Imagine a future where the data generated in clinical trials doesn’t vanish at study closeout but continues to yield insights for years. Picture clinical evidence that integrates real-world outcomes, slashing data collection costs while boosting trial power and relevance. A scoping review shows how linking clinical trials to real-world data (RWD) can increase the reliability of the clinical research data.
This comprehensive scoping review, published in JAMA Network Open this month, explores the landscape of clinical trials linked to routinely collected data, such as electronic health records (EHRs), insurance claims, registries, and vital statistics, between 2016 and 2023. With 71 qualifying studies across diverse countries and therapeutic areas, the review illustrates how linking trial data to real-world data enhances clinical research with minimal burden and maximal insight.
Clinical trials remain the gold standard for establishing treatment efficacy, but they are often constrained by high costs, short follow-ups, and limited generalizability. Meanwhile, trial participants continue to interact with the healthcare system, generating rich streams of passive data. Linking these real-world datasets to trial participants—when done responsibly—can extend follow-up, validate outcomes, monitor safety, assess costs, and even inform health technology assessments (HTAs) and coverage decisions.
Among 71 studies identified, linkage was achievable across varied settings. Roughly 60% of trials investigated drugs, vaccines, or supplements, while 40% focused on devices or procedures. Most trials were late-stage (phase III or IV), especially for pharmaceuticals, showing the maturity and real-world relevance of the linkage model. The top four applications of linkage were:
- Posttrial long-term follow-up (31%) – Extending observation beyond the original trial.
- Capturing trial outcomes (27%) – Supplementing or replacing primary/secondary endpoints.
- Validating outcomes (24%) – Cross-checking RWD against trial-adjudicated data.
- Resource utilization & cost analysis (17%) – Informing economic models for payers and HTAs.
Claims data dominated (58%), followed by EHR/lab data (24%) and registries/vital stats (18%). Deterministic linkage using unique identifiers (e.g., NHS or Medicare numbers) was the standard; probabilistic methods were rare but used when identifiers were absent. In nearly half of the studies, consent for data linkage was proactively obtained during the trial. Another 47% operated under a waiver granted by ethical boards, suggesting that linkage is ethically permissible under proper governance.
Cardiovascular (42%) and oncology (25%) trials led the way in linkage adoption, showing high potential in fields with chronic and costly outcomes. The U.S. and U.K. accounted for the majority of trials, but linkage practices were found across Europe, Canada, Australia, and even Asia. This global spread indicates a rising international consensus on the value of RWD-enhanced trials.
This is more than a trend, it’s a paradigm shift. Linking trials to real-world data isn’t just feasible, it’s transformative. It supercharges traditional trials with scale, continuity, and relevance while cutting costs and reducing patient burden. Regulators, payers, and researchers alike should think outside the box to go beyond siloed clinical data. The next generation of evidence is integrated, longitudinal, and real-world smart. If you’re running or designing trials, start planning for RWD linkage now. It’s not just innovative, it’s essential.
