TY  - JOUR
AU  - Edelmann, Dominic
AU  - Terzer, Tobias
AU  - Horak, Peter
AU  - Schlenk, Richard
AU  - Benner, Axel
TI  - The Progression-Free-Survival Ratio in Molecularly Aided Tumor Trials: A Critical Examination of Current Practice and Suggestions for Alternative Methods.
JO  - Biometrical journal
VL  - 67
IS  - 1
SN  - 0323-3847
CY  - Berlin
PB  - Wiley-VCH
M1  - DKFZ-2024-02737
SP  - e70028
PY  - 2025
N1  - #EA:C060#LA:C060#
AB  - The progression-free-survival ratio is a popular endpoint in oncology trials, which is frequently applied to evaluate the efficacy of molecularly targeted treatments in late-stage patients. Using elementary calculations and simulations, numerous shortcomings of the current methodology are pointed out. As a remedy to these shortcomings, an alternative methodology is proposed, using a marginal Cox model or a marginal accelerated failure time model for clustered time-to-event data. Using comprehensive simulations, it is shown that this methodology outperforms existing methods in settings where the intrapatient correlation is low to moderate. The performance of the model is further demonstrated in a real data example from a molecularly aided tumor trial. Sample size considerations are discussed.
KW  - Humans
KW  - Biometry: methods
KW  - Neoplasms: mortality
KW  - Clinical Trials as Topic: methods
KW  - Progression-Free Survival
KW  - Molecular Targeted Therapy: methods
KW  - Models, Statistical
KW  - Proportional Hazards Models
KW  - Weibull distribution (Other)
KW  - accelerated failure time model (Other)
KW  - growth modulation index (Other)
KW  - marginal model (Other)
KW  - paired time‐to‐event data (Other)
KW  - progression‐free‐survival ratio (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39692541
DO  - DOI:10.1002/bimj.70028
UR  - https://inrepo02.dkfz.de/record/295924
ER  -