Clinical trial and real-world data: A comparative study in patients with diabetic kidney disease

Objective A growing body of research is focusing on clinical real-world data (RWD) to supplement or replace randomized controlled trials (RCTs). However, due to the disparities in data generation mechanisms between RCTs and RWDs, differences are likely and necessitate scrutiny to validate the merging of these datasets. Materials and Methods We compared the temporal and completeness characteristics of pharmaceutical RCT data from 5,734 diabetic kidney disease patients with corresponding RWD from electronic health records (EHRs) of 23,523 patients. Demographics, diagnoses, medications, laboratory measurements, and vital signs were analyzed using visualization, descriptive statistics, statistical testing, and cluster analysis. Results RCT and RWD sets exhibited significant differences in prevalence, longitudinality, completeness, and sampling density. The cluster analysis revealed distinct patient subgroups within both RCT and RWD sets, as well as clusters containing patients from both sets. Discussion and Conclusions The results highlight the differences between RCT and RWD datasets, and their respective data generation mechanisms. Nonetheless, in certain instances, RWD has the potential to enrich RCT data. These discrepancies should be taken into account during the planning stages of an RCT-RWD study, and we stress the importance of validation to verify the feasibility of combining RCT and RWD. Moreover, advanced methods are needed to mitigate these differences, for instance, when building an external control arm. ### Competing Interest Statement Samu Kurki and Jussi Leinonen are employed by Bayer Oy (Finland). ### Funding Statement This study was funded by Bayer Oy (Finland). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of HUS Helsinki University Hospital, Finland, gave ethical approval for this work, retrospective registry study permit HUS/230/2022. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Regarding the RWD, according to the Finnish legislation, access to individual-level data is restricted only to individuals named in the study permit. The study protocol is available upon request from the corresponding author. Regarding the RCT data, the data are not publicly available due to containing information that could compromise research participant privacy/consent.