The design and evaluation of hybrid controlled trials that leverage external data and randomization.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 10 2022
Historique:
received: 31 08 2020
accepted: 07 09 2022
entrez: 2 10 2022
pubmed: 3 10 2022
medline: 5 10 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36184621
doi: 10.1038/s41467-022-33192-1
pii: 10.1038/s41467-022-33192-1
pmc: PMC9527257
doi:

Banques de données

ClinicalTrials.gov
['NCT00003299', 'NCT00119613', 'NCT00363415', 'NCT01439568', 'NCT00453154']

Types de publication

Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5783

Subventions

Organisme : NLM NIH HHS
ID : R01 LM013352
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Steffen Ventz (S)

Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA. steffen.ventz.81@gmail.com.

Sean Khozin (S)

CancerLinQ, New York, NY, USA.

Bill Louv (B)

Project Data Sphere, Morrisville, NC, USA.

Jacob Sands (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Patrick Y Wen (PY)

Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Rifaquat Rahman (R)

Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Leah Comment (L)

Foundation Medicine, Inc, Cambridge, MA, USA.

Brian M Alexander (BM)

Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Foundation Medicine, Inc, Cambridge, MA, USA.

Lorenzo Trippa (L)

Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.

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Classifications MeSH