NorthWest Biotherapeutics Inc (NWBO)

[Lykiri]

Comment & Response
May 18, 2023
External Control Arms and Data Analysis Methods in Nonrandomized Trial of Patients With Glioblastoma
Jacob J. Mandel, MD1; John F. de Groot, MD2
Author Affiliations
1Department of Neurology and Neurosurgery, Baylor College of Medicine, Houston, Texas
2The University of California, San Francisco
JAMA Oncol. Published online May 18, 2023. doi:10.1001/jamaoncol.2023.1066

To the Editor
Liau et al1 report the results of a phase 3 nonrandomized controlled trial of treatment with autologous tumor lysate-loaded dendritic cell vaccination (DCVax-L) for patients with glioblastoma in comparison to non–protocol-specified contemporaneous external control patients treated with standard of care. The use of external control arms in oncology is a developing field of methodological innovation and regulatory interest. However, to date, these data have not provided pivotal support as substantive evidence of treatment effectiveness in oncology, and it is important to critique the results in that context.2 Despite efforts to match patients, the authors1 were unable to obtain patient-level data, which is a known important limitation with the use of external controls.3 Examining the matching-adjusted indirect comparison of the recurrent studies shows that half of the external control studies were missing Karnofsky Performance Score and MGMT promoter methylation data.1 Additionally, in the matching-adjusted indirect comparison for the newly diagnosed external studies pooled for prognostic factors, patients were matched based on Karnofsky Performance Score greater than 90 or less than 90 and age older than 50 years or younger than 50 years, with no explanation for why or how those specific cutoffs were chosen.

https://jamanetwork.com/journals/jamaoncology/article-abstract/2805079?resultClick=1

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