Comparison of Population Characteristics in Real-World Clinical Oncology Databases in the US: Flatiron Health-Foundation Medicine Clinico-Genomic Databases, Flatiron Health Research Databases, and the National Cancer Institute SEER Population-Based Cancer Registry

Background The Flatiron Health-Foundation Medicine Clinico-Genomic Databases (CGDBs) are de-identified, real-world data sources that link comprehensive genomic profiling (CGP) data with clinical data derived from electronic health records (EHRs) for patients with cancer. Comparing the CGDBs to the US population of patients with cancer allows researchers to understand the representativeness of a cohort when designing, conducting, and interpreting their analyses. The objective of this study was to compare the demographic and clinical characteristics of patients in the CGDBs with the Flatiron Health Research Databases (FHRDs) and The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) population-based cancer registry. Methods We compared disease-specific CGDBs that had corresponding disease-specific FHRDs with relevant SEER patients using demographic and clinical characteristics of patients with cancer who had documented care from January 1, 2011 to March 31, 2021. For CGDBs where a corresponding disease-specific FHRD does not exist, comparisons were only done against SEER. The SEER Incidence Data 1975-2018 Research Database was used for this analysis, of which patients with a relevant cancer diagnosis from January 1, 2011 to December 31, 2018 were included. Subgroup analyses were performed to address potential biases related to temporal drifts and allow for a more direct comparison of the datasets as well as to examine biases that may be due to data missingness. The impact of the determination to reimburse for next generation sequencing (NGS) testing was not feasible to analyze given the most recent SEER data was available only through the end of 2018 at the time this study was conducted. Results The overall distribution of cancer types was similar between the 22 CGDB databases and SEER. The overall distributions of gender and diagnosis year were similar across all databases. The CGDB has a lower proportion of patients who were aged 80 years or older at initial diagnosis compared to FHRD and SEER cohorts. However, narrower differences were observed in diseases where targeted therapies are approved and comprehensive genomic profiling is indicated (e.g., Melanoma, NSCLC). The proportion of incomplete records for race in the CGDB and FHRD was greater than in SEER. Completeness of stage varied by disease across all 3 cohorts, but was generally lower in CGDB and FHRD for clinical and data model design reasons. Overall the stage distributions for solid tumor cohorts were similar across CGDB and FHRD with SEER tending to have more earlier stage patients, which is expected given differences in data collection methods for the sources. Conclusion This comparative analysis of real-world, US-based oncology databases provides crucial insights into the similarities and differences in patient characteristics across these three types of data sources. Observed variances could be due to several factors, including differences in CGP testing dynamics and data collection approaches used to create each of the databases. Ongoing monitoring and evaluation of the representativeness of these databases will be critical to help researchers and regulators contextualize evidence from the CGDBs, particularly as the CGDBs are expected to change over time due to increased adoption of CGP as part of routine clinical practice for a growing number of cancers. ### Competing Interest Statement TS, JS, and CCP report employment at Flatiron Health, Inc., which is an independent subsidiary of the Roche Group, as well as stock ownership in Roche. TS and JS also report equity ownership in Flatiron Health, Inc. VF and LC report employment at Foundation Medicine, Inc., which is an independent subsidiary of the Roche Group, and stock ownership in Roche. MM reports former employment at Flatiron Health and current employment at GRAIL, Inc. MM also holds shares in Roche, GRAIL, and Illumina. SS reports former employment at FMI as well as stock ownership in Pfizer, Roche and EQRx. ### Funding Statement This study was sponsored by Flatiron Health, Inc. and Foundation Medicine Inc., which are independent subsidiaries of the Roche group. ### 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: Institutional Review Board approval of the study protocol was obtained prior to study conduct, and included a waiver of informed consent by WCG IRB. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study have been originated by Flatiron Health, Inc. Requests for data sharing by license or by permission for the specific purpose of replicating results in this manuscript can be submitted to dataaccess{at}flatiron.com