{
  "abstract": "Correctly evaluating how vaccine efficacy (VE) changes over time is important for understanding long-term protection and guiding vaccination strategies. Using the 18-month pre-booster data from the multi-center RTS,S/AS01 malaria vaccine trial, we examined how different approaches of modeling time-varying VE affect the interpretation of vaccine protection. Four commonly used linear-in-parameter functions and a four-parameter monotonic function were evaluated and compared with semi-parametric spline benchmarks. Across study sites, the four-parameter function was favored when a sufficient number of clinical malaria episodes were observed. Different VE specifications led to substantially different estimates of vaccine impact under a seasonal delivery strategy. Across settings with a sufficient number of episodes, the four-parameter model recovered an inverse-sigmoid pattern of RTS,S/AS01 protection over 18 months, with rapid early decline followed by stabilization at 20-40%. These findings show that modeling choices influence interpretation of vaccine protection and support the four-parameter approach as a parsimonious, biologically-interpretable parametric form for characterizing waning VE in the RTS,S/AS01 setting, with broader applicability across other vaccine platforms requiring further evaluation.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Biomedical Data Science, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore",
    "Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK",
    "Signature Programme in Health Services & Systems Research, Duke-NUS Medical School, Singapore, Singapore",
    "Tampere Center for Child, Adolescent and Maternal Health Research, Tampere University, Tampere, Finland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ziwei Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Paul Milligan"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Yin Bun Cheung"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f9nm6raqznv58.bib",
  "cited_by": 0,
  "doi": "10.1038/s41541-026-01519-4",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696702/",
  "id": "f9nm6raqznv58",
  "issns": [
    "2059-0105"
  ],
  "landing_url": "https://doi.org/10.1038/s41541-026-01519-4",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2739|Malaria Research and Control"
    ]
  ],
  "openalex": "W7167231286",
  "pdf_url": "https://www.nature.com/articles/s41541-026-01519-4_reference.pdf",
  "pmcid": "PMC13696702",
  "pmid": "42399666",
  "published": "2026-07-03",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/f9nm6raqznv58.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:00Z",
      "native_id": "PMC13696702",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41541-026-01519-4"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Malaria Research and Control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Modeling time-varying efficacy of RTS,S/AS01 malaria vaccine across trial settings",
  "title_text": "Modeling time-varying efficacy of RTS,S/AS01 malaria vaccine across trial settings",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:59Z",
  "url": "https://research.draconitic.com/paper/f9nm6raqznv58",
  "venue": "NPJ Vaccines",
  "versions": []
}