Reliability and validity of EuroQol-5 Dimensions-5 Levels in patients with haematologic malignancies: a cross-sectional study in China.

STRENGTHS AND LIMITATIONS OF THIS STUDY

This cross-sectional study applied the time trade-off method as a reference standard for evaluating the psychometric performance of the EQ-5D instrument across three different haematologic malignancy subtypes.

The study employed multiple statistical approaches, including Cronbach’s α for internal consistency, Spearman’s correlation for criterion validity and exploratory factor analysis for structural validity.

Multivariable linear regression was performed to examine associations between specific clinical characteristics and utility discrepancies between the two measurement methods.

The study was conducted at a single tertiary care centre with a consecutive enrollment of hospitalised patients, which may limit the generalisability of the findings to broader patient populations.

The cross-sectional design of the research prevents the assessment of the instrument’s longitudinal responsiveness to changes in health status or treatment effects over time.

Introduction

Haematologic malignancies, primarily multiple myeloma (MM), leukaemia and lymphoma, are among the most aggressive and debilitating cancers, profoundly impacting patients’ physical, emotional and social well-being. 1 Measuring health-related quality of life (HRQoL) in these patients is essential for understanding disease burden, evaluating therapeutic outcomes and informing patient-centred care decisions. 2 The EuroQol-5 Dimensions-5 Levels (EQ-5D), a widely used generic HRQoL instrument, offers several advantages, including simplicity, adaptability and the ability to generate preference-based utility scores for economic evaluations. 3

Despite the widespread use of EQ-5D in health economic evaluations and clinical research, significant evidence gaps remain regarding its psychometric performance in patients with haematologic malignancies. While some studies have demonstrated moderate-to-high construct validity and responsiveness of EQ-5D in specific subtypes, such as patients with acute leukaemia (AL) unfit for intensive chemotherapy, 4 , 6 the instrument’s performance in other malignancies like MM and lymphoma is less well-established. A recent systematic review catalogued EQ-5D utility values across various haematologic malignancies but noted a lack of rigorous validation studies tailored to these populations. 7 In lymphoma, limited available data suggest poor sensitivity and known-group validity, raising concerns about its ability to capture disease-specific quality of life impacts. 8 Moreover, many studies rely on trial populations, which may not generalise to broader clinical settings. These gaps highlight the need for targeted validation efforts to ensure that EQ-5D adequately reflects the health status of patients with haematologic malignancies and supports accurate utility estimation for economic evaluations. To address this evidence gap, this study assessed the reliability and validity of the EQ-5D in patients managed in real-world settings for three major haematologic malignancies and examined its performance in capturing the complex HRQoL dimensions of haematologic malignancies in Chinese patients.

Methods

Study design

This cross-sectional observational study assessed HRQoL using EQ-5D and time trade-off (TTO) in patients admitted to a leading tertiary care hospital in China for MM, AL and lymphoma between January and August 2024. Patients were consecutively enrolled during their hospital admissions to ensure a representative sample of real-world clinical scenarios. Ethical approval was obtained from the Xiangya Hospital Ethics Committee (Approval Number: 2024091071), and informed consent was acquired in accordance with the Declaration of Helsinki. Furthermore, the study adhered to the guidelines outlined in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, 9 ensuring methodological rigour and transparency throughout the design, execution and reporting phases.

Study cohort

Clear inclusion and exclusion criteria were established to systematically screen patients admitted to the Department of Haematology at Xiangya Hospital. Inclusion criteria required adult patients with a confirmed primary diagnosis of MM, AL or lymphoma, with hospital admissions directly related to these conditions. Exclusion criteria included patients who declined to participate, those unable to independently complete the EQ-5D survey or TTO evaluation due to cognitive, physical or emotional impairments, and those with significant comorbidities such as unrelated life-threatening conditions.

Patient and public involvement

Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.

Sample size calculation

The sample size was calculated using established methods for determining sample size for correlation coefficients. 10 An expected correlation coefficient of 0.50 between EQ-5D utility index scores and TTO-elicited utility values was assumed, which is classified as a large effect size according to Cohen and is consistent with recommended quality criteria for health status questionnaires. 11 With a two-sided significance level (α) of 0.05 and 90% statistical power (1−β), a minimum sample size of 37 patients was required. The final sample comprised 158 patients (50 with MM, 63 with AL and 45 with lymphoma), which satisfied the minimum sample size requirement for each disease category.

Data collection

EuroQol-5 dimensions-5 levels

Participants completed the validated Chinese version of the EQ-5D survey, which assessed their self-reported HRQoL across five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. 12 13 EQ-5D responses were converted into utility scores using the Chinese EQ-5D utility value set, 14 which reflects health preferences and societal values in China.

Time trade-off

Preference-based utility values were elicited using the validated Chinese version of the TTO questionnaire. 14 15 The TTO elicitation process was supported by trained nurses and conducted via a mobile application that guided participants through a series of hypothetical scenarios. Patients were asked to trade off living 10 years in their current health state for a variable number of years in perfect health. The point of indifference between the two options was recorded as their TTO-derived utility scores. 16

Demographic and clinical characteristics

Demographic characteristics and clinical data were extracted from hospital medical records. Specific clinical data, such as extramedullary involvement for MM patients, extranodal involvement for lymphoma patients and documented central nervous system (CNS) invasion for AL or lymphoma patients, were also collected from medical notes.

Data analysis

Descriptive analysis

Descriptive statistics were used to summarise the demographic and clinical characteristics as well as the utility scores derived from EQ-5D and TTO methods. A paired t-test was used to compare the EQ-5D utility index score and TTO-elicited utility values for the three disease groups, respectively.

Reliability analysis

Reliability refers to the degree to which a measurement instrument produces consistent results. 17 Specifically, it refers to whether different items of a measurement instrument designed to measure the same concept can yield similar results. Cronbach’s α analysis was performed to assess the internal consistency of the EQ-5D instrument across its five dimensions of HRQoL. 18 The Cronbach’s α value ranges from 0 to 1, with higher value indicating better reliability. The Cronbach’s α value greater than 0.7 suggests acceptable reliability. The Cronbach’s α values of EQ-5D were also calculated after each dimension was excluded. An increase in the Cronbach’s α value after exclusion of a dimension suggests potential inconsistency of that dimension with the remaining items, whereas a decrease indicates that the dimension contributes to the overall internal consistency of the EQ-5D.

Criterion validity analysis

Validity is defined as the extent to which a measurement tool can accurately assess the concept that it intends to measure. 17 Criterion validity refers to the degree to which the results of a measurement tool align with a widely recognised criterion. Spearman’s rank correlation was conducted to evaluate the criterion validity, comparing EQ-5D utility scores with TTO-elicited utility values as the reference standard. A Spearman’s rank correlation coefficient greater than 0 indicates a positive correlation, while a coefficient less than 0 indicates a negative correlation. The correlation strength was interpreted as follows: |r|≥0.50 indicates strong correlation, 0.35 ≤ |r|<0.50 indicates moderate correlation, and 0.20 ≤ |r|<0.35 indicates weak correlation.

Structural validity analysis

Structural validity refers to the extent to which a measurement tool can accurately reflect the theoretical structure it intends to measure. Exploratory factor analysis was performed to examine the structural validity of the EQ-5D. 19 Before exploratory factor analysis, Kaiser-Meyer-Olkin (KMO) test and Bartlett’s test of sphericity were applied to determine the adequacy of sampling and the inter-relatedness of EQ-5D dimensions. 20 According to the exploratory factor analysis, key factors were identified based on eigenvalue, explained variance and cumulative explained variance. When two factors were extracted, the cumulative explained variance of all three groups exceeded 75%. To clarify the associations between EQ-5D dimensions and two extracted factors, oblique rotation was conducted to obtain the rotated factor loadings of EQ-5D dimensions on each factor. A rotated factor loading above 0.4 indicates a significant contribution of the corresponding dimension to the factor.

TTO–EQ-5D utility discrepancy

The TTO–EQ-5D utility discrepancy was obtained by calculating the difference between TTO and EQ-5D utility values. To explore the potential sources for the poor validity of EQ-5D utility values in the included patients with AL and lymphoma, multivariate linear regression analyses were conducted to assess the associations between examined patient characteristics and TTO–EQ-5D utility discrepancy. Characteristics with statistically significant regression coefficients were identified as independent factors influencing the difference between the two utility measures. A regression coefficient greater than 0 suggests that the corresponding factor is associated with a lower EQ-5D utility value compared with the TTO value. Conversely, a regression coefficient less than 0 indicates that the factor is associated with a higher EQ-5D utility value relative to the TTO value. All statistical analyses were performed using R software (version 4.4.1). Statistical significance was set at a two-sided p value <0.05.

Results

A total of 158 patients were included in this study: 50 with MM, 63 with AL and 45 with lymphoma. The characteristics of these groups are summarised in table 1 and online supplemental table 1 . Demographically, patients with MM were the oldest (mean age: 58.7 years), while patients with AL were the youngest (mean age: 42.8 years). The proportion of male patients was highest in the MM group (70.0%) and lowest in the lymphoma group (55.6%). Clinically, 8.0% of patients with MM exhibited extramedullary involvement. Among patients with AL, acute myeloid leukaemia, non-M3 was the predominant subtype (76.2%) and 3.2% had CNS involvement. In the lymphoma group, diffuse large B-cell lymphoma (DLBCL) was the most common subtype (37.8%), with 77.8% exhibiting extranodal involvement and 13.3% presenting with CNS involvement. Regarding treatment stage, most patients in all groups were newly diagnosed, but relapsed or refractory cases were more prevalent in MM (32.0%) compared with AL (7.9%) and lymphoma (17.8%).

HRQoL outcomes

HRQoL outcomes varied significantly among the three groups ( figure 1 ). TTO-elicited utility scores indicated that patients with AL had the highest utility (0.798±0.151), followed by lymphoma (0.755±0.220) and MM (0.693±0.174). Across all groups, EQ-5D utility values were consistently higher than TTO-elicited utility.

Reliability of EQ-5D

Reliability analysis of the EQ-5D instrument revealed notable differences across the three disease groups. The MM group exhibited the highest reliability, with a Cronbach’s α of 0.899. Among the individual dimensions, anxiety/depression consistently negatively impacted overall reliability, as evidenced by increased Cronbach’s α scores when this dimension was excluded. In patients with AL and lymphoma, the mobility dimension contributed most to overall reliability, whereas the dimension of usual activities was the most critical dimension for patients with MM. The Cronbach’s α results for the three groups are summarised in table 2 .

Criterion validity of EQ-5D

Criterion validity analysis, assessed using Spearman’s correlation coefficients, revealed varied relationships between EQ-5D utility scores and TTO-elicited utility across the three groups ( figure 2 ). In patients with MM, EQ-5D utility scores were significantly correlated with TTO-elicited utilities (r=0.538, p<0.001). For patients with AL, the correlation was moderate (r=0.386, p=0.002). However, for patients with lymphoma, no significant correlation was observed (r=0.230, p=0.129).

Structural validity of EQ-5D

The structural validity of EQ-5D across the three groups was investigated using exploratory factor analysis, along with KMO and Bartlett’s tests. Patients with MM had the highest KMO value (0.829), followed by patients with AL (0.786) and lymphoma (0.553). Bartlett’s test results were significant (p<0.001) for all groups, confirming the appropriateness of factor analysis. Based on eigenvalues, explained variance and cumulative explained variance, two factors were identified for the three groups ( table 3 ). The explained variance of factor 1 ranged from 43.5% to 52.0%, and inclusion of factor 2 increased the cumulative explained variance to 75.4%–79.2% across the three groups. According to the rotated factor loadings of EQ-5D dimensions on two key factors, we observed that the MM group demonstrated the clearest structural validity ( table 4 ). Factor 1 was mainly associated with physical functioning domains, including mobility, self-care and usual activities. Factor 2 predominantly represented the symptomatic and psychological dimensions, with higher loadings observed for pain/discomfort and anxiety/depression. The EQ-5D also showed acceptable structural validity in patients with AL and lymphoma, whereas the psychological dimension (anxiety/depression) had no significant loadings on either of the two factors.

Patient characteristics influencing the TTO–EQ-5D utility discrepancy

According to the multivariate linear regression analyses examining the association between patient characteristics and the TTO–EQ-5D utility discrepancy in patients with AL and lymphoma, chronic kidney failure was significantly associated with greater utility discrepancy in patients with AL (coefficient=0.213, 95% CI 0.016 to 0.411, p=0.035). Additionally, an ECOG score ≥2 (coefficient=−0.084, 95% CI −0.171 to 0.004, p=0.060) and prior treatment (coefficient=−0.106, 95% CI −0.218 to 0.006, p=0.064) showed non-significant trends towards an association with utility discrepancy in these patients. In contrast, no significant associations were found between the examined characteristics and utility discrepancy in patients with lymphoma, although the ECOG score exhibited a trend towards significance (coefficient=−0.133, 95% CI −0.293 to 0.028, p=0.103). The results of both analyses are presented in figure 3 .

Subgroup analysis

Among the 45 lymphoma patients, 39 patients were non-Hodgkin lymphoma (31 with high-grade lymphoma and eight with low-grade lymphoma) and six were Hodgkin lymphoma ( online supplemental table 2 ). Due to the limited sample size of the low-grade lymphoma and Hodgkin lymphoma subgroups, subsequent EQ-5D analyses were only performed in the high-grade lymphoma subgroup. In line with the results in the overall lymphoma group, the EQ-5D demonstrated strong reliability (Cronbach’s α=0.808, online supplemental table 3 ) and acceptable structural validity ( online supplemental tables 4 and 5 ) but poor criterion validity (no significant correlation with TTO, r=0.203, p=0.273, online supplemental figure 1 ) in patients with high-grade lymphoma. Moreover, we explored whether lymphoma subtypes influenced the TTO–EQ-5D utility discrepancy by multivariate linear regression analyses, which showed that non-Hodgkin lymphoma versus Hodgkin lymphoma (coefficient=−0.109, 95% CI −0.314 to 0.096, p=0.288), high-grade versus low-grade lymphoma (coefficient=−0.006, 95% CI −0.187 to 0.176, p=0.950), or DLBCL versus non-DLBCL (coefficient=0.048, 95% CI −0.094 to 0.190, p=0.498) had no significant impacts on the discrepancy between TTO and EQ-5D utility values.

Discussion

This study evaluated the reliability and validity of the EQ-5D for assessing HRQoL in Chinese patients with three major haematologic malignancies (MM, AL and lymphoma). The EQ-5D demonstrated strong internal consistency across all patient subgroups, with the highest consistency observed in patients with MM. In all three groups, the emotional dimension negatively affected the overall reliability of the EQ-5D. This finding aligns with prior research suggesting that generic instruments like the EQ-5D may struggle to adequately capture psychological distress in cancer populations, 21 where mental health issues are multifaceted and influenced by cultural stigmas surrounding emotional well-being. 22

Significant strong correlations of EQ-5D with TTO-elicited utility scores were observed in patients with MM, but these correlations were weaker in patients with AL and non-significant in patients with lymphoma, highlighting variability in the EQ-5D’s performance across disease groups. The weaker correlations in patients with AL and lymphoma raise questions about the EQ-5D’s sensitivity to specific dimensions in these diseases. For example, anxiety and depression, which are particularly prevalent due to disease uncertainty, 23 24 may be under-reported or inadequately captured by the EQ-5D. 25

The structural validity of the EQ-5D across the three disease groups was confirmed through factor analysis, with most groups meeting thresholds for sampling adequacy and factorability as indicated by KMO and Bartlett’s tests. This study also found that chronic kidney failure was significantly associated with greater discrepancies between TTO and EQ-5D utility values in patients with AL. Patients with chronic kidney failure usually experience physical functioning impairment and physical discomfort, which contributes to relatively lower scores on the EQ-5D. However, the TTO questionnaire focuses on patients’ subjective perceptions of their overall health status, which makes patients take the prognosis of their primary disease as the core consideration, rather than the comorbidity of chronic kidney failure. This may partly explain the observed discrepancy between TTO and EQ-5D utility scores associated with chronic kidney failure. ECOG ≥2 and prior treatment also showed trends toward influencing discrepancies, implying that poorer functional status and treatment history may affect how patients value their health. EQ-5D may be insufficient to effectively reflect the health status of patients with low physical capacity or to accurately capture the potential health damage caused by treatment-related toxicity. In patients with lymphoma, no significant associations were identified. This may be attributed to the limited sample size and different lymphoma subtypes, which reduce statistical power. The observed trend with ECOG score suggests that patient characteristics could still influence discrepancies in this population. These findings are consistent with previous research showing that generic instruments, like EQ-5D, may not fully reflect disease-specific or treatment-specific health burdens in cancer populations. For example, studies have shown that EQ-5D tends to underestimate the impact of fatigue in oncology patients, especially those with advanced disease or comorbidities. 26 Moreover, real-world studies have found that performance status and comorbidities are key drivers of utility variation not fully captured by EQ-5D alone. 7 27

To improve the accuracy of HRQoL measurement, the identified associations can inform utility adjustment strategies. Regression-based mapping algorithms can be developed to adjust EQ-5D values by incorporating patient-level predictors such as ECOG score, comorbidity status and treatment history. For example, Xu et al demonstrated the use of regression models to predict EQ-5D utilities from disease-specific measures and patient characteristics, enhancing the sensitivity of utility estimation in cancer populations. 28 Similarly, Wong et al highlighted that incorporating patient characteristics into mapping models significantly improved the predictive performance of utility estimates. 29 Such adjustments can enhance the validity of EQ-5D in haematologic malignancies and support more accurate quality-adjusted life-year (QALY) estimations in health economic evaluations. Future research should consider developing and validating these adjusted models to better reflect patient-perceived health across diverse clinical contexts.

This study is among the first to comprehensively evaluate the reliability and validity of the EQ-5D in Chinese patients with haematologic malignancies. The study was conducted in line with the current standard research design in this field. The use of EQ-5D assessments alongside TTO, considered a gold standard for preference-based utility, strengthens the robustness of these findings. Subgroup analyses provided nuanced insights into the EQ-5D’s performance across different haematologic malignancies, identifying both strengths and limitations. By focusing on a Chinese population, this study addresses an important gap in the literature and contributes to the global validation of the EQ-5D in diverse cultural contexts. The findings also have important implications for clinical practice. The EQ-5D can be reliably used to assess HRQoL in patients with MM, supporting patient-centred care and shared decision-making. However, for patients with AL and lymphoma, supplementary or disease-specific HRQoL instruments may be needed to more effectively capture psychological and disease-specific health states. 6 30

In summary, this study validated the EQ-5D as a reliable and valid instrument for assessing HRQoL in Chinese patients with haematologic malignancies, particularly in those with MM. The EQ-5D demonstrated strong internal consistency, significant correlations with TTO-elicited utility values and robust structural validity across most dimensions. However, its performance was less robust in patients with AL and lymphoma, underscoring potential limitations in capturing the full spectrum of disease-specific and psychological health states in these populations. Future research is warranted to investigate the underlying factors contributing to the poor performance of EQ-5D in patients with AL and lymphoma and explore complementary instruments or adjusted utility algorithms based on patient characteristics for more accurate measurement of HRQoL.

Limitations

Despite its strengths, this study has several limitations. First, although TTO was adopted as the reference standard for utility valuation, it requires respondents to engage in complex hypothetical trade-offs involving time and health states. Differences in cultural context and conceptual understanding may affect respondents’ valuation processes, potentially contributing to discrepancies between EQ-5D-based and TTO-based utility estimates. Second, this study included only hospitalised patients with haematologic malignancies, and health status was assessed during the inpatient period, which typically reflects a specific stage of disease or treatment. As a result, the findings may not fully represent patients’ HRQoL during more stable phases of daily living. Future longitudinal studies across different disease states and care settings are warranted to further validate the reliability and validity of EQ-5D in this population. Third, this study does not fully explore how lymphoma-specific symptoms impact the EQ-5D’s ability to capture HRQoL, such as complications and discomfort caused by enlarged lymph nodes and various extranodal organ involvement. 31 Forth, the lack of comparison with disease-specific tools, such as the EORTC QLQ-C30, and insufficient subgroup analyses by AL and lymphoma subtypes, stages and treatment statuses further limit the insights into the EQ-5D’s performance. Addressing these gaps with disease-specific tools and patient-centred approaches would enhance the understanding and applicability of the EQ-5D for patients with AL and lymphoma.

Supplementary material

Acknowledgements

We appreciate all the patients involved for allowing us to analyse their clinical data.

Footnotes

Funding: This work was supported by Natural Science Foundation of Hunan Province (2025JJ60487) and China Postdoctoral Science Foundation (GZC20242050 and 2024M763716).

Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2025-109028 ).

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient consent for publication: Not applicable.

Ethics approval: This study involves human participants and was approved by the Xiangya Hospital Ethics Committee (Approval Number: 2024091071). Participants gave informed consent to participate in the study before taking part.

Data availability free text: Data are available from the corresponding author on reasonable request.

Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Data availability statement

Data are available upon reasonable request.

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