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. 2025 Apr 15;6(4):102081. doi: 10.1016/j.xcrm.2025.102081

Table 1.

Comparison between cohort studies and target trial emulation

Cohort study Target trial emulation Random controlled trials
Characteristics

Study type observational both experimental
Sample Size large either small
Representativeness high medium low
Confounding factors more some less
Follow-up time long either short
Dias risks high medium low
Evidence quality low medium high
To real world near near far
Statistical analysis Cox proportional-hazards model or mixed models flexible, G methods, standard methods for observational data
Strengths reliable causality
wide applications
multiple outcome analysis
cost-efficiency
reduce self-inflicted biases
informative to patient care: by describing the target trial population, treatment strategies, follow-up time, and outcome, investigators clarify when and how their results might be informative to patient care
Limitations time-consuming and costly
loss to follow-up
control confounding factors
lack of randomization: observational data inherently lack randomization, requiring an assumption that treatment strategies can be compared as if they were randomized
restriction to pragmatic trials: certain features of highly controlled trials (e.g., blinded treatment assignment) cannot be replicated using observational data
inability to study novel treatments: investigators can only consider treatment strategies used in practice and captured in observational data
Key points clear temporal sequence and etiological exploration explicitly defined target trial protocol (time zero)