{
  "abstract": "Model averaging combines the predictions of several population pharmacokinetic models to support model-informed precision dosing, but how to select ensemble models remains unexplored. Using tacrolimus as a case study, we first evaluated all possible ensembles of 27 models in 37 kidney and liver transplant recipients with full pharmacokinetic profiles at occasions 1 and 5 and trough concentrations at occasions 2, 3 and 4. Models were weighted by individual objective function value. Predictive performance for the occasion 5 area under the curve was assessed with individual parameters estimated from the occasion 5 trough concentration or from occasion 1 to 4 observations. Then, seven ensembles, selected a priori from relevance and external evaluation scores or as the best-performing ensembles previously identified, were compared across ten sets of observations, from a single trough concentration to dense sampling. Mean imprecision per ensemble size reached a plateau beyond 3-4 models. The best ensembles depended on the set of observations, comprising three models with the occasion 5 trough concentration and seven or eight models with occasions 1 to 4 observations. Across all sets, the ensemble optimised on the occasion 5 trough concentration was among the most precise, and score-based ensembles remained consistently precise, whereas the ensemble optimised on occasions 1 to 4 generalised poorly. Only a limited sampling strategy at occasion 5 kept imprecision below 20% for all ensembles. The plateau effect generalised to infliximab and cefepime. Ensemble composition matters more than ensemble size. Model averaging should rely on well-chosen ensembles rather than all available models.",
  "abstract_shown": true,
  "affiliations": [
    "Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sante, environnement et travail), UMR_S 1085, F-35000 Rennes, France and FHU SUPORT, F-35000, Rennes"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "S. Baroudi"
    },
    {
      "name": "B. Franck"
    },
    {
      "name": "J.-B. Woillard"
    },
    {
      "name": "A. Destere"
    },
    {
      "name": "E. Comets"
    },
    {
      "name": "F. LEMAITRE"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dj2m0sv3e10bj.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.26363867",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363867v1.full",
  "id": "dj2m0sv3e10bj",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363867v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "pharmacology and therapeutics"
    ],
    [
      "openalex",
      "2735|Pharmaceutical studies and practices"
    ]
  ],
  "openalex": "W7215678977",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363867v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dj2m0sv3e10bj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:55Z",
      "native_id": "10.64898/2026.09.24.26363867",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.24.26363867v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:pharmacology and therapeutics",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Exploring Ensemble Selection for Model Averaging in Model-informed Precision Dosing: A Tacrolimus Case Study Extended to Cefepime and InfliximabExploring Ensemble Selection for Model Averaging in Model-informed Precision Dosing: A Tacrolimus Case Study Extended to Cefepime and Infliximab",
  "title_text": "Exploring Ensemble Selection for Model Averaging in Model-informed Precision Dosing: A Tacrolimus Case Study Extended to Cefepime and InfliximabExploring Ensemble Selection for Model Averaging in Model-informed Precision Dosing: A Tacrolimus Case Study Extended to Cefepime and Infliximab",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:55Z",
  "url": "https://research.draconitic.com/paper/dj2m0sv3e10bj",
  "venue": "medRxiv",
  "versions": []
}