Assessing Patient-Reported Outcomes in People with Myelodysplastic Syndromes: Can a Customized Selection of Items from the EORTC Library Enhance the EORTC QLQ-C30?
Authors: Bell Jill A , Pompilus Farrah A , Christian Anna , Mazerolle Flora , Scipione Fatima , Bejar Rafael , Galaznik Aaron , Fram Robert J. , Faller Douglas V. , Cano Stefan , Regnault Antoine 
Published: October 2019

Abstract
INTRODUCTION
Assessing patient-reported outcomes (PROs) is an essential part of understanding the ways in which a new drug might affect how a patient with cancer feels and functions within a clinical trial. Certain widely used PRO measures are now being supplemented with a selection of items from available item banks to ensure the measure is targeted to the specific context of use. Previous mixed methods research in higher risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML), and low blast acute myeloid leukemia (LB AML) led to the development of a conceptual model of the symptoms and impacts for this population. It informed a PRO measurement strategy based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) along with an additional, customized selection of 10 supplemental items from the EORTC library to cover unaddressed concepts. Clinical features such as anemia cause fatigue and dyspnea, which may negatively impact patient functioning, thus further emphasizing the importance of the patient voice when evaluating the value of a new therapy to patients. The purpose of this research was to incorporate the patient voice and generate information on this measurement strategy in a sample of people with HR MDS/ CMML and LB AML.
METHODS
This study was a one-time, cross-sectional patient-reported survey administered online. People living with HR MDS, non-proliferative CMML, and LB AML were recruited through the MDS Foundation, social media, and recruitment agencies. Patients completed the EORTC QLQ-C30 plus 10 supplemental items from the EORTC item library. In addition to PRO data, they were also asked to record demographics and disease-related information. Responses to the 40 PRO items were described and psychometric analyses based on Rasch measurement theory (RMT) were conducted on the original multi-item domains of the EORTC QLQ-C30. RMT analysis defines how a set of items should perform to generate reliable and valid measurements, which is important for the generalizability of the PRO instrument's psychometric evaluations to other contexts of use. RMT analyses were also performed on the following, enhanced domain measures which included original items and supplemental items: fatigue, dyspnea, physical functioning, and role functioning.
RESULTS
A total of 51 patients were recruited and participated in the online survey (HR MDS: 51%; CMML: 27%; LB AML: 10%). The mean age was 67.2 (SD: 11.8) and 49% of patients were female. The description of responses showed a possible floor effect for several EORTC QLQ-C30 items (i.e. a substantial percentage of responder reported the lowest value of the scale), whereas the responses to the supplemental items were well distributed across the response categories (Figure). This confirmed that the customized supplemental item selection was well targeted to the patient sample. Overall, the RMT psychometric examination of the original EORTC QLQ-C30 domain scores showed satisfactory ability to assess key outcomes for people with HR MDS/CMML and LB AML including fatigue and physical functioning. However, it highlighted some areas for possible improvement, due to gaps in the conceptual coverage of symptoms and impacts of HR MDS/CMML and LB AML. The enhanced fatigue, physical functioning and dyspnea measures that combined the original QLQ-C30 items with the supplemental items from the EORTC library showed improved measurement performances for these key domains for people with HR MDS/CMML and LB AML, typically in terms of conceptual coverage.
CONCLUSIONS
Our data shows how incorporating the patient voice early on in PRO measurement selection and a conceptually-driven approach to the development of customized item sets can lead to more fit-for-purpose PRO measures to be used in the context of clinical trials of patients with cancer. Specifically, while the QLQ-C30 may be a satisfactory PRO instrument for use in people with hematological stem cell disorders, it can be made more targeted and disease-specific by carefully utilizing mixed methods and selecting supplemental items from the EORTC item library. This patient-reported online survey provides early evidence, in a small sample of patients, on the appropriateness of both the original QLQ-C30 and enhanced item sets to assess PROs in HR MDS/CMML, and AML and should be further analyzed in future research.

Disclosures
Bell: Takeda Pharmaceuticals: Employment, Equity Ownership. Pompilus:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Christian:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Mazerolle:Modus Outcomes: Employment; Takeda Pharmaceuticals: Research Funding. Scipione:Takeda Pharmaceuticals: Employment. Bejar:Takeda: Research Funding; Celgene: Consultancy, Honoraria; Foundation Medicine: Consultancy; Modus Outcomes: Consultancy; Genoptix: Consultancy; AbbVie/Genentech: Consultancy, Honoraria; Astex/Otsuka: Consultancy, Honoraria. Galaznik:Takeda Pharmaceuticals International Co.: Employment. Fram:Takeda Pharmaceuticals: Consultancy; BeyondSpring Pharmaceuticals, Inc.: Consultancy. Faller:Takeda Pharmaceuticals: Employment, Equity Ownership. Cano:Modus Outcomes: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Research Funding. Regnault:Modus Outcomes: Employment, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Research Funding.