From Trial Eligibility to Real-World Evidence

Whether findings observed in trial-like populations remain consistent in broader real-world populations?

Real-world data begins as a connected as a connected ecosystem

Modern healthcare data rarely exist in a single table.

Patients, diagnoses, medications and healthcare encounters must be integrated into a patient-level analytical dataset before meaningful scientific questions can be addressed.

Real-world evidence begins with data integration rather than statistical modeling.




Trial eligibility dramatically resphaes populations

Applying realistic eligibility criteria to a synthetic population of 20,000 patients progressively reduced the cohort to 1,924 trial-eligible individuals.

Trial populations are not merely smaller populations; they are systematically different populations created through selection.



Trial-like patients are different patients

Compared with the broader population, trial-like patients had lower healthcare utilization, lower comorbidity burden and fewer exclusionary conditions.

Eligibility criteria change the clinical profile of the population under study.




Prediabetes predicts future diabetes

  • Hypertension only: 12.5%

  • Hypertension + Prediabetes: 15.7%

This corresponds to an absolute difference of 3.2 percentage points and an approximately 26% relative increase in risk.
Baseline prediabetes identifies a subgroup at elevated future diabetes risk.

Relative effects can be stable accross population

  • Full cohort: OR = 1.32, p = 0.004

  • Trial-like cohort: OR = 1.69, p = 0.406

  • RWE-only cohort: OR = 1.23, p = 0.036


Although statistical significance was lost in the smaller trial-like cohort, the direction of association remained consistent.

Differences between trial and RWE populations may affect precision more than effect direction.





Testing transportability directly


  • Interaction p-value = 0.622

No evidence was found that the relationship differed between populations.

The association appeared transportable across populations despite substantial differences in baseline risk.


Conclusion

Real-world evidence does not replace randomized clinical trials. Instead, it provides a framework for understanding how far trial-derived findings can travel once they leave the controlled environment in which they were generated.
In this synthetic healthcare population, trial eligibility substantially altered patient selection, but the prognostic importance of prediabetes remained remarkably consistent across trial-like and real-world settings.