctance to have VAERS form filed

      • name and contact information

    • Active solicitation of symptoms

      • Some multiple symptoms


    Acknowledgements l.jpg

    Acknowledgements

    • VSD

      • Eric Weintraub

      • James Baggs

      • Frank DeStefano

    • CDC/EIP

      • Melissa Viray

      • Paige Lewis

      • Oliver Morgan

      • Scott Fridkin

    • RTIMS

      • Neal Halsey

      • Rosanna Setse


    Extra slides l.jpg

    Extra slides


    The vsd distributed data model l.jpg

    CDC

    “Direct”

    SAS Programs, Logs, Output, & Analytical Datasets

    Hub

    “Indirect”

    The VSD Distributed Data Model


    Vsd 2009 h1n1 vaccine study design and analytic plan l.jpg

    VSD 2009 H1N1 Vaccine Study Design and Analytic Plan

    • Challenges for studying the safety of influenza vaccines

      • Confounding by indication

      • Vaccine recommendations have expanded and changed

      • Influenza vaccines are often given over a very short period of time.

      • Individuals may have received vaccine outside their MCO (count as unvaccinated)

      • Seasonality of adverse events may confound interpretation

    • To address the challenges to monitor 2009 H1N1 safety more than one approach will be included in both:

      • Rapid Cycle Analyses (RCA) weekly surveillance (near real time and critical to rapid safety assessment)

      • End of season analysis


    Vsd methodological approaches in evaluating h1n1 vaccine safety l.jpg

    VSD Methodological approaches in evaluating H1N1 vaccine safety


    Vsd 2009 h1n1 vaccine adverse event definitions l.jpg

    VSD 2009 H1N1 Vaccine Adverse Event Definitions

    • Risk periods (windows)

      • AE-specific as described in published studies or biologic plausibility

      • Length of windows – vary from 2 to 60 days

      • Day of vaccination included in the risk period if it is biologically plausible for AE to occur same day of vaccination (e.g., anaphylaxis).

    • To improve the specificity

      • Limit to AEs occuring in inpatient or ED settings

      • First event to occur in a year

    • For AEs that may have more than one “new” onset in a year a shorter period of time will be included in analysis (ex;wheezing, seizures)


    How the vsd evaluates signals l.jpg

    How the VSD Evaluates Signals

    • Check data quality

    • Check inputs, background incidences, i.e. temporal trends

    • Check whether comparison groups are defined appropriately

    • Conduct the analysis using a different control group (e.g., concurrent vs. historical) or different vaccine

    • Conduct a temporal scan to see if outcomes cluster during a post-vaccination time window

    • Conduct a definitive study using logistic regression analysis

    • Review charts to confirm or exclude cases as true cases


    Weekly maxsprt results for gbs age 6 months 2007 08 season l.jpg

    Weekly maxSPRT Results for GBS, Age ≥6 Months, 2007/08 Season


    Vsd investigators and collaborators partial list l.jpg

    Centers For Disease Control, VSD team

    James Baggs, PhD

    Julianne Gee, MPH

    Natalie McCarthy, MPH

    Eric Weintraub, MPH

    Kaiser Permanente of No. California (NCK),

    Oakland CA

    Roger Baxter, MD

    Nicky Klein, MD, PhD

    Ned Lewis

    Northwest Kaiser Permanente (NWK),

    Portland OR

    Allison Naleway, PhD

    John Mullooly, PhD

    Karen Riedlinger

    Lois Drew

    Harvard Pilgrim /Harv. Vanguard (HAR)

    Boston, MA

    Tracy Lieu, MD, MPH

    Richard Platt, MD, MSc

    Katherine Yih, PhD, MPH

    Richard Fox

    Grace Lee, MD, MPH

    Sharon Greene, MD, MPH

    Group Health Cooperative (GHC), Seattle WA

    Lisa Jackson, MD, MPH

    Jennifer Nelson, PhD

    Lora Bounds

    Marshfield Clinic Rsch. Foundation (MFC)

    Marshfield WI

    Edward Belongia, MD

    James Donahue, MD

    Nick Berger

    Health Partners Rsch Foundation (HPM)

    Minneapolis MN

    Jim Nordin, MD

    Amy Butani

    Kaiser Permanente of Colorado (KPC)

    Denver, CO

    Simon Hambidge, MD, PhD

    Jason Glanz, MS, PhD

    David McClure, PhD

    Matt Daley, MD

    David Ryerson

    So. California Kaiser Permanente (SCK), CA

    Los Angeles, CA

    Steven Jacobson, MD, PhD

    Wansu Chen, MS

    Sungching Glenn, MS

    VSD Investigators and Collaborators - Partial List

    Sites include > 125 staff working on VSD


    Eip guillain barre surveillance timeline l.jpg

    Case Only Methods:

    Descriptive Epidemiology

    Observed vs. Background Rates of GBS:

    Crude and Age-Specific Comparisons

    Estimated GBS Rates in Vaccinated vs. Unvaccinated Persons:

    Crude and Age-Specific Comparisons

    Case-Cohort analysis

    BRFSS Vaccine Coverage Data Available

    Potential Analytic Studies:

    Self Control Case Series (SCCS)

    NOV

    DEC

    JAN

    FEB

    MAR

    APR

    MAY

    OCT

    EIP Guillain-Barre Surveillance Timeline

    Vaccine Delivered


    4 790 completed baseline surveys by risk group and age group as of nov 9 2009 l.jpg

    4,790 Completed Baseline Surveysby Risk Group and Age Groupas of Nov 9, 2009


    Diagnoses after flu vaccine by gender as of nov 9 2009 l.jpg

    Diagnoses after Flu Vaccineby Genderas of Nov 9, 2009


    Daily visits to http www myflushot org l.jpg

    Daily Visits to http://www.myflushot.org


    Links clicked on to arrive at http www myflushot org l.jpg

    Links clicked on to arrive at http://www.myflushot.org

    HITSEntry Link________________________________________________________

    3615http://www.cdc.gov/h1n1flu/vaccination/public/vaccination_qa_pub.htm

    3486Unknown

    1240http:// www.cdc.gov/h1n1flu/vaccination/vaccine_safety_qa.htm

    1123Entered URL directly

    917http:// www.cdc.gov/h1n1flu/vaccination/

    589http:// www.cdc.gov/h1n1flu/vaccination/vaccine_keyfacts.htm

    564http:// www.cdc.gov/H1N1flu/vaccination/pregnant_qa.htm

    358http:// www.cdc.gov/h1n1flu/vaccination/gbs_qa.htm

    327http:// www.cdc.gov/h1n1flu/vaccination/vaccine_safety.htm

    303http:// www.in.gov/flu/

    178http:// www.cdc.gov/h1n1flu/vaccination/general.htm

    105http:// cdc.gov/h1n1flu/vaccination/public/vaccination_qa_pub.htm

    103http:// www.in.gov/flu/2443.htm

    94 http:// www.vaccinesafety.edu/

    >60% of traffic comes from the CDC


    2009 10 seasonal tiv historical comparison preliminary results56 l.jpg

    2009-10 Seasonal TIV Historical Comparison-preliminary results

    Total Doses Administered: 2,045,127


  • Login