Document Type

Dissertation

Date of Degree

6-10-2025

Primary Advisor

Mary Corcoran

Abstract

Background

High-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are aggressive hematologic malignancies with poor prognoses, where extending survival often comes at the cost of substantial morbidity. This study was grounded in the quality of survival (QoS) framework, which emphasizes that treatment outcomes should balance longevity with the health-related quality of life (HRQoL) experienced during the period of survival. In this context, patient-reported outcomes are crucial to capturing what truly matters to patients. However, existing patient-reported outcome measures (PROMs) used in MDS/AML clinical trials may not fully reflect patient priorities. A complementary Wilson–Cleary model perspective, linking biological factors to patient-perceived outcomes, was applied to ensure the full spectrum of patient experience, from symptoms to overall quality of life (QoL), is considered. There is a clear need to evaluate whether current PROMs adequately cover the domains of HRQoL most salient to high-risk MDS and AML patients and to identify gaps where important patient-centered domains might be underrepresented.

Study Objectives

The aim of this dissertation was to measure what matters to patients by: (a) eliciting and characterizing the key domains of HRQoL as described by patients with high-risk MDS/AML, thereby developing a patient-informed conceptual model of HRQoL in this population; and (b) evaluating the content validity of existing PROMs against this conceptual model. The ultimate objective was to determine whether current instruments capture the patient-identified domains (and to pinpoint any discrepancies) to inform the selection or development of more appropriate outcome measures for future trials and care improvement. These objectives were pursued within a theoretical foundation that integrates the QoS framework with patient-centered outcomes research principles, supplemented by the Wilson–Cleary model to interpret findings in a broader outcomes continuum.

Methods

A mixed-methods interpretive descriptive design was employed. Seventeen patients with higher-risk MDS or secondary AML (median age 65) participated in in-depth semistructured concept elicitation interviews to explore their experiences, symptoms, values, and treatment goals. The qualitative methodology employed was interpretive description, which enabled inductive thematic analysis of interview transcripts to capture complex clinical and psychosocial phenomena in patients’ own terms. This approach was complemented by a quantitative survey, in which participants ranked or rated the importance of various HRQoL concerns and outcomes. The survey served to validate and prioritize the domains that emerged from the interviews. Using a content analysis approach, the patient-derived domains were then systematically compared to the content of commonly used PROMs in MDS/AML (identified through literature and clinical trial usage) to assess content validity. Specifically, the study focused on which patient-prioritized domains each instrument covered and where gaps existed. To interpret the relationships among domains and their impact, the Wilson–Cleary HRQoL model was used to map each domain to levels (from symptoms to overall quality of life), and the alignment with the QoS framework was assessed. This multi-method approach ensured triangulation—qualitative insights defined the conceptual model, whereas quantitative data and comparative analysis with existing measures provided validation and context.

Results

Thematic analysis revealed seven core domains of HRQoL that patients living with high-risk MDS/AML consistently emphasized: (a) Physical Symptom Burden (dominated by fatigue, pain, and other distressing symptoms); (b) Functional Independence (Autonomy) in daily life (ability to maintain self-care and usual activities without undue reliance on others); (c) Emotional Well-Being (psychological distress, anxiety about the future, and coping with uncertainty); (d) Social Well-Being (support from family/friends and the impact of isolation), (e) Healthcare Experience and Treatment Satisfaction (quality of communication with providers, trust in the care team, and satisfaction with treatment and symptom management), (f) Personal Values and Goals (individual priorities such as life milestones, survival vs. quality trade-offs, and alignment of care with what patients value), and (g) Cognitive/Informational aspects (mental clarity and being informed/knowledgeable about one’s condition and care—a domain intertwined with feeling in control). These patient-informed domains collectively form a new conceptual model of HRQoL for high-risk MDS/AML, reflecting a holistic patient perspective. In the quantitative surveys, patients’ rankings corroborated the qualitative findings—domains such as treatment satisfaction, trust in the medical team, autonomy, and fatigue were rated among the most important aspects affecting their quality of life. Notably, maintaining a sense of control (autonomy in decision-making and daily activities) and having confidence in the treatment plan emerged as top priorities, alongside the management of physical symptoms and emotional health. Content Validity Assessment: When comparing the seven patient-identified domains to the content of existing PROMs (including general cancer HRQoL questionnaires and hematology-specific instruments), substantial gaps were found in coverage. Most existing measures thoroughly capture physical symptoms (e.g., fatigue levels) and general emotional distress. However, none of the reviewed PROMs fully covered certain domains that the patients deemed critical. In particular, Autonomy (independence and control) and Treatment Satisfaction/Healthcare Experience were largely absent from standard HRQoL instruments. These aspects—how satisfied patients are with their treatment process and outcomes, and the extent to which they can preserve independence—are currently assessed, if at all, only through separate measures or ad hoc questions, not within core HRQoL PROMs. Furthermore, patient-centered priorities and personal values, such as goal alignment or trade-off preferences, were only indirectly or sparsely represented in existing instruments. For example, although social functioning scales capture interactions, they may not address the deeper impact of being a burden or the importance of role fulfillment that patients highlighted. Similarly, generic measures lack items on patients’ evaluation of care (e.g., feeling heard by providers or confident in the care plan), which the current study revealed as integral to their quality of life. This content-mapping analysis indicates that current PROMs used in MDS/AML trials provide an incomplete picture of patient well-being, covering many clinical symptoms and general domains but missing the nuanced domains of autonomy, treatment experience, and individualized priorities that emerged as salient in this population.

Findings

Integrating the qualitative and quantitative results, the patient-informed conceptual model offers a comprehensive view of HRQoL in high-risk MDS and AML, extending the traditional domains to include what patients value most in their disease journey. Mapping these domains onto the Wilson–Cleary model demonstrated that patient concerns span the continuum from biological impairments (e.g., cytopenias causing fatigue) to symptoms and functional limitations (e.g., loss of independence), through general health perceptions (e.g., emotional well-being and satisfaction with care), ultimately impacting the apex—overall quality of life. The findings underscore that for these patients, quality of survival is defined by more than clinical response or length of life—it is fundamentally influenced by psychosocial factors (i.e., emotional health and social support), personal agency (i.e., autonomy in life and treatment), and the quality of the treatment experience. These domains align with the QoS framework’s assertion that both the quantity and quality of life must be considered in assessing outcomes. Notably, the critical domains of autonomy, treatment satisfaction, and alignment with personal goals emerged as decisive to patients’ overall QoL, yet they are not captured by commonly used instruments. This misalignment suggests that current clinical trials and practice may overlook key indicators of patient benefit. In conclusion, the study provides evidence that existing PROMs in hematologic malignancies should be reexamined and possibly enhanced to ensure content validity for high-risk MDS/AML populations. The seven-domain patient-derived model can guide the refinement of outcome measures or the development of a new disease-specific PROM that includes domains such as patient autonomy, treatment experience, and individualized priorities alongside traditional HRQoL facets. By incorporating these patient-identified domains, researchers and clinicians can better measure meaningful outcomes—truly “what matters to patients”—thereby improving patient-centered care and the evaluation of new therapies in these life-threatening conditions. The theoretical lens of the QoS framework, complemented by the Wilson–Cleary model, reinforces that improving overall quality of survival for MDS/AML patients will require addressing not only disease control but also the humanistic domains that define the lived experience of this illness.

Comments

©2025 by Anthony J. Messina. All rights reserved

Open Access

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