接受血液系统恶性肿瘤治疗的患者报告躯体功能的纵向图表

The US Food and Drug Administration (FDA) released a draft guidance document detailing core patient-reported outcomes in cancer clinical trials, including physical function (PF). The objectives of this study were to develop analytic methods and visualizations of patient-reported PF in patients with cancer.

We applied an estimand framework to a patient-reported tolerability endpoint to develop data summaries cross-sectionally and over time, along with visualizations. We accomplished this through iterative feedback with clinicians, statisticians, and FDA stakeholders using three clinical trial datasets in hematologic malignancies. Graphical approaches were applied to three datasets in hematologic malignancies: (1) patients with myeloproliferative neoplasms enrolled in MPN-RC 111/112 trials completed EORTC QLQ-C30 over 12 months; (2) patients with hematologic malignancies undergoing CAR-T cell therapy or autologous transplant who completed FACT questionnaires over 6 months; and (3) patients with multiple myeloma or amyloidosis who completed the PROMIS-29 questionnaire over 6 months. Zoom polls were administered to two stakeholder groups (clinicians/clinical investigators and patient advocates) to elicit feedback.

Visualizations included stacked bar charts, line plots of arithmetic mean changes from baseline, pie charts, waffle plots, and waterfall plots of PF data. Graphics considered scaled scores and individual items and included delineation of PRO completion rate at each time point. Confidence intervals and reference lines were included as applicable, and colorblind accessible colors were implemented to ensure inclusivity of all visualizations. Data summaries over time reporting "worst" change were difficult to interpret. In terms of stakeholders' preference, patients preferred stacked bar charts while clinicians equally favored stacked bar charts and line plots; both patients and clinicians preferred waterfall plots to pie charts. Patient feedback highlighted the need for various graphics to convey group level trends and granular individual-patient level information.

Patient-reported PF informs the evaluation of treatment tolerability in cancer trials. Data summaries and visualizations of physical function developed through an iterative process were reviewed favorably by patients, clinicians and FDA stakeholders in this study. Future work to systematically assess accuracy of interpretation of the various analytic and visualization methods is a necessary next step across clinical, regulatory, payer and patient stakeholders. TRIAL REGISTRATION: NCT01259817, NCT01259856.