Generating real-world tumor burden endpoints from electronic health record data: Comparison of RECIST, radiology-anchored, and clinician-anchored approaches for abstracting real-world progression in non-small cell lung cancer

Abstract

Real-world evidence derived from electronic health records (EHRs) is increasingly recognized as a supplement to evidence generated from traditional clinical trials. In oncology, tumor-based Response Evaluation Criteria in Solid Tumors (RECIST) endpoints are collected in clinical trials. The best approach for collecting similar endpoints from EHRs remains unknown.We evaluated the feasibility of a traditional RECIST-based methodology to assess EHR-derived real-world progression (rwP) and explored non-RECIST-based approaches. In this retrospective study, cohorts were randomly selected from Flatiron Health's database of patient-level EHR data in advanced non-small cell lung cancer. A RECIST-based approach was tested for feasibility (N=26). Three non-RECIST abstraction approaches were tested for feasibility, reliability, and validity (N=200): (1) radiology-anchored, (2) clinician-anchored, and (3) combined.RECIST-based cancer progression could be ascertained from the EHRs of 23% of patients (6/26).In 87% of patients (173/200), at least one rwP event was identified using both the radiologyand clinician-anchored approaches. rwP dates matched 90% of the time. In 72% of patients (124/173), the first clinician-anchored rwP event was accompanied by a downstream event (e.g., treatment change); the association was slightly lower for the radiology-anchored approach (67%; 121/180). Median overall survival (OS) was 17 months (95% confidence interval [CI]: 14, 19). Median real-world progression-free survival (rwPFS) was 5.5 (95% CI: 4.6, 6.3) and 4.9 months (95% CI: 4.2, 5.6) for clinician-anchored and radiology-anchored approaches, respectively. Correlations between rwPFS and OS were similar across approaches (Spearman's rho: 0.65-0.66). Abstractors preferred the clinician-anchored approach as it provided more

STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world

“…Real-world progression was determined by physician assessment as described previously [ 37 ]; the date and type of progression (actual progression [based on radiographic evidence, pathologic evidence, or clinical assessment], pseudo-progression, or mixed progression) were recorded in the Flatiron database and comprised variables within the dataset. PFS was defined as the time until the earliest record of actual disease progression or death from any cause from initiation of line of therapy (first- or second-line).…”

Beyond Randomized Clinical Trials: Use of External Controls

“…The progression variable is extracted from RWD collected in the EHR as part of routine clinical care, and the information about each progression event is retrospectively captured. 53 This is conceptually different than prospective collection of progression data within the context of a clinical trial. Hence, each documented progression event in the Flatiron/FMI CGDB is labeled realworld progression (rwP).…”

Real‐world progression, treatment, and survival outcomes during rapid adoption of immunotherapy for advanced non–small cell lung cancer

“…Analyzing those sources to create real‐world evidence, however, necessitates specific approaches for abstracting endpoints (ie, real‐world PFS [rwPFS]), accounting for differences between clinical trials and real‐world practice and documentation patterns. For example, descriptions of progression on imaging reports may bypass Response Evaluation Criteria in Solid Tumors (RECIST) language. Contemporary and robust real‐world evidence is crucial for helping clinicians tailor new treatments, such as immunotherapy, to real‐world patients with advNSCLC.…”