Abstract
AbstractWe developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92–0.94) and the Lung Cancer Symptom Scale-Mesothelioma (0.79–0.87) at each co-administration of the scales. The CSS also had good sensitivity to worsening disease and global quality-of-life ratings. The MDASI-MPM CSS can be used as an outcome in MPM clinical trials, including in responder analyses and at the individual patient level. It is brief enough to administer frequently, including electronically, to better capture symptom trajectories during and after a trial and in clinical practice. As a single score, the CSS addresses multiplicity issues that can arise when several symptoms increase due to worsening disease. Our process can be adapted to produce a CSS for other advanced-cancer trials.
Funder
Bayer HealthCare Pharmaceuticals
National Institutes of Health
Publisher
Springer Science and Business Media LLC
Reference39 articles.
1. Kluetz, P. G. et al. Focusing on core patient-reported outcomes in cancer clinical trials: Symptomatic adverse events, physical function, and disease-related symptoms. Clin. Cancer. Res. 22, 1553–1558. https://doi.org/10.1158/1078-0432.CCR-15-2035 (2016).
2. Cleeland, C. S. et al. The symptom burden of cancer: Evidence for a core set of cancer-related and treatment-related symptoms from the Eastern Cooperative Oncology Group Symptom Outcomes and Practice Patterns study. Cancer. 119, 4333–4340. https://doi.org/10.1002/cncr.28376 (2013).
3. US Food and Drug Administration. Guidance for industry. Patient-reported outcome measures: use in medical product development to support labeling claims (2009). https://www.fda.gov/media/77832/download.
4. US Food and Drug Administration. Core patient-reported outcomes in cancer clinical trials. Guidance for industry (draft). (2021). https://www.fda.gov/media/149994/download.
5. US Food and Drug Administration. Patient-focused drug development: Collecting comprehensive and representative input. Guidance for industry, Food and Drug Administration staff, and other stakeholders (2018). https://www.fda.gov/media/139088/download.