TY - JOUR
T1 - Fooled by Randomness. The Misleading Effect of Treatment Crossover in Randomized Trials of Therapies with Marginal Treatment Benefit
AU - Valentí, Vicente
AU - Jiménez-Fonseca, Paula
AU - Msaouel, Pavlos
AU - Salazar, Ramón
AU - Carmona-Bayonas, Alberto
N1 - Publisher Copyright:
© 2021 Taylor & Francis Group, LLC.
PY - 2022
Y1 - 2022
N2 - Crossover can bias clinical outcomes of randomized clinical trials by increasing the risk of both type I (false positive) and type II (false negative) errors. To show how crossover can increase type I error, we provide computer simulation and review herein illustrative examples (iniparib, olaratumab) of recently reported RCTs that demonstrated false-positive treatment efficacy signals due to crossover. The ethical issues associated with crossover are also discussed.
AB - Crossover can bias clinical outcomes of randomized clinical trials by increasing the risk of both type I (false positive) and type II (false negative) errors. To show how crossover can increase type I error, we provide computer simulation and review herein illustrative examples (iniparib, olaratumab) of recently reported RCTs that demonstrated false-positive treatment efficacy signals due to crossover. The ethical issues associated with crossover are also discussed.
KW - Crossover
KW - bias
KW - randomized clinical trials
UR - http://www.scopus.com/inward/record.url?scp=85121849394&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121849394&partnerID=8YFLogxK
U2 - 10.1080/07357907.2021.2020281
DO - 10.1080/07357907.2021.2020281
M3 - Comment/debate
C2 - 34919008
AN - SCOPUS:85121849394
SN - 0735-7907
VL - 40
SP - 184
EP - 188
JO - Cancer Investigation
JF - Cancer Investigation
IS - 2
ER -