Linkage of Clinical Trial Data to Routinely Collected Data Sources: A Scoping Review

Patients who participate in clinical trials generate valuable routinely collected data (eg, medical records, electronic health records, claims databases, disease registries, or vital statistics) through their routine interactions with the health care system before, during, and after the trial. When this routinely collected data is linked at the participant level, it can supplement active data collection in the trial and provide deeper insights into the benefits, risks, and costs of treatments.

To review clinical trials linked to routinely collected data in various countries, identifying the use cases and designs of these linkage studies.

Research articles that reported the linkage of clinical trials to medical records, electronic health records, claims databases, disease registries, or vital statistics in their title or abstract were searched for in PubMed and MEDLINE. The search covered the period from January 1, 2016, through December 30, 2023. Opinion pieces, study protocols, or studies that involved interventions other than medications, dietary supplements, vaccines, devices, procedures, or diagnostics (eg, behavioral interventions) were excluded. Study eligibility and data extraction were performed independently by 2 reviewers to ensure the accuracy of findings.

Of the 990 abstracts initially screened, a full text review was conducted for 147 articles. In total, 71 studies were included in the results, including 42 medication, vaccine, and dietary supplement trials (59.2%) and 29 device, procedure, or diagnostic trials (40.8%). Of these 71 studies, 24 (32.4%) were conducted in the US. In 32 studies (45.1%), consent for linkage was obtained prospectively as part of the main trial, while 33 studies (46.5%) received a waiver of authorization from the respective ethical review boards. The most frequent use cases of linkage to were posttrial long-term follow-up (22 studies [31.0%]), capturing primary or secondary outcomes of trials (19 studies [26.8%]), validation of routinely collected data outcomes (17 studies [23.9%]), and measuring health care resource utilization and cost in trials (12 studies [16.9%]).

This study found that the linkage of patients' clinical trial data to routinely collected data has been implemented in several trials for various use cases and that most studies obtained consent for linkage prospectively as part of the main trial or received a waiver of authorization from ethical review boards. These findings demonstrate the feasibility and provide an overview of the use cases for linking trials to routinely collected data.