Investigating Adverse Events Following Vaccination

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Investigating Adverse Events Following Vaccination

• Robert C. Sparks, Research CoordinatorVanderbilt
  Vaccine Research ProgramVanderbilt University
  Medical Center1161 21st Ave. South, CCC 5319
  Medical Center NorthNashville, TN. 37232-2573

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Investigating AEFI

• Adverse Event Following Immunization
• Who? What? When? Where? Why?
• Who? Can be any patient of any age, gender, race,
  or ethnicity..patients have been as young as 2
  months old up to 70 years of age. Totally
  non-discriminatory, although some populations are
  more susceptible to AEs, such as those with
  known hypersensitivity or pre-disposing
  illness/disease
• What? Any vaccineMMR, Rotavirus, DtaP, Hep B,
  HiB, PCV, Influenza, Varicella, Hep A,
  Meningioccocal, YFany vaccine or combination
  could be a likely culprit.

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Investigating AEFI

• When? Typically the event occurs within 24 to 48
  hours following administration.but it can be
  immediate as in the case of anaphylaxis, or
  delayed longereven months after the vaccine has
  been given.
• Where? The body as a whole, or specific
  localization is possible. For example, influenza
  vaccine has been associated with Guillain-Barre
  Syndrome (GBS), (systemic), DtaP, has been linked
  with big leg syndrome (localized)
• Why? It could be hypersensitivity to specific
  components, adjuvants, preservatives, medium of
  transport, predisposition due to illness, age,
  administration error, etc. etc.

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Investigating AEFI

• Information Sources
• CISA (Clinical Immunization Safety Assessment)
• VAERS (Vaccine Adverse Event Reporting System)
• PUBLISHED ARTICLES
• SUBJECT MATTER EXPERTS
• ALLERGISTS / IMMUNOLOGISTS
• PATIENT AND / OR PARENT (often the best source)

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CISA

• Clinical Immunization Safety Assessment
• Sponsored and underwritten by CDC
• A network of principal investigators,
  coordinators, subject matter experts, associate
  fellows and others working together to
  collectively attempt to answer questions
  surrounding AEFI, such as causality,
  re-challenge, etc Located at sites around the
  country, each group has unique resources
  available, and each month, sites discuss the more
  unique AEFIs in a working group teleconference

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CISAcont.Affiliate sites

• Boston Medical Center
• Columbia University Medical Center
• Johns Hopkins University
• Northern California Kaiser Permanente
• Stanford University
• Vanderbilt University Medical Center

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CISAcont.Key Partners

• NCIRD (National Center for Immunization and
  Respiratory Diseases)
• NVAC (National Vaccine Advisory Committee)
• FDA (Food and Drug Administration)
• HRSA (Health Resources and Services
  Administration)
• ACIP (Advisory Committee on Immunization
  Practice)
• NVPO (National Vaccine Program Office)
• DoD (Department of Defense)

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VAERS

• A passive database sponsored by CDC that allows
  the investigator to enter certain criteria or
  parameters to search for cases that are similar
  in nature. This allows the group or individual to
  see if there is a trend in regards to a certain
  vaccine, group of symptoms, or an age or gender
  group. The investigator can enter groups of
  criteria including symptoms, vaccines, age
  groups, gender, U.S. reports, foreign reports,
  military reports, etc., and the database will
  search within those parameters.

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VAERS.cont.

• VAERS LINE LIST
• VACCINES PER,PPV,ROT,FLUN
• MedDRA PTs ERYTHEMA MULTIFORME
• REPORT DATE RANGE 01/01/2004 to 01/01/2009
• Primary Records Only YES
• Non-Foreign Reports Only YES
• AGE IN MOS gt 6
• Current Date MAR 03, 2009(Based on VAERS data as
  of MAR 02, 2009)

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VAERS.cont.

• A serious spontaneous report of erythema
  multiforme has been received from a physician
  concerning a three-year-old female, subsequent to
  FLUMIST. Concomitant medications included
  mometasone furoate, loratadine and montelukast
  for allergic rhinitis and congestion (patient had
  a prescription but physician was not sure if the
  patient took montelukast). On 17-Oct-2008, the
  patient received FLUMIST. She never received
  FLUMIST before. The following day on
  18-Oct-2008, the child developed a rash which
  progressed and was described as a bullseye rash
  all over body. On 19-Oct-2008, the patient was
  hospitalized for erythema multiforme. The
  patient was hospitalized for three days. The
  reporting physician did not have the patient's
  hospital records. On 24-Oct-2008, the patient
  recovered from erythema multiforme. Additional
  information received on 25-Nov-2008 was
  incorporated into the above narrative a
  diagnosis, concomitant medication, medical
  history, and demographics.Erythema multiforme A
  non-serious spontaneous report of erythema
  multiforme has been received from a Registered
  Nurse concerning a two year-old male subsequent
  to FLUMIST. This case is submitted in accordance
  with MedImmune's post-marketing commitment on
  accelerated reporting for the newly indicated
  population of 2 years to 59 months of age for
  FLUMIST. The patient received FLUMIST on
  21-Oct-2008. The patient received a total of one
  dose before onset of the event which occurred
  three days later. On 24-Oct-2008 the child was
  diagnosed with erythema multiforme. It was
  described as "raised lesions on buttocks, legs
  and abdomen." The event remains unresolved with
  the rash present.

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Published Articles

• Vaccine adverse event monitoring systems across
  the European Union
• countries Time for unifying efforts.
• Zanoni G, Berra P, Lucchi I, Ferro A, O'Flanagan
  D, Levy-Bruhl D, Salmaso S,
• Tridente G.
• Vaccine. 2009 Feb 5. Epub ahead of print
• PMID 19200851 PubMed - as supplied by
  publisher
• Acute cerebellar ataxia in the Netherlands A
  study on the association
• with vaccinations and varicella zoster infection.
• Vaccine. 2009 van der Maas NA, Bondt PE, de
  Melker H, Kemmeren JM.
• Mar 1827(13)1970-3. Epub 2009 Jan 30.
• PMID 19186201 PubMed - in process
• Factors determining utilization of a Web site by
  parents in order to report
• side effects of vaccines.
• Kimpton A, Dubé E, Sauvageau C, De Serres G.
• Can J Public Health. 2008 Nov-Dec99(6)456-9.
  French.
• PMID 19149385 PubMed - indexed for MEDLINE

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Published Articlescont.

• Safety and efficacy of a novel microneedle device
  for dose sparing
• intradermal influenza vaccination in healthy
  adults.
• Van Damme P, Oosterhuis-Kafeja F, Van der Wielen
  M, Almagor Y,
• Sharon O, Levin Y.
• Vaccine. 2009 Jan 1427(3)454-9. Epub 2008 Nov
  18.
• PMID 19022318 PubMed - indexed for MEDLINE
• Adverse events after anthrax vaccination reported
  to the Vaccine
• Adverse Event Reporting System (VAERS),
  1990-2007.
• Niu MT, Ball R, Woo EJ, Burwen DR, Knippen M,
  Braun MM VAERS
• Working Group.
• Vaccine. 2009 Jan 727(2)290-7. Epub 2008 Nov 6.
• PMID 18992783 PubMed - indexed for MEDLINE

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Subject Matter Experts, Allergists/Immunologists

• Kathryn Edwards, MD Sarah Sell Chair in
  Pediatrics, Vice Chair Pediatrics, Director
  Vanderbilt Vaccine Research Program
• Melvin Berger, MD, PhD, Senior Medical Director
  Clinical RD, CSL Behring, LLC
• Stephen C, Dreskin, MD Professor of Medicine,
  Univ of Colorado,Practice Director, Allergy and
  Immunology
• Jim Sejvar, MD, Neuroepidemiologist, CDC,
  Brighton Collaboration

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Subject Matter Experts, Allergists/Immunologists
(cont.)

• Collin Marchant, MD, Boston Medical Center
• Phil LaRussa, MD, Columbia University Medical
  Center
• Neal Halsey, MD, Johns Hopkins University
• Nicky Klein, MD, Roger Baxter, MD, Northern
  California Kaiser Permanente
• Cornelia Dekker, MD, Stanford University

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Investigating AEFI

• Many facets of investigation and information
  gathering go into critically examining an AEFI to
  determine if a causative factor can be
  determined, as well as attempting to reach a
  consensus in treatment of the event, and/or
  preventing a recurrence, particularly in cases
  where multiple doses are required to convey
  immunity. Sometimes that is not possible, as the
  information conflicts itself, such as is
  evidenced in published articles, or the risk of
  rechallenge is too great as in the case of known
  anaphylaxis.

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Investigating AEFI

• Conclusion Multiple avenues are available to
  answer the questions associated with AEFI.
  While a perfect approach to a solution is not
  always possible, the questions that do arise,
  often support more research to that end. A
  mixture of databases, published articles that
  address related issues, and a network of
  recognized leaders in the field all work in a
  collective effort to seek an answer. Each case
  must be looked at separately and the approach,
  while structured, often varies, but an open ended
  approach is key to attempting to find a causative
  factor, and addressing the question of future
  immunization.