A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia

Jill A Bell; Aaron Galaznik; Farrah Pompilus; Sara Strzok; Rafael Bejar; Fatima Scipione; Robert J Fram; Douglas V Faller; Stefan Cano; Patrick Marquis

doi:10.1186/s41687-019-0123-4

A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia

J Patient Rep Outcomes. 2019 Jun 19;3(1):35. doi: 10.1186/s41687-019-0123-4.

Authors

Affiliations

¹ Millennium Pharmaceuticals, Inc., (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), 40 Landsdowne Street, Cambridge, MA, 02139, USA. jill.bell@takeda.com.
² Millennium Pharmaceuticals, Inc., (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), 40 Landsdowne Street, Cambridge, MA, 02139, USA.
³ Modus Outcomes, Cambridge, MA, USA.
⁴ UC San Diego Moores Cancer Center - MDS Center of Excellence, La Jolla, CA, USA.

Abstract

Background: Novel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use.

Methods: Our mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.

Results: Unique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context.

Conclusion: Supplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning.

Keywords: Acute myeloid leukemia; Chronic myelomonocytic leukemia; Myelodysplastic syndromes; Patient-reported outcomes; Quality of life.