Document text
Development of the U.S. Childhood Vaccine Schedule
Aaron SiriACIP Meeting, December 5, 2025With A Focus on Suggested Improvements
DisclosuresManaging Partner of Siri & Glimstad LLP with 100+ professionals who handle civil rights, exemptions, immigration, employment, and injury claims related to vaccination. Author of Vaccines, Amen: The Religion of Vaccines.
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Growth of U.S. Childhood Vaccine Schedule
Growth of U.S. Vaccine Schedule
4Source:https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html
1983 U.S. Vaccine Schedule
Growth of U.S. Vaccine Schedule2025 U.S. Vaccine Schedule
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Source: https://www.cdc.gov/vaccines/hcp/imz-schedules/downloads/child/0-18yrs-child-combined-schedule.pdf
Growth of U.S. Vaccine Schedule1983 v. 2025 U.S. Childhood Vaccine Schedule
6Reflects: stand-alone routine vaccines given at earliest recommended age; and 3-dose RV, 4-dose Hib, and 2-dose HPV series. Sources: https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html; https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html; https://www.cdc.gov/vaccines-pregnancy/hcp/vaccination-guidelines/index.html Routine Vaccines: In Utero to 18 Years
Vaccines given<12 months of ageVaccines given > 12 months of age19832025DTP (2 Months)OPV (2 Months)DTP (4 Months)OPV (4 Months)DTP (6 Months)MMR (15 Months)DTP (18 Months)OPV (18 Months)DTP (4 Years)OPV (4 Years)Td (14 Years)IPV (6 Months)Hep B (6 Months)Flu (6 Months)Flu (7 Months)Hib (12 Months)PCV (12 Months)Hep A (12 Months)VAR (12 Months)MMR (12 Months)DTaP (15 Months)Hep A (18 Months)Flu (2 Years)Flu (3 YearsDTaP (4 Years)IPV (4 Years)Flu (4 Years)MMR (4 Years)VAR (4 Years)Flu (5 Years)Flu (6 Years)Flu (7 Years)Flu (8 Years)Flu (9 Years)Flu (10 Years)Tdap (11 Years)HPV (11 Years)Flu (11 Years)HPV (11 Years)MenACWY (11 Years)Flu (12 Years)Flu (13 Years)Flu (14 Years)Flu (15 Years)MenACWY (16 Years)Flu (16 Years)Flu (17 Years)Flu (18 Years)TdaP (In Utero)Flu (In Utero)RSV (In Utero or Birth)Hep B (Birth)Hep B (1 Month)RV (2 Months)DTap (2 Months)Hib (2 Months)PCV15 (2 Months)IPV (2 Months)RV (4 Months)DTap (4 Months)Hib (4 Months)IPV (4 Months)PCV15 (4 Months)RV (6 Months)DTap (6 Months)Hib (6 Months)PCV15 (6 Months)
Growth of U.S. Vaccine Schedule1983 v. 2025 U.S. Childhood Vaccine Schedule
7Routine + Shared Decision-Making Vaccines (Covid-19 and MenB)
Reflects: stand-alone routine vaccines given at earliest recommended age; and 3-dose RV, 4-dose Hib, 2-dose HPV, and 3-dose Covid-19 series. Sources: https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html; https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html; https://www.cdc.gov/vaccines-pregnancy/hcp/vaccination-guidelines/index.html Vaccines given<12 months of ageVaccines given > 12 months of age19832025DTP (2 Months)OPV (2 Months)DTP (4 Months)OPV (4 Months)DTP (6 Months)MMR (15 Months)DTP (18 Months)OPV (18 Months)DTP (4 Years)OPV (4 Years)Td (14 Years)Covid-19 (11 Years)Flu (12 Years)Covid-19 (12 Years)Flu (13 Years)Covid-19 (13 Years)Flu (14 Years)Covid-19 (14 Years)Flu (15 Years)Covid-19 (15 Years)MenB (16 Years pt.1)MenACWY (16 Years)Flu (16 Years)MenB (16 Years pt.2)Covid-19 (16 Years)Flu (17 Years)Covid-19 (17 Years)Flu (18 Years)Covid-19 (18 Years)TdaP (In Utero)Flu (In Utero)RSV (In Utero or Birth)Hep B (Birth)Hep B (1 Month)RV (2 Months)DTap (2 Months)Hib (2 Months)PCV15 (2 Months)IPV (2 Months)RV (4 Months)DTap (4 Months)Hib (4 Months)IPV (4 Months)PCV15 (4 Months)RV (6 Months)DTap (6 Months)Hib (6 Months)PCV15 (6 Months)IPV (6 Months)Hep B (6 Months)Flu (6 Months)Covid-19 (6 Months)Flu (7 Months)Covid-19 (7 Months)Covid-19 (9 Months)Hib (12 Months)PCV (12 Months)Hep A (12 Months)VAR (12 Months)MMR (12 Months)DTaP (15 Months)Hep A (18 Months)Flu (2 Years)Covid-19 (2 Years)Flu (3 YearsCovid-19 (3 Years)DTaP (4 Years)IPV (4 Years)Flu (4 Years)MMR (4 Years)VAR (4 Years)Covid-19 (4Years)Flu (5 Years)Covid-19 (5 Years)Flu (6 Years)Covid-19 (6 Years)Flu (7 Years)Covid-19 (7 Years)Flu (8 Years)Covid-19 (8 Years)Flu (9 Years)Covid-19 (9Years)Flu (10 Years)Covid-19 (10 Years)Tdap (11 Years)HPV (11 Years)Flu (11 Years)HPV (11 Years)MenACWY (11 Years)
Growth of U.S. Vaccine Schedule
1983 v. 2025 U.S. Vaccine Schedules
8Routine Vaccines: In Utero To 12 Months
Reflects stand-alone routine vaccines given at earliest recommended age; and 3-dose RV and 4-dose Hib series. Sources:https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html; https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html; https://www.cdc.gov/vaccines-pregnancy/hcp/vaccination-guidelines/index.html
Growth of U.S. Vaccine Schedule2025 U.S. Vaccine Schedule
9All data reflects rates at approximately 2 years of age except for Tdap, HPV, and MenACWY which reflect the rate for ages 13 to 17. Sources: https://web.archive.org/web/20190618125412https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/coverage-levels.pdf; 1983 IIV uptake is an estimate; https://www.cdc.gov/mmwr/volumes/73/wr/mm7338a3.htm; https://www.cdc.gov/mmwr/volumes/70/wr/mm7035a1.htm?s_cid=mm7035a1_wRoutine Vaccine Coverage: United States 1983 v. 20201983202066%65%57%3%0%0%0%0%0%0%0%0%MMRDTPOPVIIVHepBHibPCVRVVARHepATdapHPV0%MenACWY3+ Doses1+ Doses3+ Doses94%92%93%63%93%94%
DTaPMMRIPVIIVHepBHibPCVRVVARHepATdapHPVMenACWY1+ Doses3+ Doses3+ Doses2+ Doses3+ Doses2+ Doses93%3+ Doses77%2+ Doses91%1+ Doses88%1+ Doses90%1+ Doses75%1+ Doses89%1+ Doses
Pre-Licensure Safety: U.S. Childhood Vaccine Schedule
Pre-Licensure Safety of the U.S. Vaccine ScheduleImportance of Clinical Trials
11* Stand-alone vaccines for children, excluding influenza; IPOL date is an estimate; DTP date uncertain. Source of data: see accompanying memorandum.Vaccine*Year Licensed for ChildrenYear ACIP Recommended for Routine Use in Children [Earlier Non-Routine Use]Days Between Licensure & RecommendationDTP (various)M-M-R-II (Merck)MenomuneRecombivax HB (Merck)Engerix-B (GSK)PedvaxHIB (Merck)Ipol (Sanofi)ActHIB (Sanofi)Varivax (Merck)Havrix (GSK)Vaqta (Merck)Infanrix (GSK)Prevnar 7*19781981198619891989199019931995199519961997200019661978199119911990 199719931996 2006 200619972000*49 days 1948 days 816 days133 days 2580 days24 days294 days 4104 days 3703 days73 days-1 days[1985][1987][1990][1994][1996][1996][1264][331][192][1691][674][273]Vaccine*Year Licensed for ChildrenYear ACIP Recommended for Routine Use in Children [Earlier Non-Routine Use]Days Between Licensure & RecommendationDaptacel (Sanofi)Boostrix (GSK)Adacel (Sanofi)Menactra (Sanofi)Gardasil (Merck)Hiberix (GSK)Prevnar 13 (Pfizer)Menveo (GSK)Gardasil-9MenQuadfi (Sanofi)Vaxneuvance (Merck)Priorix (GSK)Prevnar 20 (Pfizer)2002200520052005200620092010201020142020202220222023200220052005200520062009201020102015202020222022202352 days24 days20 days27 days21 days30 days0 days19 days78 days62 days5 days17 days56 daysCurrent routine vaccine recommended for children.Previously recommended for children and used as control to license currently recommended vaccine.
Pre-Licensure Safety of the U.S. Vaccine ScheduleQuality of Trials Crucial
12Source: * https://www.fda.gov/media/130326/download † https://jamanetwork.com/journals/jamapediatrics/fullarticle/2714387 ControlSafety Review PeriodPowerA placebo (defined by FDA as “inert substances”*) or another vaccine for same indication that was properly trialed prior to licensure.To “provide complete safety data across all critical periods of growth and development,” as compared to trials for adults, “data on drug efficacy and safety in children may require an additional 6 years.” JAMA Pediatrics, author affiliations Office of Pediatric Therapeutics, FDA, and Duke Clinical Research Institute.†Enough participants to assess if benefits outweigh risks.Critical to avoid bias.Randomized and Blinded
Pre-Licensure Safety of the U.S. Vaccine ScheduleDrug Trials
13Trials Relied Upon to License Pfizer’s Top 4 Most Profitable Drugs*
* As of 2019. Sources: https://moneyinc.com/the-five-highest-selling-pfizer-drugs-of-all-time/; https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases Eliquis 7.4 Years PlaceboLipitor4.9 YearsPlaceboLyrica2 YearsPlaceboDRUG SAFETY REVIEW CONTROL Enbrel 6.6 Years Placebo
Pre-Licensure Safety of the U.S. Vaccine ScheduleChildhood Vaccine Trials
“[W]idespread vaccine hesitancy observed during the Covid-19 pandemic suggests that the public is no longer satisfied with the traditional safety goal of simply detecting and quantifying the associated risks after a vaccine has been authorized for use.”“Postauthorization studies are needed to fully characterize the safety profile of a new vaccine, since prelicensure clinical trials have limited sample sizes, follow-up durations, and population heterogeneity.”14
Source: https://www.nejm.org/doi/full/10.1056/NEJMp2402379
Pre-Licensure Safety of the U.S. Vaccine ScheduleControls Routine Vaccines: Birth to 6 Months
15Lists stand-alone routine vaccines. Some DTP trials use other DTP vaccines as a control but none licensed based on placebo-controlled trial. See supporting memorandum for sources.Vaccine TypeVaccineControlPlacebo?Hep BEngerix-B (GSK)No controlRecombivax HB (Merck)No controlDTaPInfanrix (GSK)DTP No controlDaptacel (Sanofi)DTP No controlHibActHIB (Sanofi)Hep B No controlHiberix (GSK)ActHIB Hep B No ControlPedvaxHIB (Merck)Lyophilized PedvaxHIB Injection of lactose, aluminum adjuvant, and thimerosalPCVVaxneuvance (Merck)Prevnar 13 Prevnar 7 Investigational vaccinePrevnar 20 (Pfizer)Prevnar 13 Prevnar 7 Investigational vaccineIPVIpol (Sanofi)No controlIIVVariousNo placebo control – see memorandumNONONONONONONONONONONO
Pre-Licensure Safety of the U.S. Vaccine ScheduleControls Routine Vaccines: 7+ Months of Age
16Lists stand-alone routine vaccines. See supporting memorandum for sources.Vaccine TypeVaccineControlPlacebo?MMRM-M-R-II (Merck)No controlPriorix (GSK)M-M-R-II No controlVaricellaxVarivax (Merck)Injection of 45mg of neomycin per ml (465 subjects)Havrix (GSK)Engerix-B No controlHep AVaqta (Merck)Injection of AAHS and thimerosalBoostrix (GSK)Decavac No controlAdacel (Sanofi)Decavac No controlTdapGardisil-9 (Merck)Gardasil or Placebo+Gardasil (3 doses) (306 subjects)HPVMenveo (GSK)Menactra Menomune No controlMenACWYMenQuadfi (Sanofi)Menveo Menactra Menomune or Menactra No controlNONONONONONONONONONOInjection of AAHS or Gardasil carriersolution (yeast protein...) (320 subjects)
Pre-Licensure Safety of the U.S. Vaccine ScheduleSafety DurationsSafety in childhood trials is typically reviewed for 6 months or less after injection—often only days or weeks.
17Stand-alone routine infant vaccines. See supporting memorandum for sources.Vaccine TypeVaccineSolicited ReactionsUnsolicited ReactionsHep BRecombivax HB (Merck)5 daysEngerix-B (GSK)4 daysHibActHIB (Sanofi)3 daysPedvaxHIB (Merck)3 daysDTaPHiberix (GSK)4 daysInfanrix (GSK)8 daysDaptacel (Sanofi)14 daysIPVIPOL (Sanofi)3 daysVaxneuvance (Merck)14 daysPrevnar 20 (Pfizer)7 daysDuration of Safety Review After Injection
PCV5 days4 days30 days3 days31 days30 days6 months3 days6 months6 months
Pre-Licensure Safety of the U.S. Vaccine ScheduleStatistical PowerInsufficient number of children in trials to assess if benefits outweigh risks.
18See supporting memorandum for discussion and sources.
Example: First vaccine on the schedule, Hep B
Pre-Licensure Safety of the U.S. Vaccine ScheduleExample: Hep B Vaccines
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Sources: https://www.fda.gov/vaccines-blood-biologics/vaccines/recombivax-hb; https://www.fda.gov/vaccines-blood-biologics/vaccines/engerix-b
Pre-Licensure Safety of the U.S. Vaccine ScheduleExample: Hep B Vaccines
20Source: https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm
295281229438142528292Cited Articles Involving Children Receiving Recombivax, Engerix-B, or Other Recombinant DNA VaccinePMIDSafety Monitoring After InjectionNumber of ChildrenFunding7 days5 days3 days122794,250Merck conducted and fundedIMerck conducted and fundedGSK funded
Pre-Licensure Safety of the U.S. Vaccine ScheduleExample: Hep B Vaccines
21Source: https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/02-langer-hep-b-508.pdf; https://www.nationalacademies.org/read/13164/chapter/2#2
ACIP Presentation:September 18, 2025Institute of Medicine FindingsAdverse Event – Hep B VaccineAnaphylaxisEncephalitisEncephalopathySeizuresAcute Disseminated EncephalomyelitisTransverse MyelitisOptic NeuritisNeuromyelitis OpticaMultiple Sclerosis OnsetMultiple Sclerosis RelapseFirst Demyelinating EventGuillain-Barre SyndromeCIDPSupportsInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateBrachial NeuritisErythema NodosumSystemic Lupus ErythematosusVasculitisPolyarteritis NodosaPsoriatic ArthritisReactive ArthritisInadequateRheumatoid ArthiritisJuvenile Idiopathic ArthiritisType 1 DiabetesFibromyalgiaInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateAdverse Event – Hep B VaccineThe Evidence on Causation:Supports, Rejects, or InadequateThe Evidence on Causation:Supports, Rejects, or Inadequate
Pre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV VaccinesFirst Licensed PCV Vaccine: PCV-7Licensed: February 17, 2000Control: “Investigational meningococcal group C conjugate vaccine”Safety review: 30 days (emergency room), 60 days (hospitalizations), longer (select conditions)
22Source: https://stacks.cdc.gov/view/cdc/76558; https://jamanetwork.com/journals/jama/fullarticle/199581
“Prior to licensure … the control group in the main study received another experimental vaccine, rather than a placebo. If both vaccines provoked similar adverse effects, little or no difference between the 2 groups might have been evident.” Also noting the “limited sample sizes of trials.”
__________________________________________________________________________________________ACIP Added to Schedule: February 16, 2000
Pre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV VaccinesSecond Licensed PCV Vaccine: PCV-13
23Source: https://www.fda.gov/media/107657/download; https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5911a1.htm; https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event
•Death•Life-threatening•Hospitalization•Disability or Permanent Damage•Congenital Anomaly/Birth Defect•Required Intervention to Prevent Permanent Impairment•Require Medical or Surgical Intervention to Prevent an Outcome Above
Licensed: February 24, 2010ACIP Added to Schedule: February 24, 2010
Pre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV VaccinesThird Licensed PCV Vaccine: PCV-15Licensed: June 17, 2022ACIP Added to Schedule: June 22, 2022
24Source: https://www.fda.gov/media/150819/download
Pre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV Vaccines Recap
25Days in each box reflects period between licensure & ACIP addition to scheduleInvestigationalVaccinePrevnar 7-1 DAYSPrevnar 130 DAYSVaxneuvance5 DAYSPrevnar 2056 DAYS
Pre-Licensure Safety of the U.S. Vaccine ScheduleFinal Example: DTaP Vaccines2014 SAGE Systematic Review“The majority of studies indicated a deleterious effect of DTP on mortality.”26Source: https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Apr2014/9_session_non-specific_vaccine_effects/Apr2014_session9_epidemiologic_review.pdfDays in each box reflects period between licensure & ACIP addition to scheduleDTPInfanrixDaptacel73 DAYS52 DAYS
Pre-Licensure Safety of the U.S. Vaccine ScheduleFinal Example: DTaP Vaccines
27Source: https://pubmed.ncbi.nlm.nih.gov/28188123/. See memorandum for discussion and additional sources.
Pre-Licensure Safety of the U.S. Vaccine ScheduleNon-Routine VaccinesExample: Dengue VaccineClinical Trial:•Safety Review: 6 Years for severe dengue•Control: Placebo•Size: 30,000+Findings:•Age <6: increased risk of severe harm and death from the vaccine•Age >6 and never had dengue: increased risk of severe harm and death from the vaccine28Source: https://www.fda.gov/media/125481/download; https://www.fda.gov/media/124379/download
Pre-Licensure Safety of the U.S. Vaccine ScheduleDrug Trials v. Vaccine Trials
29Trials Relied Upon to License Pfizer’s Top 4 Most Profitable Drugs*
* As of 2019. Sources: https://moneyinc.com/the-five-highest-selling-pfizer-drugs-of-all-time/; https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-statesEliquis 7.4 Years PlaceboLipitor4.9 YearsPlaceboLyrica2 YearsPlaceboDRUG SAFETY REVIEW CONTROL Enbrel 6.6 Years Placebo
Pre-Licensure Safety of the U.S. Vaccine ScheduleImpact of Immunity on Market Forces
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See supporting memorandum
Pre-Licensure Safety of the U.S. Vaccine ScheduleEthics Of Relying On Improperly Controlled Trials
31Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC1113953/“In some trials placebos were omitted on ethical grounds. This is illogical because studies destined to produce unreliable results should themselves be considered unethical.”British Medical JournalAuthor affiliations: University of Oxford, Oxford Radcliffe Hospital, Radcliffe Infirmary, and Geneva University Hospital
Pre-Licensure Safety of the U.S. Vaccine ScheduleRevisit ACIP Recommendations
32Robust clinical trial data should support the safety of each recommendation.
Post-Licensure Safety: U.S. Childhood Vaccine Schedule
Post-Licensure Safety of the U.S. Vaccine Schedule1991 IOM report: Adverse Effects of Pertussis and Rubella Vaccines
Source: https://www.nationalacademies.org/publications/181534Vaccine TypePertussis1. Acute encephalopathy 2. Shock and “unusual shock-like state” 3. Anaphylaxis 4. Protracted, inconsolable crying1. Autism 2. Aseptic meningitis 3. Chronic neurologic damage 4. Erythema multiforme or other rash 5. Guillain-Barre syndrome 6. Hemolytic anemia 7. Juvenile diabetes 8. Learning disabilities and attention-deficit disorder 9. Peripheral mononeuropathy 10. Thrombocytopenia 11. Radiculoneuritis and other neuropathies 12. Thrombocytopenic purpuraRubella5. Chronic arthritis 6. Acute arthritis1. Infantile spasms 2. Hypsarrythmia 3. Reye syndrome; 4. Sudden infant death syndromeThe EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship
Post-Licensure Safety of the U.S. Vaccine Schedule1994 IOM report: Adverse Events Associated with Childhood Vaccines
Source: https://www.nationalacademies.org/publications/213835“The lack of adequate data regarding many of the adverse events under study was of major concern to the committee.Presentations at public meetings indicated that many parents and physicians share this concern.”DT/Td/TMeaslesMumpsOPV/IPV Hepatitis B H. influenzaetype (Hib) Vaccine Type1. Encephalopathy 2. Infantile spasms (DT only) 3. Death from SIDS (DT only)The EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship1. Guillain-Barre syndrome 2. Brachial neuritis 3. Anaphylaxis4. Anaphylaxis 5. Thrombocytopenia (MMR) 6. Anaphylaxis (MMR)7. Death from measles vaccine-strain viral infection1. Residual seizure disorder than infantile spasms 2. Demyelinating diseases of the central nervous system 3. Mononeuropathy4. Arthritis5. Erythema maltiforme6. Encephalopathy 7. Subacute sclerosing panencephalitis central nervous system 8. Residual seizure9. Sensorineural deafness (MMR) 10. Optic neuritis11. Transverse-myelitis12. Guillain-Barre syndrome 13. Thrombocytopenia14. Insulin-dependent diabetes mellitus15. Neuropathy16. Residual seizure disorder 17. Encephalopathy 18. Aseptic meningitis 19. Sensorineural deafness (MMR) 20. Insulin-dependent diabetes mellitus21. Sterility22. Thrombocytopenia23. Anaphylaxis24. Encephalopathy25. Subacute sclerosing panencephalitis26. Residual seizure 27. Sensorineural deafness (MMR) 28. Optic neuritis29. Transverse-myelitis30. Guillain-Barre syndrome31. Thrombocytopenia32. Insulin-dependent diabetes mellitus8. Guillain-Barre syndrome (OPV) 9. Poliomyelitis in recipient or contact (OPV) 10. Death from polio 11. Anaphylaxis33. Guillain-Barre syndrome34. Demyelinating diseases of the central nervous system35. Arthritis36. Death from SIDS12. Early-onset H. influenzae b disease in children age 18 months or older who receive their first Hib immunization with unconjugated PRP vaccine37. Guillain-Barre syndrome38. Transverse myelitis39. Thrombocytopenia40. Anaphylaxis41. Death from SIDS4. Early onset H. influenzae disease (conjugate vaccines)
Post-Licensure Safety of the U.S. Vaccine Schedule2012 IOM report: Adverse Effects of Vaccines: Evidence and Causality
Source: https://www.nationalacademies.org/projects/PHPH-H-08-17-A/publication/13164 362624232312 108 8Hep BDTaP/Tdap/TD/TdInfluenzaMMRHPVVaricellaHep AMeningococcal01220 0 0011251501Vaccine TypeThe EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship
Total516134
Post-Licensure Safety of the U.S. Vaccine ScheduleCombined Results of the IOM Reports
Source: https://www.nationalacademies.org/publications/1815; https://www.nationalacademies.org/publications/2138; https://www.nationalacademies.org/projects/PHPH-H-08-17-A/publication/13164 374339302312109855MMRDTaP/Tdap/TD/TdHep BInfluenzaHPVVaricellaHep AMeningococcalHibOPV/IPV28020 0 001011822150113Vaccine TypeThe EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship
Total1334183
Post-Licensure Safety of the U.S. Vaccine SchedulePost-Licensure Vaccine Safety Funding Insufficient
“It is critical to examine adverse events following immunization (AEFIs) that have not been detected in clinical trials, to ascertain whether they are causally or coincidentally related to vaccination.”“Although the ACIP acknowledges the need, there are currently no resources earmarked for postauthorization safety studies beyond annual appropriations, which must be approved by Congress each year.” “[T]he budget for vaccine-safety monitoring at the CDC (which is responsible for the majority of U.S. federal efforts) has remained stagnant … at about $20 million per year” which is an “inadequate level of funding.”Source: https://www.nejm.org/doi/full/10.1056/NEJMp2402379 38
Post-Licensure Safety of the U.S. Vaccine ScheduleInjury Claimed To Have Been Most Thoroughly Studied
Source: https://www.congress.gov/99/statute/STATUTE-100/STATUTE-100-Pg3743.pdf
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Post-Licensure Safety of the U.S. Vaccine Schedule
Source: https://doi.org/10.17226/1815Injury Claimed To Have Been Most Thoroughly Studied
40
Post-Licensure Safety of the U.S. Vaccine Schedule
Source: https://doi.org/10.17226/13164
Injury Claimed To Have Been Most Thoroughly Studied
41
Post-Licensure Safety of the U.S. Vaccine Schedule
See accompanying memorandum for source and discussion.
Injury Claimed To Have Been Most Thoroughly Studied
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Post-Licensure Safety of the U.S. Vaccine ScheduleInjury claimed to have been most thoroughly studied
Source: https://ecf.nysd.uscourts.gov/doc1/127126484251
18 involving thimerosal and/or MMR1 involving antigen (not vaccine) exposure1 involving MMR, thimerosal, and DTaP43
Post-Licensure Safety of the U.S. Vaccine ScheduleInjury claimed to have been most thoroughly studied
44
Source: https://www.cdc.gov/vaccine-safety/about/autism.html
Post-Licensure Safety of the U.S. Vaccine ScheduleAdverse Reactions Manufacturers Have a Basis to Believe Are Causally RelatedFederal Law: 21 C.F.R. §201.57Package inserts for vaccines should include “only those adverse events for which there is some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event.”
Source: https://www.fda.gov/media/72139/download FDA: Guidance for Industry: Adverse Reaction Section for Labeling for Drugs and Biological Products – Content and Format: “For purposes of prescription drug labeling and this guidance, an adverse reaction … does not include all adverse events observed during use of a drug, only those for which there is some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event.” 45
Post-Licensure Safety of the U.S. Vaccine ScheduleImportance of Unexposed GroupCDC Manual for the Surveillance of Vaccine-Preventable Diseases“Because … there is a lack of an unvaccinated group for comparison in VAERS…, reports to VAERS are useful for generating hypotheses, but studies with vaccinated and unvaccinated subjects are necessary to confirm any hypotheses.”* * *Studies finding safety concerns that lack an unexposed group are often discarded. Example: DTaP and autism study. Sources: https://www.cdc.gov/surv-manual/php/table-of-contents/chapter-21-vaers.html46
Post-Licensure Safety of the U.S. Vaccine Schedule2013 IOM Vaccine Schedule Safety Review“[N]o study … compared the differences in health outcomes … between entirely unimmunized populations of children and fully immunized children. Experts who addressed the committee pointed not to a body of evidence that had been overlooked but rather to the fact that existing research has not been designed to test the entire immunization schedule. …[Also,] studies designed to examine the long-term effects of the cumulative number of vaccines or other aspects of the immunization schedule have not been conducted.”The IOM committee explained “there is no evidence that the schedule is not safe.”Source: https://www.ncbi.nlm.nih.gov/books/NBK206948/ The Childhood Immunization Schedule and Safety
47
Post-Licensure Safety of the U.S. Vaccine ScheduleUnvaccinated Children in the U.S.
* National Immunization Survey-Child estimates 1.2% of 2-year-olds in the U.S. are unvaccinated. Based on exemption rate data for school age children, at least 1% appear to remain unvaccinated.https://www.cdc.gov/mmwr/volumes/73/wr/pdfs/mm7341a3-H.pdf; https://www.cdc.gov/schoolvaxview/data/index.html 48Age(s)Unvaccinated(no vaccines) est.2 Years of Age2-17 Years of Age45,300658,000
Post-Licensure Safety of the U.S. Vaccine ScheduleCDC Surveillance Systems
See supporting memorandum for sources and discussion. * https://www.cdc.gov/vaccine-safety/media/pdfs/white-paper-safety-508.pdf 49“The current safety surveillance systems such as the VSD … already have extensive systems in place to assess short-term outcomes … [despite the fact] the childhood immunization schedule is essentially a long-term exposure, occurring over 18 to 24 months, [and hence] long-term adverse events may be more biologically plausible than short-term events.” – CDC*CDCStudy Vaccinated v. UnvaccinatedPopulationsVSDNoteVAERSV-SafeCISANONONONOEstimated to include >20,000 unvaccinated children. Deidentified data not shared with public.CDC has refused to automate capture and submission of VAERS reports.Automated but fails to list reactions of interest.Not useful for assessing safety at a population level.
Post-Licensure Safety of the U.S. Vaccine ScheduleStudies With Unvaccinated GroupsData comparing vaccinated and unvaccinated children show a consistent pattern of vaccinated children having multiple times the rate of various chronic health issues. Sampling:
50Study LinkAuthor AffiliationsFindingshttps://pmc.ncbi.nlm.nih.gov/articles/PMC7268563/ Simpson University (CA) and Institute of Medical and Scientific Inquiry (NM)Vaccination before 1year of age was associated with increased odds of developmental delays (OR=2.18, 95% CI 1.47–3.24), asthma (OR=4.49, 95% CI 2.04–9.88) and ear infections (OR=2.13, 95% CI 1.63–2.78).https://doi.org/10.1080/02772240701806501State University of New York at Stony BrookThe odds of receiving early intervention or special education services were 8.63 times as great (OR=8.63, 95% CI 3.24–22.98) for vaccinated boys as for unvaccinated boys after adjustment for confounders.https://pubmed.ncbi.nlm.nih.gov/21058170/ State University of New York at Stony BrookMale neonates vaccinated with the hepatitis B vaccine had a 3 times risk (OR=3.002, 95% CI 1.109-8.126) for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period.https://www.oatext.com/pdf/JTS-3-187.pdf Jackson State University (MS)Vaccination associated with neurodevelopmental disorders (NDD) in children born at term (OR 2.7, 95% CI: 1.2, 6.0). Vaccination and preterm birth had 5.4 times risk (95% CI: 2.5, 11.9) compared to vaccinated but non-preterm children, and 14.5 times risk (95% CI: 5.4, 38.7) compared to neither preterm nor vaccinated. https://www.oatext.com/pdf/JTS-3-186.pdf Jackson State University (MS)Vaccinated children compared to unvaccinated more likely to be been diagnosed with: allergic rhinitis (10.4% vs. 0.4%, p <0.001), other allergies (22.2% vs. 6.9%, p <0.001), eczema/ atopic dermatitis (9.5% vs. 3.6%, p = 0.035), a learning disability (5.7% vs. 1.2%, p = 0.003), ADHD (4.7% vs. 1.0%, p =0.013), ASD (4.7% vs. 1.0%, p = 0.013), any neurodevelopmental disorder (10.5% vs. 3.1%, p<0.001) and any chronic illness (44.0% vs. 25.0%, p <0.001). https://pubmed.ncbi.nlm.nih.gov/15805992/ Vanderbilt University (TN)In multiple regression analyses there were significant ( P < .0005) and dose-dependent negative relationships between vaccination refusal and self-reported asthma or hay fever only in children with no family history of the condition and, for asthma, in children with no exposure to antibiotics during infancy.
Post-Licensure Safety of the U.S. Vaccine ScheduleExamples of Generally Unreliable Studies•Comparing vaccinated children with vaccinated children•Using risk windows post-vaccination
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Post-Licensure Safety of the U.S. Vaccine ScheduleRise in Chronic DiseasesMost of the disease contributing to the increase are related to some form of immune system deregulation, including asthma, allergies, ADHD, etc., as discussed in the accompanying memorandum. Many are also disclosed in Section 6.2 of one or more vaccine package inserts.Source: https://pubmed.ncbi.nlm.nih.gov/3944229/ (https://perma.cc/NGA9-93KW) (“According to data from the National Health Interview Survey (NHIS) [1979-1981] over two million children under 17 years (3.8%) are afflicted by chronic conditions that cause some limitation of activity.”); https://pmc.ncbi.nlm.nih.gov/articles/PMC1646496/ (https://perma.cc/KN4A-94TV) (“Data from the National Health Interview Survey indicate that the prevalence of activity-limiting chronic conditions among children under age 17 years doubled between 1960 and 1981, from 1.8 to 3.8 per cent.”); https://pubmed.ncbi.nlm.nih.gov/9551003/ (https://perma.cc/JTZ5-JBNK) (Among “children younger than 18 years who were included in the 1992-1994 National Health Interview Survey … [a] significant proportion of children, estimated at 6.5% of all US children, experienced some degree of disability.”); https://www.cdc.gov/chronic-disease/about/index.html (https://perma.cc/N4GT-38L2) (“Chronic diseases are defined broadly as conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both.”).52Year(s)Percent of Childrenwith a Chronic DiseaseEarly 1980sPresent<10%>40%Year(s)Percent of Children with a Chronic Disease
Post-Licensure Safety of the U.S. Vaccine ScheduleAluminum Adjuvants
Source: https://pubmed.ncbi.nlm.nih.gov/33887692/. See memorandum for additional sources.
Finding: Six vaccines (Pentacel, Havrix, Adacel, Pedvax, Prevnar 13, Vaqta) contained a statistically significant greater quantity and four vaccines (Infanrix, Kinrix, Pediarix, and Synflorix) contained a statistically significant lower quantity of aluminum adjuvant than listed on the product’s label.53
Post-Licensure Safety of the U.S. Vaccine SchedulePost-Licensure Safety•When robust clinical trial data is not possible to obtain, robust post-licensure safety data should support recommendations.•Condition recommendations on sponsors providing any requested follow-up safety data.•Revisit recommendations regularly.
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Efficacy in Preventing Transmission: U.S. Childhood Vaccine Schedule
Efficacy of the U.S. Vaccine ScheduleTransmission
56Some live-attenuated vaccines, such as Varivax for varicella, generally prevent transmission of the target pathogen in most recipients for an extended duration post-vaccination.
Source: see accompanying memorandum. Live-Attenuated Vaccines
Efficacy of the U.S. Vaccine ScheduleTransmission
57“IPV does not prevent intestinal infection and therefore does not prevent poliovirus transmission”Source: https://www.cdc.gov/mmwr/volumes/71/wr/mm7133e2.htm Polio
Efficacy of the U.S. Vaccine ScheduleTransmission
58Source: https://www.cdc.gov/orr/polioviruscontainment/diseaseandvirus.htmPolio
Efficacy of the U.S. Vaccine ScheduleTransmission
59Source: https://pubmed.ncbi.nlm.nih.gov/24277828/ Pertussis
Efficacy of the U.S. Vaccine ScheduleTransmission
60Source: https://pubmed.ncbi.nlm.nih.gov/31333640/ Pertussis“Natural infection [with pertussis] evokes both mucosal and systemic immune responses, while aPVs [acellular pertussis vaccines] include only a systemic immune response. … Mucosal immunity is essential to prevent colonization and transmission of B. pertussis organism. Consequently, preventive measures such as aPVs that do not induce a valid mucosal response can prevent disease but cannot avoid infection and transmission. … aPV pertussis vaccines do not prevent colonization. Consequently, they do not reduce the circulation of B. pertussis and do not exert any herd immunity effect.”
Efficacy of the U.S. Vaccine ScheduleTransmission
61Source: https://pubmed.ncbi.nlm.nih.gov/29180031/Pertussis
“That vaccination does not prevent B. pertussis infection in humans, nor the circulation of the organism in human populations in any important manner, comes from the observation that the inter-epidemic intervals have not changed in a major way since the implementation of mass vaccination.”
Efficacy of the U.S. Vaccine ScheduleTransmission
62Source: https://pubmed.ncbi.nlm.nih.gov/31333640/ Pertussis“FDA’s licensure standards for vaccines do not require demonstration of the prevention of infection or transmission. … [T]he pertussis vaccines that FDA has licensed are for prevention of pertussis disease not infection with B. pertussis.” FDA is also not “convinced that there is a any widespread misconception about this.”
Efficacy of the U.S. Vaccine ScheduleTransmission
63Source: https://www.cdc.gov/acip/vaccine-recommendations/shared-clinical-decision-making.html“Unlike routine, catch-up, and risk-based recommendations … ACIP makes shared clinical decision-making recommendations when individuals may benefit from vaccination, but broad vaccination of people in that group is unlikely to have population-level impacts.”
Efficacy in Preventing Mortality:U.S. Childhood Vaccine Schedule
Efficacy of the U.S. Vaccine ScheduleBenefits
65Vaccines are intended to prevent symptoms if the vaccinee is infected with the target pathogen, thereby potentially preventing disease and mortality.
Efficacy of the U.S. Vaccine ScheduleClaimed Benefits
66Source: https://www.cdc.gov/mmwr/volumes/73/wr/mm7331a2.htm“Among children born during 1994–2023, routine childhood vaccinations will have prevented approximately 508 million cases of illness, 32 million hospitalizations, and 1,129,000 deaths”
Efficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality
67Source: https://www.cdc.gov/mmwr/preview/mmwrhtml/su6004a2.htm-Ignores all confounders, explaining “factors other than immunization (e.g., hygiene…) might have contributed to lower disease risks in recent decades, and reductions resulting from these contributions have not been incorporated into the model”-No confidence intervals-Data is unreliable-Clearance process versus peer-review
Efficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality
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U.S. Public Health Service Report
2023 MMWR Report: Claims 25,000 diphtheria deaths prevented each year between 1994 and 2023, totaling 750,000 of the 1.1 million lives.CDC Mortality Data: 634 diphtheria deaths in 1948
Source: https://stacks.cdc.gov/view/cdc/6200; https://www.cdc.gov/nchs/data/vsus/VSUS_1948_2.pdf
Efficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality
69Source: https://web.archive.org/web/20190615081539/https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/reported-cases.pdf MMWR Report: Claims 3,003 Hepatitis B deaths prevented each year between 1994 and 2023 (totaling 90,100 of the 1.1 million lives).CDC Pink Book: There were 294 deaths from Hepatitis B in 1980, the year before the first Hep B vaccine was introduced in 1981.
Efficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality
70Source: https://stacks.cdc.gov/view/cdc/6200; https://web.archive.org/web/20190615081539/https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/reported-cases.pdf
2023 MMWR Report: claims 2,833 measles deaths prevented each year between 1994 and 2023 (totaling 85,000 of the 1.1 million lives)CDC Mortality Data: 407 measles deaths in 1962 after an over 98% decline in mortality between 1900 and 1962U.S. Public Health Service Report
Efficacy of the U.S. Vaccine ScheduleClaimed Benefit: Mortality
71Studies on non-specific effects on mortality in children: live v. non-live vaccines and developed v. developing countries
Efficacy of the U.S. Vaccine ScheduleClaimed Benefit: Mortality
72Source: https://pubmed.ncbi.nlm.nih.gov/26122188/
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Efficacy of the U.S. Vaccine Schedule
73Pneumococcal deaths are during childhood. Mortality data for: diphtheria, pertussis, and tetanus (https://www.cdc.gov/nchs/data/vsus/VSUS_1948_2.pdf, p.440, https://perma.cc/N2PN-5UPU);polio, measles, mumps, rubella, hepatitis B, hepatitis A, and varicella (https://web.archive.org/web/20190615081539/https:// www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/reported-cases.pdf,https://per-ma.cc/7GPK-32AC); Hib (There was an ineffective vaccine introduced in 1985 and withdrawn. After a Hib vaccine considered effective for infants was first licensedinlate 1990, the CDC in 1991 for the first time recommended a Hib vaccine for infants, and by 1992 vaccine uptake was only 28%. There were 17 deaths in 1991 from Hib, so to be conservative, this death number was doubled to 34 for the chart. See discussion regarding Hib vaccine in this chapter for sup-porting citations.); pneumococcal (“Before routine use of pneumococcal conjugate vaccine in 2000, the burden of pneumococcal disease among children younger than age 5 years was … 200 deaths from invasive pneumococcal disease.” Hence, this CDC estimate was used even though it appears inflated based on other data. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-17-pneumococcal-disease.html, https://perma.cc/6YQT-F4CA);and rotavirus and meningococcal (CDC listing, “Deaths per year in the United States prior to recommended vaccines,” for these diseases on slide 7: https://web.archive.org/web/20240518044830/https:// www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-05-19/01- COVID-Daley-508.pdf, https://perma.cc/VV9F-C77B).Claimed Benefit: MortalityDisease Year VaccineLicensedDiphtheria 634 Pertussis 1949 (DTP) 1,146 Tetanus 506 Polio 1955 1,368 Measles 1963 408 Mumps 1967 43 Rubella 1969 24 Hepatitis B 1981 294 Hib 1990 34 Hepatitis A 1995 97 Varicella 1995 124 Pneumococcal 2000 200 Meningococcal 2005 8 Rotavirus 2006 20 Number of Deaths in YearPrior to Licensure
Informed Consent & Considerations
Informed ConsentInformed Consent“Unlike routine, catch-up, and risk-based recommendations, … shared clinical decision-making recommendations are individually based and informed by a decision process between the health care provider and the patient or parent/guardian.”
75Source: https://www.cdc.gov/acip/vaccine-recommendations/shared-clinical-decision-making.html
Informed ConsentItems to Consider-Revisit prior recommendations made without robust data. -Require robust trial and, when possible, post-licensure safety data.-Liaison members should respect right of informed consent.
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