Preliminary Attainability Assessment of Real-World Data for Answering Major Clinical Research Questions in Breast Cancer Brain Metastasis: Framework Development and Validation Study

Abstract

Background: In recent decades, real-world evidence (RWE) in oncology has rapidly gained traction for its potential to answer clinical questions that cannot be directly addressed by randomized clinical trials. Integrating real-world data (RWD) into clinical research promises to contribute to more sustainable research designs, including extension, augmentation, enrichment, and pragmatic designs. Nevertheless, clinical research using RWD is still limited because of concerns regarding the shortage of best practices for extracting, harmonizing, and analyzing RWD. In particular, pragmatic screening methods to determine whether the content of a data source is sufficient to answer the research questions before conducting the research with RWD have not yet been established.

Objective: We examined the PAR (Preliminary Attainability Assessment of Real-World Data) framework and assessed its utility in breast cancer brain metastasis (BCBM), which has an unmet medical need for data attainability screening at the preliminary step of observational studies that use RWD.

Methods: The PAR framework was proposed to assess data attainability from a particular data source during the early research process. The PAR framework has four sequential stages, starting with clinical question clarification: (1) operational definition of variables, (2) data matching (structural/semantic), (3) data screening and extraction, and (4) data attainability diagramming. We identified 5 clinical questions to be used for PAR framework evaluation through interviews and validated them with a survey of breast cancer experts. We used the Samsung Medical Center Breast Cancer Registry, a hospital-based real-time registry implemented in March 2021, leveraging the institution's anonymized and deidentified clinical data warehouse platform. The number of breast cancer patients in the registry was 45,129; it covered the period from June 1995 to December 2021. The registry consists of 24 base data marts that represent disease-specific breast cancer characteristics and care pathways. The outcomes included screening results of the clinical questions via the PAR framework and a procedural diagram of data attainability for each research question.

Results: Data attainability was tested for study feasibility according to the PAR framework with 5 clinical questions for BCBM. We obtained data sets that were sufficient to conduct studies with 4 of 5 clinical questions. The research questions stratified into 3 types when we developed data fields for clearly defined research variables. In the first, only 1 question could be answered using direct data variables. In the second, the other 3 questions required surrogate definitions that combined data variables. In the third, the question turned out to be not feasible for conducting further analysis.

Conclusions: The adoption of the PAR framework was associated with more efficient preliminary clinical research using RWD from BCBM. Furthermore, this framework helped accelerate RWE generation through clinical research by enhancing transparency and reproducibility and lowering the entry barrier for clinical researchers.

Keywords: PAR framework; brain metastasis; breast cancer; clinical data warehouse; observational study; preliminary attainability assessment; real-world data.

Figure 1

Illustration of the Preliminary Attainability Assessment of Real-World Data (PAR) framework and study design. CQ: clinical question.

Figure 2

Results at stages 1 and 2 with the breast cancer brain metastasis clinical questions. CQ: clinical question.

Figure 3

Data attainability for the clinical questions. Clinical questions were as follows. (A) Is there a difference in survival outcomes between the brain as the primary metastasis site and brain metastasis accompanied by systemic metastasis? (B) Does systemic treatment for brain metastasis patients affect survival outcomes according to subtype? (C) Does the timing of systemic treatment initiation affect survival outcomes when brain metastasis is accompanied by systemic metastasis? and (D) Is there a difference in the prediction of brain metastasis in patients who previously received trastuzumab alone for neoadjuvant therapy and in patients who received pertuzumab and trastuzumab for neoadjuvant therapy? BCBM: breast cancer brain metastasis; HER2: human epidermal growth factor receptor 2; HR: hormone receptor; TNBC: triple-negative breast cancer.

Figure 4

Preliminary Attainability Assessment of Real-World Data framework evaluation in stages 1 to 4. CQ: clinical question; CDW: clinical data warehouse.