_quarto-dfda-spec.yml

project:
  type: website
  output-dir: _site/dfda-spec
  execute-dir: project
  resources:
    - knowledge/data/
    - assets/
    - _redirects
    - robots.txt
    - llms.txt
  render:
    # Paper is copied to index.qmd by render script
    - index.qmd
    - knowledge/appendix/parameters-and-calculations.qmd

# Custom fields for render-quarto.py
dih-render:
  emoji: "🔬"
  index-source: knowledge/appendix/dfda-spec-paper.qmd
  fallback-404-redirect-domain: https://manual.WarOnDisease.org  # Redirects here if path doesn't exist on this site
  pdf-output-file: dfda-spec-paper.pdf
  netlify-site-id: "01e9af64-b6d0-48ee-8c3d-43994745ac3f"
  netlify-cname: "dfda-spec-warondisease-org.netlify.app"
  show-confidence-intervals: true  # Show 95% CI ranges for calculated values in academic papers
  concept-terms:
    - term: "decentralized FDA"
      aliases:
        - "dFDA"
        - "decentralized framework for drug assessment"
      manual-target: knowledge/solution/dfda.qmd
      citation-keys:
        - dfda-spec-paper-2025
        - dfda-impact-paper-2025
    - term: "Continuous Evidence Generation Protocol"
      aliases:
        - "CEGP"
        - "Two-Stage Validation"
  # Image generation prompts (used by scripts/images/generate-project-branding-images.ts)
  favicon-prompt: "Pill/capsule inside a magnifying glass."

profiles:
  default:
    dotenv:
      allowEmptyValues: true

author:
  - name: Mike P. Sinn
    email: m@warondisease.org
    orcid: 0009-0006-0212-1094
    affiliations:
      - name: "Institute for Accelerated Medicine"
        url: https://acceleratedmedicine.org

website:
  title: "The Continuous Evidence Generation Protocol: Two-Stage Validation (RWE → Pragmatic Trials)"
  description: 'We present the Predictor Impact Score (PIS), a novel composite metric operationalizing Bradford Hill causality criteria for automated signal detection from aggregated N-of-1 observational studies. Combined with pragmatic trial confirmation (based on evidence from 108+ embedded trials), this two-stage framework would generate validated outcome labels at 44.1x lower cost than traditional Phase III trials. This enables continuous, population-scale pharmacovigilance and precision dosing recommendations.'
  site-url: https://manual.warondisease.org/knowledge/appendix/dfda-spec-paper.html
  favicon: assets/icons/dfda-favicon.png
  page-navigation: true
  page-footer:
    left: "© 2025 [Institute for Accelerated Medicine](https://acceleratedmedicine.org) | [CC BY-NC 4.0](https://creativecommons.org/licenses/by-nc/4.0/)"
    center: "[PDF](https://manual.warondisease.org/knowledge/appendix/dfda-spec-paper.pdf) | [All Papers](https://manual.warondisease.org/knowledge/papers.html)"
    right: "[VOTE](https://WarOnDisease.org)"
  navbar:
    right:
      - text: "Prototype"
        href: https://dfda.earth
      - text: "Calculations"
        href: knowledge/appendix/parameters-and-calculations.qmd
      - text: "VOTE"
        href: https://WarOnDisease.org

execute:
  fig-path: "knowledge/figures/"
  cache: false
  freeze: auto  # Only re-run cells when content changes
  daemon: 300
  daemon-restart: false
  env:
    PYTHONPATH: "."

metadata:
  importance: 78
  creator: "Mike P. Sinn"
  orcid: "0009-0006-0212-1094"
  primary-author: "Mike P. Sinn"
  byline: "Mike P. Sinn"
  human-author: "Mike P. Sinn"
  author-email: "mike@warondisease.org"
  author-url: "https://mikesinn.com"
  author-website: "https://mikesinn.com"
  contact: "mike@warondisease.org"
  language: "en-US"
  subject: "Pharmacovigilance, Real-World Evidence, N-of-1 Trials, Causal Inference, Statistical Methods"
  category: "Academic Paper, Medical Research, Methodology"
  coi-statement: "The author declares no competing interests. The author does maintain a bias toward the Bradford Hill criteria producing correct answers, which some regulatory agencies may find disruptive."
  data-availability: "All data and code used in this analysis are publicly available at https://github.com/wishonia/earth-optimization-protocol"
  ethics-statement: "This research did not involve human subjects. It proposes a framework that would involve considerably more of them, but with their informed consent and at 44x lower cost."
  funding: "This research received no funding. The statistical framework described herein costs less to develop than a single traditional Phase III trial costs to delay."
  github-profile: "https://github.com/mikepsinn"
  linkedin: "https://www.linkedin.com/in/mikesinn"
  orcid-url: "https://orcid.org/0009-0006-0212-1094"
  google-scholar: "https://scholar.google.com/citations?user=RjDd_qcAAAAJ"
  keywords:
    - dfda
    - predictor-impact-score
    - pharmacovigilance
    - real-world-evidence
    - n-of-1-trials
    - causal-inference
    - bradford-hill-criteria
    - treatment-effects
    - adverse-events
    - outcome-labels
    - statistical-methods
    - dfda
    - decentralized-fda
  version: "0.9"
  edition: "Working Draft"
  copyright: "© 2025 The Institute for Accelerated Medicine"
  copyright-year: "2025"
  license: "CC BY-NC 4.0"
  license-url: "https://creativecommons.org/licenses/by-nc/4.0/"
  rights: "Creative Commons Attribution-NonCommercial 4.0 International License"
  publisher: "Institute for Accelerated Medicine"
  publisher-url: "https://acceleratedmedicine.org"
  publisher-name: "Mike P. Sinn"
  publisher-email: "mike@warondisease.org"
  repo-url: "https://github.com/wishonia/earth-optimization-protocol"
  issue-url: "https://github.com/wishonia/earth-optimization-protocol/issues"
  source-url: "https://github.com/wishonia/earth-optimization-protocol"
  geographic-coverage: "Global"
  audience: "Researchers, Regulatory Scientists, Biostatisticians, Pharmacoepidemiologists, Health Data Scientists"
  format: "Working Paper"
  type: "Academic"
  genre: "Biostatistics, Pharmacoepidemiology, Methodology"
  medium: "Digital"
  twitter-site: "https://x.com/warondisease"
  twitter-creator: "https://x.com/warondisease"
  og-site-name: "Decentralized FDA"

  # Identifiers
  # Zenodo Concept DOI (stable across all versions - use for citations and new versions)
  doi: "10.5281/zenodo.18203375"

  # Open Graph metadata (enables per-page custom OG images)
  open-graph: true
  image: "https://manual.warondisease.org/assets/og/dfda-spec-og-1200x630.jpg"

  # Publication tracking
  publishing:
    own-site:
      url: "https://manual.warondisease.org/knowledge/appendix/dfda-spec-paper.html"
      status: deployed
    preprints:
      - platform: zenodo
        status: auto-uploaded
        url: "https://zenodo.org/record/18522034"
        doi: "10.5281/zenodo.18203375"
      - platform: medrxiv
        status: pending
        url: ""
      - platform: arxiv
        status: pending
        category: stat.ME
    journals:
      - name: "Clinical Pharmacology & Therapeutics"
        tier: 2
        status: target
        url: ""
      - name: "Pharmacoepidemiology and Drug Safety"
        tier: 2
        status: target
        url: ""
      - name: "Drug Safety"
        tier: 2
        status: target
        url: ""

# Remove "Appendix" prefix
language:
  crossref-apx-prefix: ""
  section-title-appendices: ""

# Bibliography: Single source of truth for all citations
bibliography: references.bib
csl: nature-annotated.csl  # Renders 'abstract' field (quotes) in bibliography

jupyter: dih-project-kernel

format:
  html:
    lightbox: auto
    theme:
      - cosmo
    mermaid:
      theme: neutral
    echo: false
    number-sections: true
    toc: true
    toc-depth: 3
    css:
      - styles.css
      - economics-overrides.css
    include-before-body:
      - file: assets/html/page-loader.html
    include-after-body:
      - file: assets/html/site-enhancements-loader.html
    include-in-footer:
      - file: assets/html/generated-footer.html
    include-in-header:
      - text: |
          <!-- Icons (project-specific) -->
          <link rel="icon" type="image/png" sizes="32x32" href="/assets/icons/dfda-favicon-32x32.png">
          <link rel="icon" type="image/png" sizes="16x16" href="/assets/icons/dfda-favicon-16x16.png">
          <link rel="apple-touch-icon" sizes="180x180" href="/assets/icons/dfda-apple-touch-icon.png">
          <link rel="icon" type="image/png" sizes="192x192" href="/assets/icons/dfda-android-chrome-192x192.png">
          <link rel="icon" type="image/png" sizes="512x512" href="/assets/icons/dfda-android-chrome-512x512.png">
      - file: assets/html/google-analytics.html
      - file: assets/html/hypothesis.html
      - file: assets/html/fonts-preload.html
    citation-hover: true
    code-fold: true
    link-citations: true
    smooth-scroll: true
    code-tools: false
    filters: [assets/filters/live-version-note.lua]
  pdf:
    output-file: "dfda-spec-paper.pdf"
    documentclass: article
    institute: "Institute for Accelerated Medicine"
    echo: false
    toc: true
    toc-depth: 3
    number-sections: true
    colorlinks: true
    link-citations: true
    date: ""
    include-in-header:
      - callout-bw.tex
      - institute-header.tex
      - text: |
          \paperurl{https://manual.warondisease.org/knowledge/appendix/dfda-spec-paper.html}
    geometry:
      - top=1in
      - bottom=1in
      - left=1in
      - right=1in
    fontsize: 11pt
    filters: [assets/filters/live-version-note.lua]