{
  "cutoff": "2026-10-12",
  "note": "Selected publication milestones, not an exhaustive history or discovery priority claim.",
  "milestones": [
    {
      "pmid": "8538705",
      "year": "1996",
      "title": "A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine.",
      "doi": "10.1056/NEJM199602083340602",
      "url": "https://pubmed.ncbi.nlm.nih.gov/8538705/",
      "interpretation": "randomized pertussis-antigen prevention establishes clinical protection while comparing formulation-specific reactogenicity."
    },
    {
      "pmid": "10376617",
      "year": "1999",
      "title": "Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association.",
      "doi": "10.1016/s0140-6736(99)01239-8",
      "url": "https://pubmed.ncbi.nlm.nih.gov/10376617/",
      "interpretation": "UK MMR introduction/onset-clustering tests do not reproduce a major autism timing effect."
    },
    {
      "pmid": "11135778",
      "year": "2000",
      "title": "Individual and community risks of measles and pertussis associated with personal exemptions to immunization.",
      "doi": "10.1001/jama.284.24.3145",
      "url": "https://pubmed.ncbi.nlm.nih.gov/11135778/",
      "interpretation": "individual/community exemption analysis links lost vaccine protection to measles/pertussis risk."
    },
    {
      "pmid": "14519711",
      "year": "2003",
      "title": "Association between thimerosal-containing vaccine and autism.",
      "doi": "10.1001/jama.290.13.1763",
      "url": "https://pubmed.ncbi.nlm.nih.gov/14519711/",
      "interpretation": "matched Danish vaccine-formulation/dose comparison finds no increased autism risk from thimerosal; other developmental endpoints remain distinct."
    },
    {
      "pmid": "15877763",
      "year": "2005",
      "title": "No effect of MMR withdrawal on the incidence of autism: a total population study.",
      "doi": "10.1111/j.1469-7610.2005.01425.x",
      "url": "https://pubmed.ncbi.nlm.nih.gov/15877763/",
      "interpretation": "Yokohama ASD incidence does not fall after MMR withdrawal, with calendar/diagnostic context retained."
    },
    {
      "pmid": "19171612",
      "year": "2009",
      "title": "Neuropsychological performance 10 years after immunization in infancy with thimerosal-containing vaccines.",
      "doi": "10.1542/peds.2008-0795",
      "url": "https://pubmed.ncbi.nlm.nih.gov/19171612/",
      "interpretation": "neuropsychological follow-up after randomized infant dose-regimen assignment shows few small differences and does not directly test ASD incidence."
    },
    {
      "pmid": "20837594",
      "year": "2010",
      "title": "Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism.",
      "doi": "10.1542/peds.2010-0309",
      "url": "https://pubmed.ncbi.nlm.nih.gov/20837594/",
      "interpretation": "validated individual thimerosal exposure/ASD comparison is null; later antigen-load analysis(PMID 23545349) reuses the same parent sample."
    },
    {
      "pmid": "20587679",
      "year": "2010",
      "title": "Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures.",
      "doi": "10.1542/peds.2010-0665",
      "url": "https://pubmed.ncbi.nlm.nih.gov/20587679/",
      "interpretation": "first-doseMMRVfebrile-seizure risk is quantified against separate MMR plus varicella, demonstrating measurable formulation-specific safety effects."
    },
    {
      "pmid": "25898051",
      "year": "2015",
      "title": "Autism occurrence by MMR vaccine status among US children with older siblings with and without autism.",
      "doi": "10.1001/jama.2015.3077",
      "url": "https://pubmed.ncbi.nlm.nih.gov/25898051/",
      "interpretation": "MMR familial-risk cohort shows no increased ASD association in children with affected older siblings."
    },
    {
      "pmid": "30831578",
      "year": "2019",
      "title": "Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study.",
      "doi": "10.7326/M18-2101",
      "url": "https://pubmed.ncbi.nlm.nih.gov/30831578/",
      "interpretation": "larger Danish MMR cohort examines defined risk and postvaccination timing groups with no consistent increased ASD signal."
    },
    {
      "pmid": "34435933",
      "year": "2022",
      "title": "A randomized trial assessing the efficacy, immunogenicity, and safety of vaccination with live attenuated varicella zoster virus-containing vaccines: ten-year follow-up in Russian children.",
      "doi": "10.1080/21645515.2021.1959148",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34435933/",
      "interpretation": "ten-year varicella trial follow-up retains pathogen-specific clinical prevention, with dose and parent-trial scope."
    },
    {
      "pmid": "42520244",
      "year": "2026",
      "title": "Association Between First MMR Vaccination Before Age 2 Years and Childhood Autism in a U.S. EHR Cohort of 2.5 Million Children.",
      "doi": "10.1097/INF.0000000000005349",
      "url": "https://pubmed.ncbi.nlm.nih.gov/42520244/",
      "interpretation": "US EHR age-landmark and negative-control study adds2.56 million-child near-null MMR/ASD evidence without eliminating every possible residual bias."
    }
  ],
  "gaps": [
    "Historical ethylmercury, environmental methylmercury and MMR are different exposures; actual formulation/dose/route must be recorded.",
    "A near-null negative control limits specified bias pathways but cannot eliminate all residual confounding.",
    "Risk of very rare baseline-defined effects is bounded by precision; no responder-defined subgroup can rescue a failed broad prediction.",
    "General neuropsychological tests, tics, biomarkers and animal proxies are not incident clinical autism.",
    "Absolute net-health outcomes require linked infection, adverse-event and diagnostic follow-up rather than one favorable marker or passive-report trend.",
    "Shared registry/VSD/clinic/trial reports require study grouping and distinct error-mode assessment.",
    "Safety surveillance should preserve known formulation/age-specific adverse events and baseline clinical contraindications."
  ],
  "decisive_experiment": "Pre-register a target-trial emulation of existing naturally varying vaccine timing or historical matched formulations without withholding recommended vaccination. Define eligibility and familial risk before outcomes, validate exposure and incident diagnosis, use correct time-at-risk and age landmarks, measure healthcare contact and independent negative controls, and link confirmed infection, serious morbidity and specific adverse events over a stated horizon. Independently replicate absolute net outcomes and proposed dose predictions; no responder-only or postdiagnosis susceptibility scope."
}