PMID- 34479210
OWN - NLM
STAT- MEDLINE
DCOM- 20220321
LR  - 20220321
IS  - 1540-1413 (Electronic)
IS  - 1540-1405 (Linking)
VI  - 19
IP  - 12
DP  - 2021 Sep 3
TI  - Quantifying Withdrawal of Consent, Loss to Follow-Up, Early Drug Discontinuation, 
      and Censoring in Oncology Trials.
PG  - 1433-1440
LID - jnccn20615 [pii]
LID - 10.6004/jnccn.2021.7015 [doi]
AB  - BACKGROUND: Censoring due to early drug discontinuation (EDD) or withdrawal of 
      consent or loss to follow-up (WCLFU) can result in postrandomization bias. In 
      oncology, censoring rules vary with no defined standards. In this study, we 
      sought to describe the planned handling and transparency of censoring data in 
      oncology trials supporting FDA approval and to compare EDD and WCLFU in 
      experimental and control arms. METHODS: We searched FDA archives to identify 
      solid tumor drug approvals and their associated trials between 2015 and 2019, and 
      extracted the planned handling and reporting of censored data. We compared the 
      proportion of WCLFU and EDD between the experimental and control arms by using 
      generalized estimating equations, and performed logistic regression to identify 
      trial characteristics associated with WCLFU occurring more frequently in the 
      control group. RESULTS: Censoring rules were defined adequately in 48 (59%) of 81 
      included studies. Only 14 (17%) reported proportions of censored participants 
      clearly. The proportion of WCLFU was higher in the control group than in the 
      experimental group (mean, 3.9% vs 2.5%; beta-coefficient, -2.2; 95% CI, -3.1 to 
      -1.3; P<.001). EDD was numerically higher in the experimental arm in 61% of 
      studies, but there was no statistically significant difference in the proportion 
      of EDD between the experimental and control groups (mean, 21.6% vs 19.9%, 
      respectively; beta-coefficient, 0.27; 95% CI, -0.32 to 0.87; P=.37). The proportion 
      of EDD due to adverse effects (AEs) was higher in the experimental group (mean, 
      13.2% vs 8.5%; beta-coefficient, 1.5; 95% CI, 0.57-2.45; P=.002). WCLFU was higher 
      in the control group in studies with an active control group (odds ratio [OR], 
      10.1; P<.001) and in open label studies (OR, 3.00; P=.08). CONCLUSIONS: There are 
      significant differences in WCLFU and EDD for AEs between the experimental and 
      control arms in oncology trials. This may introduce postrandomization bias. 
      Trials should improve the reporting and handling of censored data so that 
      clinicians and patients are fully informed regarding the expected benefits of a 
      treatment.
FAU - Wilson, Brooke E
AU  - Wilson BE
AD  - 1Division of Medical Oncology & Hematology, Department of Medicine, Princess 
      Margaret Cancer Centre, and University of Toronto, Toronto, Ontario, Canada; and.
AD  - 2University of New South Wales, Kensington, New South Wales, Australia.
FAU - Nadler, Michelle B
AU  - Nadler MB
AD  - 1Division of Medical Oncology & Hematology, Department of Medicine, Princess 
      Margaret Cancer Centre, and University of Toronto, Toronto, Ontario, Canada; and.
FAU - Desnoyers, Alexandra
AU  - Desnoyers A
AD  - 1Division of Medical Oncology & Hematology, Department of Medicine, Princess 
      Margaret Cancer Centre, and University of Toronto, Toronto, Ontario, Canada; and.
FAU - Amir, Eitan
AU  - Amir E
AD  - 1Division of Medical Oncology & Hematology, Department of Medicine, Princess 
      Margaret Cancer Centre, and University of Toronto, Toronto, Ontario, Canada; and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210903
PL  - United States
TA  - J Natl Compr Canc Netw
JT  - Journal of the National Comprehensive Cancer Network : JNCCN
JID - 101162515
SB  - IM
MH  - Drug Approval
MH  - Follow-Up Studies
MH  - Humans
MH  - *Neoplasms/drug therapy
MH  - Odds Ratio
EDAT- 2021/09/04 06:00
MHDA- 2022/03/22 06:00
CRDT- 2021/09/03 20:29
PHST- 2020/11/08 00:00 [received]
PHST- 2021/01/23 00:00 [accepted]
PHST- 2021/09/04 06:00 [pubmed]
PHST- 2022/03/22 06:00 [medline]
PHST- 2021/09/03 20:29 [entrez]
AID - jnccn20615 [pii]
AID - 10.6004/jnccn.2021.7015 [doi]
PST - epublish
SO  - J Natl Compr Canc Netw. 2021 Sep 3;19(12):1433-1440. doi: 
      10.6004/jnccn.2021.7015.