Presentation on theme: "Vaccine Safety Surveillance"— Presentation transcript:
1Vaccine Safety Surveillance Experiences and Lessons LearnedSupporting the Military Health System (MHS)Mandatory Immunization ProgramsSMMAC: Scientific Military Medical Advisory CommitteeCOL Renata J. M. Engler, MDDirector, Vaccine Healthcare Centers Network2007 Updates
3Challenges: Current & Future Vaccine Safety Surveillance Biodefense: from preventive health to terrorism & pandemic preparedness – immune modulatorsMandatory active or passive vaccine programsService members AD/Reserve: 2,400,000DoD employees > 2,000,000Beneficiaries > 6,000,000Homeland defense support Millions++Adverse vaccine side effects/reactions managementSerious AE, exemption management? 1-2%Individual causality assessments new skills requiredFor service members alone ,000Multiple vaccines, drugs + vaccines clinical questionsImplications for disability clarification ?Complex case evaluation, documentation, causality?
4Department of Defense Largest Adult Immunization Program Most complex immunization exposuresUsual recommended ACIP vaccines: ever expanding in numberTravel vaccines mixed in new ways: safety data?Biodefense vaccines: anthrax and smallpox with potential expansionMandatory employment requirementMedical and administrative exemption processDemand for clinical competencies that represent “new specialty”Complex new questions for which there is no literature, guidelinesWhen to exempt and when notHow to optimize care of adverse events guidelinesNeed for clinical research to validate “opinion” guidelinesUnique challenges in delivery system: ongoing trainingTraditional and non-traditional sites with personnel turnover, globalWorking towards NVAC minimum standards MMWR Mar 2000
5DoD Requirements Immunizations As “Operational Drugs” More Vaccines – increasing safety and efficacy concerns Immunization complexity, standards, clinical ?’s Trust in vaccines: risk communication complexityAnthrax Vaccine Immunization Program AVIPComplex clinical problems arise – how best to assessEpidemiological safety versus individual responsesSmallpox vaccination programIncrease in clinical needs & educational support requirement for clinical expertise & consultationIdentify & manage adverse reactions over timeNew case definitions: critical to future genetic researchVHC Network = Response to Clinical ConcernsStart Working to Address the Unanswered Questions, Diversity
6DoD Vaccine Program Policy Vaccine Healthcare Centers (VHC) Network Science – Quality – Confidence – CarePolicyMilitary Vaccine Program (MILVAX)Vaccine Healthcare Centers (VHC) NetworkPolicy & Clinical Practice ImprovementsClinical Consultations, Investigations, Advocacy, VAERS SupportClinicalCentralized locationPolicyProgram administrationProgram logisticsRegional sites w/dense Active DutyVaccine safety surveillance/researchPatient/provider advocateClinical consultant, registry support
7DoD Service Members Beneficiaries and Employees Receiving mandatory vaccines as part of employmentEligibility for National Vaccine Injury Compensation ProgramIF, vaccine is part of childhood mandatory vaccine scheduleInformation about this program included in new Joint RegulationsSupport needs: preparation of comprehensive clinical summaries needed for VICP applications if requested? What are competencies?Challenges for such evaluationsHow to sort out question of multiple vaccines: usual in DoDEXAMPLE of New Clinical Immunology Concerns: vaccinia is a powerful TH1 immune adjuvant – what are the dangers of early diphtheria-tetanus immunization with pertussis in the context of vaccinia adjuvant effects? Should they be mixed?Recognition of possible rare adverse eventsExample: thrombocytopenia after MMR – does it occur in adults?
8MILVAX with Regional Analysts VHC Network with Regional Sites Global Outreach Logistic & Clinical ServicesDevelop the needed infrastructure for global support of mandatory vaccine programs: education, consultation, availability, problem solvingNew program launch and implementation of policyMulti-site rare adverse events surveillance & definitions assistanceSupports future clinical vaccine safety research; phenotype genotypeVAERS education, program quality improvementFacilitate needed health care worker culture changesStandards for minimum quality: outreach educationRegional lines of referral for complex VAERSMultidisciplinary case management and education support services coordination, feedback to front lines for care quality improvements, practice variancesFacilitate mass immunization programs as neededRapid feedback infrastructure on lessons learned, issues in need of resolution, dissemination of changesEvolving clinical guidelines rapidly based on lessons learned
9Challenges in Vaccines Military Allergy-Immunology Restart of mandatory anthrax vaccine immunizationsLimited to those deploying to high threat areasPackage insert 2002 version – awaiting reanalysis of data regarding dose reduction route change study example of evolving data post marketing-licensure: “knowledge changing as science evolves”Pregnancy and anthrax vaccine exposure question in MILVAX trifoldSystemic prolonged side effects/adverse events still being definedLong term complications of large local reactions: neuropathyAdditional data regarding gender differencesNot just for local but also systemic reactionsHow do we best support high responder-low responder differencesNew VaccinesTdap for adults: caution with high responders, neurologic AEs?Human papilloma virus vaccine: new mixtures
10Educational Products at www.anthrax.mil TrifoldWHAT YOU NEED TO KNOW ABOUT ANTHRAX VACCINE1. Powerpoint Briefing Slides2. Watch On-line Multi-Media Briefings3. Questions and Answers4. Service Messages2007> 1.5 millionVaccinated> 5.9 millionDosesVHC: Ongoing Commitment toLife-Cycle Vaccine Safety SurveillanceEvolving Case Definitions for More Severe Side EffectsFor more information:877-GET-VACC,DSN
11Vaccinia Safety Enhancement With Increased Surveillance Triservice/DODExpert ConsensusClinical GuidelinesFor Post Vaccinia MyopericarditisCoordinated by VHC Network Based OnIn-Depth Case Investigations & Causality AssessmentsAccess for complete tables plus algorithm documentsIterative Updates With Case Reviews2007 Revision underway1.1 million vaccineesScreening standardized- Eczema vaccinatum risk, etc.Outcomes of programSignificant reduction in historically predicted serious adverse eventsProgressive vaccinia:Eczema vaccinatum:(10-15/million historically)“New-Old” MyopericarditisAnticipated in pre-launch training program, added chest pain to diaryCentralized case managementRegistry process evolved for longer clinical follow-up and support-consultation servicesQuality improvement to VAERS
12Smallpox Vaccine Myopericardits & Beyond > 1.1 million vaccinatedMyopericardits risk at ~1:6-7K but actual risk may be higherRecurrence spontaneously: cases under investigationDeaths: 2 “possible” associations both with evidence of eosinophilic myopericarditis on autopsyEvolving clinical guidelines for diagnosis and treatment based on ongoing review of case based clinical experienceOther new adverse events case definitions in progressExample: new onset acute urticaria, angioedema evolving to chronic disease after live virus vaccinesLabor intensive, slow process of in depth causality assessments withOutcomes follow upAssistance with diagnosis and treatmentIterative case review to refine case definitions (WHO criteria)
13http:// www.smallpox.mil http:// www.vaccines.mil DoD Smallpox Website –
14To order, email firstname.lastname@example.org 2nd edition, 2004 Immunization Tool Kit Learning Management System (LMS):SupportingImmunization UniversityMeeting RequirementsCompetency &Quality STDsNew Joint RegulationsTo order,2nd edition, 20043rd edition 20054th edition 2006 pendingPDA & PDF available on websiteAnnual Updates2007 Edition PendingRequests for Biodefense Modules
16Quality ImprovementEducational outreach to enhance understanding of vaccine adverse events reporting system submissionsImmunization University with emphasis on VAERSTraining materials distributed at time of immunizationSupport services to complete VAERS with causality assessmentsOngoing challengesMedical school and residency training limited beyond vaccine schedulesDuring outreach training, misconceptions and reasons for reporting frequently confused by providers and healthcare workersAwareness of Vaccine Injury Compensation ProgramLimited among most health care workers and vaccineesCausality assessments and documentation critical to process
17Defense Medical Surveillance System (DMSS) Highlighted by IOM as a valuable resourceHospitalizations and outpatient visit diagnostic codes since ~2000Earlier years: coding quality and use of system variableImmunization registryComprehensive for anthrax and smallpox vaccines, then influenzaIn future: anticipated improvements in comprehensive vaccine recording for all servicesAir Force more comprehensive since 2000Resource for epidemiological studiesLimited ability to validate diagnostic codesMethodologies with healthy warrior effects raise questionsGender, ethnic differences have not been adequately considered in past analyses and require further considerationDoes the MHS need a VSD equivalent?Improve safety surveillance for new complex vaccine mixtures
18Vaccine Safety Questions DoD Clinical Vaccine Call Center ASKVHC Written Inquires, Case Reviews Headaches, new onset, reproducibleMuscle and joint pains that persistAutoimmune hepatitisRisk factors?Multiple vaccinesGenetic riskGenderEthnicityAtopyOthersRelative/Absolute ContraindicationsManagement strategies?Side Effects/Adverse EventsStrategies for treatment & prophylaxisRare Adverse Events QuestionsHair loss & hepatitis B/vaccinesBleeding disorderDiabetesChronic fatigue syndromeNeuropathyArthritisAutoimmunityType 1 adult onset diabetesChest pain after influenzaPemphigus & vaccinesImmediate hypersensitivityThrombocytopeniaClinicians as well as patients seeking clinical not epidemiological information with frequently complex scenarios.Challenge: rapidly evolving clinical guidelines, evidence to validate the guidelines.
19Secure Consultative E-mail VHC Network Goals “Caring for Those Who Serve: Before & After Immunizations”Vaccine Clinical Support & Consultation ServicesAdverse events & efficacy case management, medical exemptionsVaccine SafetySurveillance, reporting & adverse events registry, long term follow-upImmunization EducationFor Health Care Workers & Service Members, Beneficiaries, DoD, etc.Integrate with Immunization UniversitySupport for ResearchClinical focus, post-licensure, to “enhances vaccine safety, efficacy & acceptability”Adult military vaccine related gapsAdvocacyFor quality immunization healthcare deliveryFor care of complex AE’sNetwork of MTF-linked SitesNOT service specific but regionalOutreach & Support 24/7Clinical Call CenterSecure Consultative
20MILVAX MissionWhat have you done for them today?
21Research Commitments (Partial List) Built on VHC Network Platform Protocols*Partial ListingCollaboratorsWRAMC/NARMC+FundingExtramuralSmallpox Vaccine Myopericarditis Immunogenetics*CDC-CISA/KaiserU of Washington Molecular ImmunologyCDC-CISANIAID/NIHAnthrax Vaccine Adverse Events - Immunogenetics*U of Oklahoma Rheum-ImmunologyAnthrax Vaccine & Pemphigus Antibodies*U of Pennsylvania ImmunodermatologyAnthrax Vaccine Side Effects Tripler Data Review*MRMC/Ft DetrickMRMCHalf Dose Flu Vaccine Study*(To be finalized this year)CDC/Civ Academic/ NIAID/ USAMMDAAMEDD/CDC/ NIAID/USAMMDAVaccine TelemedicineTechnology Development*VHC-Allergy-Immunol Department, WRAMCP8 Grants, MRMCVAERS KAB Survey*VHC-CDCCDC-NIPExercise Exacerbated Prolonged Myalgia/Arthralgia/FatigueVHC-Georgetown-U of MD Collaborative Grant ApplicExtramural to USAMRIID May 2007*IRB/HUC Approved
22End of BriefingThe views expressed in this presentation are those of the author and do not reflect the official policy of the Department of Army, Department of Defense, or US Government. Questions?
23References Based on VHC Network Enhanced VAERS Arness MK, Eckart RE, Love SS, Atwood JE, Wells TS, Engler RJ, Collins LC, Ludwig SL, Riddle JR, Grabenstein JD, Tornberg DN. Myopericarditis following smallpox vaccination. Am J Epidemiol Oct 1;160(7):Wollenberg A, Engler R. Smallpox, vaccination and adverse reactions to smallpox vaccine. Curr Opin Allergy Clin Immunol Aug;4(4): Review.Eckart RE, Love SS, Atwood JE, Arness MK, Cassimatis DC, Campbell CL, Boyd SY, Murphy JG, Swerdlow DL, Collins LC, Riddle JR, Tornberg DN, Grabenstein JD, Engler RJ; Department of Defense Smallpox Vaccination Clinical Evaluation Team. Incidence and follow-up of inflammatory cardiac complications after smallpox vaccination. J Am Coll Cardiol Jul 7;44(1): Review.Cassimatis DC, Atwood JE, Engler RM, Linz PE, Grabenstein JD, Vernalis MN. Smallpox vaccination and myopericarditis: a clinical review. J Am Coll Cardiol May 5;43(9): Review.NOTE: Myopericarditis is an autoimmune phenomenon with an undefined future risk from revaccination or other environmental exposures; unanswered research questions require LONG TERM follow up – ongoing challenge to manage organizational barriers