The design and evaluation of hybrid controlled trials that leverage external data and randomization Article Swipe
Steffen Ventz
,
Sean Khozin
,
Bill Louv
,
Jacob Sands
,
Patrick Y. Wen
,
Rifaquat Rahman
,
Leah A. Comment
,
Brian M. Alexander
,
Lorenzo Trippa
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-022-33192-1
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-022-33192-1
Patient-level data from completed clinical studies or electronic health records can be used in the design and analysis of clinical trials. However, these external data can bias the evaluation of the experimental treatment when the statistical design does not appropriately account for potential confounders. In this work, we introduce a hybrid clinical trial design that combines the use of external control datasets and randomization to experimental and control arms, with the aim of producing efficient inference on the experimental treatment effects. Our analysis of the hybrid trial design includes scenarios where the distributions of measured and unmeasured prognostic patient characteristics differ across studies. Using simulations and datasets from clinical studies in extensive-stage small cell lung cancer and glioblastoma, we illustrate the potential advantages of hybrid trial designs compared to externally controlled trials and randomized trial designs.
Related Topics
Concepts
Clinical trial
Clinical study design
Computer science
Leverage (statistics)
Randomization
Research design
Inference
Confounding
Randomized controlled trial
Design of experiments
Restricted randomization
Data mining
Medicine
Medical physics
Machine learning
Artificial intelligence
Statistics
Mathematics
Surgery
Pathology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41467-022-33192-1
- https://www.nature.com/articles/s41467-022-33192-1.pdf
- OA Status
- gold
- Cited By
- 24
- References
- 38
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4300003117
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4300003117Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41467-022-33192-1Digital Object Identifier
- Title
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The design and evaluation of hybrid controlled trials that leverage external data and randomizationWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-10-02Full publication date if available
- Authors
-
Steffen Ventz, Sean Khozin, Bill Louv, Jacob Sands, Patrick Y. Wen, Rifaquat Rahman, Leah A. Comment, Brian M. Alexander, Lorenzo TrippaList of authors in order
- Landing page
-
https://doi.org/10.1038/s41467-022-33192-1Publisher landing page
- PDF URL
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https://www.nature.com/articles/s41467-022-33192-1.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://www.nature.com/articles/s41467-022-33192-1.pdfDirect OA link when available
- Concepts
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Clinical trial, Clinical study design, Computer science, Leverage (statistics), Randomization, Research design, Inference, Confounding, Randomized controlled trial, Design of experiments, Restricted randomization, Data mining, Medicine, Medical physics, Machine learning, Artificial intelligence, Statistics, Mathematics, Surgery, PathologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
24Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 14, 2024: 4, 2023: 5, 2022: 1Per-year citation counts (last 5 years)
- References (count)
-
38Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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