TY - JOUR
T1 - Association of differential censoring with survival and suboptimal control arms among oncology clinical trials
AU - Hsu, Eric J.
AU - Lin, Timothy A.
AU - Dabush, Dor R.
AU - McCaw, Zachary
AU - Koong, Alex
AU - Lin, Christine
AU - Abi Jaoude, Joseph
AU - Patel, Roshal
AU - Kouzy, Ramez
AU - El Alam, Molly B.
AU - Noticewala, Sonal
AU - Yang, Yumeng
AU - Sherry, Alexander D.
AU - Fuller, Clifton D.
AU - Thomas, Charles R.
AU - Tang, Chad
AU - Msaouel, Pavlos
AU - Das, Prajnan
AU - Huang, Bo
AU - Tian, Lu
AU - Sun, Ryan
AU - Lee, J. Jack
AU - Meirson, Tomer
AU - Ludmir, Ethan B.
N1 - Publisher Copyright:
© 2024 Oxford University Press. All rights reserved.
PY - 2024/6/7
Y1 - 2024/6/7
N2 - Differential censoring, which refers to censoring imbalance between treatment arms, may bias the interpretation of survival outcomes in clinical trials. In 146 phase III oncology trials with statistically significant time-to-event surrogate primary endpoints, we evaluated the association between differential censoring in the surrogate primary endpoints, control arm adequacy, and the subsequent statistical significance of overall survival results. Twenty-four (16%) trials exhibited differential censoring that favored the control arm, whereas 15 (10%) exhibited differential censoring that favored the experimental arm. Positive overall survival was more common in control arm differential censoring trials (63%) than in trials without differential censoring (37%) or with experimental arm differential censoring (47%; odds ratio ¼ 2.64, 95% confidence interval ¼ 1.10 to 7.20; P ¼ .04). Control arm differential censoring trials more frequently used suboptimal control arms at 46% compared with 20% without differential censoring and 13% with experimental arm differential censoring (odds ratio ¼ 3.60, 95% confidence interval ¼ 1.29 to 10.0; P ¼ .007). The presence of control arm differential censoring in trials with surrogate primary endpoints, especially in those with overall survival conversion, may indicate an inadequate control arm and should be examined and explained.
AB - Differential censoring, which refers to censoring imbalance between treatment arms, may bias the interpretation of survival outcomes in clinical trials. In 146 phase III oncology trials with statistically significant time-to-event surrogate primary endpoints, we evaluated the association between differential censoring in the surrogate primary endpoints, control arm adequacy, and the subsequent statistical significance of overall survival results. Twenty-four (16%) trials exhibited differential censoring that favored the control arm, whereas 15 (10%) exhibited differential censoring that favored the experimental arm. Positive overall survival was more common in control arm differential censoring trials (63%) than in trials without differential censoring (37%) or with experimental arm differential censoring (47%; odds ratio ¼ 2.64, 95% confidence interval ¼ 1.10 to 7.20; P ¼ .04). Control arm differential censoring trials more frequently used suboptimal control arms at 46% compared with 20% without differential censoring and 13% with experimental arm differential censoring (odds ratio ¼ 3.60, 95% confidence interval ¼ 1.29 to 10.0; P ¼ .007). The presence of control arm differential censoring in trials with surrogate primary endpoints, especially in those with overall survival conversion, may indicate an inadequate control arm and should be examined and explained.
UR - http://www.scopus.com/inward/record.url?scp=85195620173&partnerID=8YFLogxK
U2 - 10.1093/jnci/djae028
DO - 10.1093/jnci/djae028
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C2 - 38331394
AN - SCOPUS:85195620173
SN - 0027-8874
VL - 116
SP - 990
EP - 994
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 6
ER -