Leveraging external data in the design and analysis of clinical trials in neuro-oncology

Rifaquat Rahman; Steffen Ventz; Jon McDunn; Bill Louv; Irmarie Reyes-Rivera; Mei-Yin C Polley; Fahar Merchant; Lauren E Abrey; Joshua E Allen; Laura K Aguilar; Estuardo Aguilar-Cordova; David Arons; Kirk Tanner; Stephen Bagley; Mustafa Khasraw; Timothy Cloughesy; Patrick Y Wen; Brian M Alexander; Lorenzo Trippa

doi:10.1016/S1470-2045(21)00488-5

Leveraging external data in the design and analysis of clinical trials in neuro-oncology

Lancet Oncol. 2021 Oct;22(10):e456-e465. doi: 10.1016/S1470-2045(21)00488-5.

Authors

Rifaquat Rahman¹, Steffen Ventz², Jon McDunn³, Bill Louv³, Irmarie Reyes-Rivera⁴, Mei-Yin C Polley⁵, Fahar Merchant⁶, Lauren E Abrey⁷, Joshua E Allen⁸, Laura K Aguilar⁹, Estuardo Aguilar-Cordova⁹, David Arons¹⁰, Kirk Tanner¹⁰, Stephen Bagley¹¹, Mustafa Khasraw¹², Timothy Cloughesy¹³, Patrick Y Wen¹⁴, Brian M Alexander¹⁵, Lorenzo Trippa²

Affiliations

¹ Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
² Department of Data Sciences, Dana-Farber Cancer Institute, Harvard T H Chan School of Public Health, Boston, MA, USA.
³ Project Data Sphere, Morrisville, NC, USA.
⁴ F Hoffmann-La Roche, Basel, Switzerland.
⁵ Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
⁶ Medicenna Therapeutics, Toronto, ON, Canada.
⁷ Novartis, Basel, Switzerland.
⁸ Chimerix, Durham, NC, USA.
⁹ Candel Therapeutics, Needham, MA, USA.
¹⁰ National Brain Tumor Society, Newton, MA, USA.
¹¹ Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹² Department of Neurosurgery, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
¹³ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
¹⁴ Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard T H Chan School of Public Health, Boston, MA, USA.
¹⁵ Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA; Foundation Medicine, Cambridge, MA, USA.

Abstract

Integration of external control data, with patient-level information, in clinical trials has the potential to accelerate the development of new treatments in neuro-oncology by contextualising single-arm studies and improving decision making (eg, early stopping decisions). Based on a series of presentations at the 2020 Clinical Trials Think Tank hosted by the Society of Neuro-Oncology, we provide an overview on the use of external control data representative of the standard of care in the design and analysis of clinical trials. High-quality patient-level records, rigorous methods, and validation analyses are necessary to effectively leverage external data. We review study designs, statistical methods, risks, and potential distortions in using external data from completed trials and real-world data, as well as data sources, data sharing models, ongoing work, and applications in glioblastoma.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use*
Brain Neoplasms / drug therapy*
Brain Neoplasms / pathology
Controlled Clinical Trials as Topic*
Glioblastoma / drug therapy*
Glioblastoma / pathology
Humans
Information Dissemination
Medical Oncology*
Neurology*
Research Design*
Treatment Outcome

Substances

Antineoplastic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding