Association of differential censoring with survival and suboptimal control arms among oncology clinical trials

Eric J Hsu; Timothy A Lin; Dor R Dabush; Zachary McCaw; Alex Koong; Christine Lin; Joseph Abi Jaoude; Roshal Patel; Ramez Kouzy; Molly B El Alam; Sonal Noticewala; Yumeng Yang; Alexander D Sherry; Clifton D Fuller; Charles R Thomas Jr; Chad Tang; Pavlos Msaouel; Prajnan Das; Bo Huang; Lu Tian; Ryan Sun; J Jack Lee; Tomer Meirson; Ethan B Ludmir

doi:10.1093/jnci/djae028

Association of differential censoring with survival and suboptimal control arms among oncology clinical trials

J Natl Cancer Inst. 2024 Feb 9:djae028. doi: 10.1093/jnci/djae028. Online ahead of print.

Authors

Eric J Hsu¹, Timothy A Lin^{2

3}, Dor R Dabush⁴, Zachary McCaw⁵, Alex Koong², Christine Lin², Joseph Abi Jaoude², Roshal Patel², Ramez Kouzy², Molly B El Alam², Sonal Noticewala², Yumeng Yang⁶, Alexander D Sherry², Clifton D Fuller², Charles R Thomas Jr⁷, Chad Tang², Pavlos Msaouel⁸, Prajnan Das², Bo Huang⁹, Lu Tian¹⁰, Ryan Sun¹¹, J Jack Lee¹¹, Tomer Meirson^{4

12}, Ethan B Ludmir^{2

11}

Affiliations

¹ Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
² Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel.
⁵ Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁶ School of Bioinformatics, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁷ Radiation Oncology, Dartmouth Cancer Center, Geisel School of Medicine, Lebanon, NH, USA.
⁸ Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Pfizer Inc, Groton, CT, USA.
¹⁰ Department of Health Research and Policy, Stanford University, Stanford, CA, USA.
¹¹ Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹² Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

PMID: 38331394
DOI: 10.1093/jnci/djae028

Abstract

Differential censoring (DC), referring to censoring imbalance between treatment arms, may bias the interpretation of survival outcomes in clinical trials. In 146 phase 3 oncology trials with statistically significant time-to-event surrogate primary endpoints (PEPs), we evaluated the association between DC in the surrogate PEP, control arm adequacy, and the subsequent statistical significance of OS results. Twenty-four (16%) trials exhibited DC favoring the control arm (ConDC), while 15 (10%) exhibited experimental arm DC (ExpDC). Positive OS was more common in ConDC trials (63%) than trials without DC (37%) or with ExpDC (47%; odds ratio [OR] 2.64, 95% CI 1.10-7.20; P=.04). ConDC trials more frequently used suboptimal control arms (46%) compared to 20% without DC and 13% with ExpDC (OR 3.60, 95% CI 1.29-10.0; P=.007). The presence of ConDC in trials with surrogate PEPs, especially in those with OS conversion, may indicate an inadequate control arm and should be examined and explained.