Cancer Epidemiol. 2026 Feb 26;102:103016. doi: 10.1016/j.canep.2026.103016. Online ahead of print.
ABSTRACT
BACKGROUND: The target trial emulation (TTE) framework, proposed by Hernán and Robins, uses observational data to emulate a randomized controlled trial (RCT). TTEs are increasingly being applied in oncology research. This scoping review aims to describe the characteristics of oncology TTEs, evaluate their adherence to the TTE framework, and assess the concordance of results between TTEs and corresponding RCTs.
METHODS: A comprehensive search was conducted in MEDLINE and Embase from inception to December 25th 2025. Only oncology TTEs evaluating treatment interventions were eligible. Data was extracted on study characteristics, adherence to the TTE framework, reported cohort characteristics, the concordance of TTEs emulating specific RCTs using Cohen’s Kappa coefficient, and the correlation of Ln hazard ratio (HR) using Pearson’s correlation coefficient.
RESULTS: A total of 94 studies were identified, representing 106 unique TTEs. All TTEs reported on the treatment strategies, outcomes measured, and data analysis plan, while only 75.5 % presented a clearly defined time zero. In addition, only 20.8 % of TTEs reported on patient performance status, for the purpose of adjusting confounders. Additionally, among the 20 TTEs that explicitly emulated a published RCT, there was poor to fair concordance (Cohen’s Kappa = 0.20) between the reported results of the statistical hypothesis testing of survival outcomes between the respective TTE and corresponding RCT. The Pearson’s correlation coefficient between Ln HRs of TTE and RCT was 0.44.
CONCLUSION: The TTE framework adoption and adherence in oncology has been substantial. However, the poor to fair agreement between corresponding TTEs and RCTs demonstrates the potential caveats of using TTEs as a replacement for RCTs in the evaluation of treatment efficacy, notwithstanding atypical scenarios where RCTS may not be feasible. One potential source of residual bias may be the lack of adjustments based on patient performance status. Significant gaps in reporting of critical oncology endpoints pose further challenges. Future research should continue to standardize reporting guidelines, specifically aligning with the recently published TARGET framework, to improve the utilization of TTEs in oncology.
PMID:41762536 | DOI:10.1016/j.canep.2026.103016
