{
  "abstract": "Background: Defining outcomes completely before conducting clinical trials helps to mitigate concerns about reporting biases; however, there is limited guidance to help investigators define outcomes completely. Methods: Building on a previous framework, we developed guidance for defining trial outcomes completely and consistently. We reviewed literature, developed preliminary guidance, and refined guidance iteratively through pilot testing. We randomly selected 225 randomized controlled trials (RCTs) from ClinicalTrials.gov, which evaluated 3,424 outcomes. Two raters followed a structured approach to define each outcome. When raters encountered outcomes they could not define, we refined our guidance. We continued this process until no further changes were needed. We finalized the guidance through multiple drafts and discussions among authors. Findings: In clinical trials, a completely defined outcome includes six elements: outcome domain, specific measurement, specific metric, cutoff (if applicable), variable type, and time point. We developed guidance for naming specific measurements for both subjective and objective outcomes. We expanded on prior work by describing more comprehensive categories for specific metrics. To be consistent with the estimand framework, we replaced “method of aggregation” with two distinct elements that describe values in individuals (rather than summary measures): “variable type” and “cutoff.” We further defined “cutoff” with three sub-elements, and we defined “variable type” as whether the value for each individual is continuous or categorical. Conclusions: Trialists and sponsors could use this framework and guidance to define outcomes in trial registrations, protocols, and results reports. When all six elements are defined, readers can better determine whether reported outcomes were prespecified and whether different trials assessed the same outcomes. Why was this study done?: What did the researchers do and find?: What do these findings mean?: In this Guidelines and Guidance article, Xiangji Ying and colleagues provide updated guidance—including a six-element framework with worked examples—for defining outcomes completely and consistently in clinical trials.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, United States of America",
    "Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America",
    "Methods in Evidence Synthesis Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia",
    "Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, Indiana, United States of America",
    "Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America",
    "Arkansas Children’s Research Institute, Little Rock, Arkansas, United States of America",
    "Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom",
    "Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America",
    "Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada",
    "Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada",
    "Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, United States of America",
    "School of Information Sciences, University of Illinois Urbana-Champaign, Champaign, Illinois, United States of America"
  ],
  "article_type": "Guidelines and Guidance",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiangji Ying",
      "orcid": "0000-0002-1713-3788"
    },
    {
      "affs": [
        1
      ],
      "name": "Tianjing Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Joanne E. McKenzie",
      "orcid": "0000-0003-3534-1641"
    },
    {
      "affs": [
        2
      ],
      "name": "Matthew J. Page",
      "orcid": "0000-0002-4242-7526"
    },
    {
      "affs": [
        0
      ],
      "name": "Kiran Ninan",
      "orcid": "0000-0002-8085-6751"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Pierre Oberste",
      "orcid": "0009-0003-2075-5267"
    },
    {
      "affs": [
        3
      ],
      "name": "Colby J. Vorland",
      "orcid": "0000-0003-4225-372X"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Andrew W. Brown",
      "orcid": "0000-0002-1758-8205"
    },
    {
      "affs": [
        1
      ],
      "name": "Riaz Qureshi",
      "orcid": "0000-0002-6670-4874"
    },
    {
      "affs": [
        6
      ],
      "name": "Nicholas J. DeVito",
      "orcid": "0000-0001-8286-1995"
    },
    {
      "affs": [
        7
      ],
      "name": "Ian J. Saldanha",
      "orcid": "0000-0002-2062-3382"
    },
    {
      "affs": [
        8
      ],
      "name": "Martin Offringa",
      "orcid": "0000-0002-4402-5299"
    },
    {
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        8,
        9
      ],
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      "orcid": "0000-0002-5152-0108"
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    {
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        10
      ],
      "name": "Sirui Zhang",
      "orcid": "0009-0002-8410-436X"
    },
    {
      "affs": [
        2
      ],
      "name": "Phi-Yen Nguyen",
      "orcid": "0000-0002-0476-3385"
    },
    {
      "affs": [
        11
      ],
      "name": "Joe Menke",
      "orcid": "0000-0002-7374-7549"
    },
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      "affs": [
        8
      ],
      "name": "Veronica Ka Wai Lai",
      "orcid": "0000-0003-3593-9141"
    },
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      ],
      "name": "Halil Kilicoglu",
      "orcid": "0000-0003-3987-9393"
    },
    {
      "affs": [
        0
      ],
      "name": "Evan Mayo-Wilson",
      "orcid": "0000-0001-6126-2459"
    }
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