Benefits and public interests

This research has a great potential in extrapolating outcomes from Randomised Controlled Trials (RCTs).

RCTs have long been considered as the ‘gold standard’ to inform clinical guidelines. However, they have significant limitations in external validity. The trial outcomes and conclusions are only directly applicable to the subjects involved in the studies, who might not be representative to the entire real-world population. Many individuals with vulnerable characteristics in the real-world are not well represented in RCTs. Consequently, this leaves a significant knowledge gap with no answers to many important clinical questions.

Answers to many key clinical questions about people with multimorbidity and other perceived vulnerabilities can be found in real-world data that are routinely collected in clinical practices. Typically observational studies are involved to study the real world data. However, contributions of the existing observational studies are hindered by many key barriers and bias within the data. Observational studies have inherent limitations in their ability to identify treatment effects due to their observational nature.

The virtual trial emulation is an innovative evidence-based approach to extrapolate RCT outcomes using real-world data. They are interventional and support counterfactual emulations. Health professionals will be able to run emulations on their target population, examine the outcomes of the emulations and make a judgement on whether the effect sizes calculated from the emulations provide right answers about their clinical questions.

The emulated trials offer high quality synthetic data that preserve the same value for research as the real datal. Compared with anonymised real data, synthetic data can address their main caveats including bias, data imbalance, noise and missing measurements. They are also in a much better position to overcome legal barriers in data protection and sharing.

Overall, the virtual trial emulations offer a time /cost saving, and privacy-preserving solution to extrapolate RCT outcomes and a new way to provide real-world evidence to address target clinical questions which would otherwise be impossible to address in RCTs. This will open doors to a landscape change to revolutionise future biomedical and health research. Research in this direction will speed up timelines for clinical knowledge discovery, address complex problems in elderly population and multi-morbidity, and potentially transform regulatory and policy making process.