Background
Hematological malignancies (HMs) refer to malignant clonal hyperplasia originating from the lymphoid and hematopoietic system [ 1 ], mainly including leukemia, lymphoma, and multiple myeloma (MM). As one of the most common cancers, the absolute number of HMs has been rising in recent decades [ 2 , 3 ]. Although the survival rates of HMs have been improved [ 3 ], the survivors may suffer from treatment-related toxicity, increased risk of second malignancies, and other adverse effect [ 4 , 5 ], resulting in worse health-related quality of life (HRQoL) compared to the general population [ 6 ]. Notably, most HM patients may experience emotional problems such as anxiety or depression, which greatly impair their HRQoL [ 7 , 8 ].
Symptom-specific instruments such as Generalized Anxiety Disorder 7-item scale (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) have been developed focusing on the evaluation of anxiety and depression symptoms [ 9 , 10 ]. The GAD-7 consists of seven questions on anxiety symptoms, such as “feeling nervous, anxious, or on edge” and “not being able to stop or control worrying” [ 10 ]. The PHQ-9 refers to nine items on depression symptoms, such as “little interest or pleasure in doing things” and “feeling down, depressed, or hopeless”. Although the psychometric performance of both the GAD-7 and PHQ-9 have been well validated [ 11 , 12 ], their utilization in routine clinical practice remains suboptimal [ 13 ]. Particularly, patients with HMs often suffer from substantial symptom burden such as intractable pain and persistent fever [ 14 , 15 ], which may limit their ability to complete lengthy psychological assessments.
In recent years, patient-reported outcomes have been increasingly incorporated into clinical practice. Being short and easy to complete, the EQ-5D-5L is among the most commonly used HRQoL instruments in hematology research [ 8 , 16 , 17 ]. The EQ-5D-5L contains five dimensions: Mobility(MO), Self-Care(SC), Usual Activities(UA), Pain/Discomfort(P/D), and Anxiety/Depression(A/D) [ 18 ]. Different from the symptom-specific instruments GAD-7 and PHQ-9, the A/D dimension of EQ-5D-5L evaluates anxiety and depression symptoms through a simple question “feeling worried, sad or unhappy”. The relationship between responses on the A/D dimension and GAD-7/PHQ-9 instruments has been investigated in the general population, which reported that the A/D dimension showed good performance in capturing anxiety and depression symptoms as measured by the GAD-7 and PHQ-9 [ 19 ]. Similar findings have been reported in patients with chronic disease such as diabetes, with strong correlations between A/D dimension and validated symptom-specific instruments [ 20 ]. However, as a single-item measure, the A/D dimension may lack the psychometric depth of dedicated psychological instruments. Previous studies have shown that the performance of A/D dimension was relatively worse in patients with diagnosed anxiety or depression and young individuals [ 19 ]. Another study reported that the A/D dimension exhibited relatively good performance in community settings but substantially lower utility among hospitalized patients [ 21 ]. However, whether the responses on the A/D dimension adequately reflect the anxiety and depression symptoms in patients with HMs remains unexplored.
Therefore, our study aimed to investigate whether the A/D dimension of the EQ-5D-5L, when already collected for HRQoL assessment, correlates with anxiety and depression symptoms and may potentially flag patients who may warrant further psychiatric evaluation.
Methods
Study design
This cross-sectional study was conducted at Xiangya Hospital of Central South University from October 2024 to September 2025. The inclusion criteria were as follows: Patients with a confirmed diagnosis of HM; Patients who could read and understand the questionnaires; Patients aged 18 years or older; Patients who provided informed consent. Eligible patients were invited to complete an anonymous paper-based questionnaire. For this study, all questionnaires with missing values were excluded. The study was approved by the Xiangya Hospital Ethics Committee (Approval No. 2024091071) with written informed consent obtained in accordance with the Declaration of Helsinki.
Research implementation and quality control
The survey was administered by uniformly trained investigators using paper-based questionnaires. To ensure data quality, the following measures were implemented: Standardized training for all investigators; Quality controllers verified data within 24 h of collection, with prompt follow-up to review and clarify questionable entries; Data were double-entered independently by two individuals using Microsoft Excel, followed by logical verification.
EQ-5D-5L A/D dimension
Patients were invited to complete the validated Chinese version of the EQ-5D-5L questionnaire, a tool consisting of five questions that assess five dimensions of HRQoL [ 18 , 22 ]. For the A/D dimension, patients selected the severity level that best reflected their anxiety or depression symptoms from five response levels including “not at all”, “slightly”, “moderately”, “severely”, and “extremely”. Since the GAD-7 and PHQ-9 evaluate anxiety and depression symptoms over the past two weeks, we adjusted the recall period of the EQ-5D-5L questionnaire to two-week timeframe to improve comparability with the GAD-7 and PHQ-9.
GAD-7
Patients were invited to complete the official Chinese version of GAD-7 questionnaire to self-assess the frequency of anxiety-related symptoms during last two weeks [ 10 ]. The GAD-7 is a widely used, well-validated tool for screening anxiety disorders. The seven items of GAD-7 questionnaire cover core anxiety symptoms (for example, tension, uncontrollable worry), with each item rated on a scale of 0 (not at all) to 3 (nearly almost every day). The total score is calculated by summing up the scores of all seven items. Four anxiety severity grades are defined according the total score, including minimal anxiety (no obvious clinical symptoms, 0–4 points), mild anxiety (5–9 points), moderate anxiety (10–14 points), and severe anxiety (15–21 points).
PHQ-9
Patients were also invited to complete the official Chinese version of PHQ-9 questionnaire. The PHQ-9 comprises nine items evaluating the frequency of depression symptoms over the past two weeks [ 23 ]. Its items cover core depression symptoms such as low mood and sleep changes, with each item scored from 0 (not at all) to 3 (nearly almost every day). The total score of PHQ-9 ranges from 0 to 27, categorizing depression severity into five grades: minimal depression (no obvious clinical symptoms, 0–4 points), mild depression (5–9 points), moderate depression (10–14 points), moderately severe depression (15–19 points), and severe depression (20–27 points).
Composite outcome
Given that the A/D dimension covers both anxiety and depression symptoms, we constructed a composite outcome based on the GAD-7 and PHQ-9 scales. The final combined severity classification was determined by adopting the higher grade derived from the two scales. For example, if GAD-7 suggested mild anxiety and PHQ-9 indicated moderate depression, moderate severity was assigned as the final combined classification.
Statistical analysis
Continuous variables were presented by median and interquartile range (IQR) and categorical variables were expressed using proportions. The association between the A/D dimension and GAD-7/PHQ-9 was determined by Spearman’s rank correlation. Spearman’s correlation coefficients were interpreted as follows: weak (< 0.30), moderate (0.30–0.50), moderate-to-strong (0.50–0.70), and strong (≥ 0.70). For intergroup comparisons, continuous variables were analyzed with the Mann–Whitney U test, while categorical variables were evaluated using the chi-square test or Fisher–Freeman–Halton exact test as appropriate. Confidence intervals were calculated using the Wilson method. Scores (e.g., GAD-7 scores) were treated as continuous variables, whereas grades (severity classifications) were regarded as predefined categorical levels. All statistical analyses were performed using R software (version 4.5.1; http://www.R-project.org ) and SPSS (version 28.0; IBM SPSS Inc., Chicago, USA).
Results
Baseline characteristics of patients
A total of 236 HM patients were enrolled in our study. The baseline characteristics of the analyzed patients are summarized in Table 1 . The median age was 43 years old, with a near-equal gender distribution (51.7% male). Most patients (86.9%) had completed secondary education or higher. A relatively high proportion of patients were unemployed (39.4%) and resided in cities (55.9%). Over two-thirds (70.3%) were married. In terms of disease type, nearly half (50.8%) of patients had leukemia, 31.4% had lymphoma, and 14.4% had multiple myeloma. Most patients (75.8%) were diagnosed within three to six months. Additionally, 6.4% of the patients had relapsed or refractory disease. Table 1 Baseline characteristics of study participants Characteristic n = 236 Age, years (median, (Q1, Q3)) 43.0 (27.0, 56.0) Gender Male 122 (51.7%) Female 114 (48.3%) Education Primary or below 31 (13.1%) Secondary 70 (29.7%) Tertiary 59 (25.0%) University or above 76 (32.2%) Employment Full-time 51 (21.6%) Part-time 36 (15.3%) Unemployed 93 (39.4%) Retired 22 (9.3%) Others 34 (14.4%) Residence Cities 132 (55.9%) Towns 32 (13.6%) Rural areas 72 (30.5%) Marriage status Married 166 (70.3%) Unmarried 62 (26.3%) Divorced/widow(er) 8 (3.4%) Disease type Leukemia 120 (50.8%) Lymphoma 74 (31.4%) Multiple myeloma 34 (14.4%) Others 8 (3.4%) Disease duration Less than 3 months 28 (11.9%) 3 to 6 months 179 (75.8%) More than 6 months 29 (12.3%) Relapsed or refractory disease Yes 15 (6.4%) No 221 (93.6%)
Table 1
Baseline characteristics of study participants
| Characteristic | n = 236 |
| Age, years (median, (Q1, Q3)) | 43.0 (27.0, 56.0) |
| Gender | |
| Male | 122 (51.7%) |
| Female | 114 (48.3%) |
| Education | |
| Primary or below | 31 (13.1%) |
| Secondary | 70 (29.7%) |
| Tertiary | 59 (25.0%) |
| University or above | 76 (32.2%) |
| Employment | |
| Full-time | 51 (21.6%) |
| Part-time | 36 (15.3%) |
| Unemployed | 93 (39.4%) |
| Retired | 22 (9.3%) |
| Others | 34 (14.4%) |
| Residence | |
| Cities | 132 (55.9%) |
| Towns | 32 (13.6%) |
| Rural areas | 72 (30.5%) |
| Marriage status | |
| Married | 166 (70.3%) |
| Unmarried | 62 (26.3%) |
| Divorced/widow(er) | 8 (3.4%) |
| Disease type | |
| Leukemia | 120 (50.8%) |
| Lymphoma | 74 (31.4%) |
| Multiple myeloma | 34 (14.4%) |
| Others | 8 (3.4%) |
| Disease duration | |
| Less than 3 months | 28 (11.9%) |
| 3 to 6 months | 179 (75.8%) |
| More than 6 months | 29 (12.3%) |
| Relapsed or refractory disease | |
| Yes | 15 (6.4%) |
| No | 221 (93.6%) |
The association between the A/D dimension and GAD-7/PHQ-9
The association between the A/D dimension of EQ-5D-5L and GAD-7 (for anxiety) and PHQ-9 (for depression) was evaluated. The A/D dimension grade exhibited moderate-to-strong correlation with GAD-7 grade (r = 0.607, P < 0.001) and PHQ-9 grade (r = 0.579, P < 0.001). A statistically significant positive correlation was observed between the A/D dimension and this combined GAD-7/PHQ-9 grade (r = 0.603, P < 0.001).
The performance of the A/D dimension in detecting anxiety/depression
The performance of the EQ-5D-5L A/D dimension in identifying anxiety and depression symptoms was evaluated using GAD-7 and PHQ-9 as reference measures. The A/D dimension of EQ-5D-5L demonstrated high specificity (94.3%; 95% CI, 89.8–96.9%) but low sensitivity (60.0%; 95% CI, 47.1–71.7%) in detecting anxiety of HM patients (Table 2 ). Of 60 HM patients with anxiety confirmed by GAD-7 (defined as GAD-7 ≥ 5), the A/D dimension correctly identified 36 cases (60.0%) but missed 24 cases (40.0%). Of 176 patients without anxiety (defined as GAD-7 < 5), it correctly identified 166 cases (94.3%) but misclassified 10 cases (5.7%). Table 2 Sensitivity and specificity of the A/D dimension in identifying anxiety/depression Outcome A/D dimension Reference positive Reference negative Sensitivity (95% CI) Specificity (95% CI) PPV NPV Anxiety (GAD-7 ≥ 5) Any problems 36 10 60.0% (95% CI: 47.1–71.7%) 94.3% (95% CI: 89.8–96.9%) 78.3% 87.4% No problems 24 166 Depression (PHQ-9 ≥ 5) Any problems 42 4 47.2% (95% CI: 37.0–57.7%) 97.3% (95% CI: 93.2–99.0%) 91.3% 75.3% No problems 47 143 Anxiety/Depression (GAD-7 ≥ 5 and/or PHQ-9 ≥ 5) Any problems 44 2 47.3% (95% CI: 37.2–57.5%) 98.6% (95% CI: 95.0–99.6%) 95.7% 74.2% No problems 49 141
Table 2
Sensitivity and specificity of the A/D dimension in identifying anxiety/depression
| Outcome | A/D dimension | Reference positive | Reference negative | Sensitivity (95% CI) | Specificity (95% CI) | PPV | NPV |
| Anxiety (GAD-7 ≥ 5) | Any problems | 36 | 10 | 60.0% (95% CI: 47.1–71.7%) | 94.3% (95% CI: 89.8–96.9%) | 78.3% | 87.4% |
| No problems | 24 | 166 | |||||
| Depression (PHQ-9 ≥ 5) | Any problems | 42 | 4 | 47.2% (95% CI: 37.0–57.7%) | 97.3% (95% CI: 93.2–99.0%) | 91.3% | 75.3% |
| No problems | 47 | 143 | |||||
| Anxiety/Depression (GAD-7 ≥ 5 and/or PHQ-9 ≥ 5) | Any problems | 44 | 2 | 47.3% (95% CI: 37.2–57.5%) | 98.6% (95% CI: 95.0–99.6%) | 95.7% | 74.2% |
| No problems | 49 | 141 |
The A/D dimension of EQ-5D-5L also had high specificity (97.3%; 95% CI: 93.2–99.0%) but low sensitivity (47.2%; 95% CI: 37.0–57.7%) in assessing depression. Among 89 patients with depression confirmed by PHQ-9 (defined as PHQ-9 ≥ 5), the A/D dimension only correctly identified 42 cases (47.2%).
Since the A/D dimension measures both anxiety and depression, we next combined GAD-7 and PHQ-9 results together for further analysis. The A/D dimension of EQ-5D-5L still had high specificity (98.6%; 95% CI: 95.0–99.6%) in determining both anxiety and depression symptoms, correctly identifying 141 (98.6%) patients out of 143 who had no anxiety or depression. However, its sensitivity was very low (47.3%; 95% CI: 37.2–57.5%), correctly identifying only 47.3% of patients with anxiety or depression.
The positive predictive value (PPV) and negative predictive value (NPV) of the EQ-5D-5L A/D dimension were further evaluated. For anxiety (defined as GAD-7 ≥ 5), the PPV and NPV of the EQ-5D-5L were 78.3% and 87.4%, respectively. For depression (defined as PHQ-9 ≥ 5), the corresponding values were 91.3% and 75.3%. For the combined outcome (defined as GAD-7 ≥ 5 and/or PHQ-9 ≥ 5), the PPV reached 95.7%, whereas the NPV was 74.2% (Table 2 ). Overall, these findings suggest that the A/D dimension has high rule-in value but limited rule-out ability for anxiety/depression symptoms.
The performance of the A/D dimension in identifying anxiety/depression severity levels
As previously stated, the higher grade from the GAD-7 and PHQ-9 questionnaires was defined as the final combined classification for anxiety/depression. Among the 143 patients having no anxiety/depression according to the GAD-7/PHQ-9 questionnaires (GAD-7 ≤ 5 and PHQ-9 ≤ 5), the vast majority (141 patients, 98.6%) also reported no anxiety/depression on the A/D dimension (Table 3 ). This is consistent with the high specificity of the A/D dimension. For the 61 patients classified as having mild anxiety/depression by the GAD-7/PHQ-9, only 20 (32.8%) patients reported mild anxiety/depression on the A/D dimension, while 38 (62.3%) reported no anxiety/depression, and three reported severe or extreme anxiety/depression. Of the 25 patients identified as having moderate anxiety/depression by the GAD-7/PHQ-9, only one patient reported having moderate anxiety/depression on the A/D dimension, while the majority (18 patients, 72.0%) reported either no anxiety/depression or mild anxiety/depression. Additionally, among the five patients with moderately severe anxiety/depression and two patients with severe anxiety/depression as classified by the GAD-7/PHQ-9, all patients reported a lower severity level of anxiety/depression on the A/D dimension. Overall, the A/D dimension effectively identified patients without anxiety or depression, while a significant proportion of patients with anxiety or depression tend to report lower severity levels on the A/D dimension. Table 3 Correspondence between the A/D dimension and GAD-7/PHQ-9 grade levels A/D dimension Combined GAD-7/PHQ-9 grade Minimal (n = 143) Mild (n = 61) Moderate (n = 25) Moderately severe (n = 5) Severe (n = 2) No 141 (98.6%) 38 (62.3%) 10 (40.0%) 1 (20.0%) 0 (0%) Slight 1 (0.7%) 20 (32.8%) 8 (32.0%) 3 (60.0%) 2 (100.0%) Moderate 1 (0.7%) 0 (0%) 1 (4.0%) 1 (20.0%) 0 (0%) Severe 0 (0%) 2 (3.3%) 3 (12.0%) 0 (0%) 0 (0%) Extreme 0 (0%) 1 (1.6%) 3 (12.0%) 0 (0%) 0 (0%)
Table 3
Correspondence between the A/D dimension and GAD-7/PHQ-9 grade levels
| A/D dimension | Combined GAD-7/PHQ-9 grade | ||||
| Minimal (n = 143) | Mild (n = 61) | Moderate (n = 25) | Moderately severe (n = 5) | Severe (n = 2) | |
| No | 141 (98.6%) | 38 (62.3%) | 10 (40.0%) | 1 (20.0%) | 0 (0%) |
| Slight | 1 (0.7%) | 20 (32.8%) | 8 (32.0%) | 3 (60.0%) | 2 (100.0%) |
| Moderate | 1 (0.7%) | 0 (0%) | 1 (4.0%) | 1 (20.0%) | 0 (0%) |
| Severe | 0 (0%) | 2 (3.3%) | 3 (12.0%) | 0 (0%) | 0 (0%) |
| Extreme | 0 (0%) | 1 (1.6%) | 3 (12.0%) | 0 (0%) | 0 (0%) |
Characteristics of patients reporting lower severity level on the A/D dimension
The baseline characteristics of patients who tended to report lower symptom severity on the A/D dimension were analyzed (Table 4 ). Compared with patients with consistent symptom self-reporting, patients who reported lower severity levels on the A/D dimension had a significantly higher education level ( P = 0.036). No significant differences were observed in age, gender, employment, residence, marriage, disease type, disease duration, and disease status between the two groups. Table 4 Comparison of baseline characteristics between patients with lower severity rating and those with consistent severity rating on the A/D dimension Characteristic Lower severity rating (n = 63) Consistent severity rating (n = 162) P value Age, years (median, (Q1, Q3)) 36.0 (25.0, 54.0) 48.5 (31.0, 57.0) 0.056 Gender 0.208 Male 37 (58.7%) 80 (49.4%) Female 26 (41.3%) 82 (50.6%) Education 0.036 Primary or below 5 (7.9%) 26 (16.0%) Secondary 13 (20.6%) 55 (34.0%) Tertiary 20 (31.7%) 36 (22.2%) University or above 25 (39.7%) 45 (27.8%) Employment 0.656 Full-time 15 (23.8%) 34 (21.0%) Part time 6 (9.5%) 16 (9.9%) Unemployed 26 (41.3%) 64 (39.5%) Retired 11 (17.5%) 23 (14.2%) Others 5 (7.9%) 25 (15.4%) Residence 0.342 Cities 38 (60.3%) 83 (51.2%) Towns 6 (9.5%) 26 (16.0%) Rural areas 19 (30.2%) 53 (32.7%) Marriage 0.057 Married 43 (68.3%) 120 (74.1%) Unmarried 20 (31.7%) 34 (21.0%) Divorced/widow(er) 0 (0.0%) 8 (4.9%) Disease Type 0.708 Leukemia 20 (31.7%) 52 (32.1%) Lymphoma 34 (54.0%) 78 (48.1%) Multiple myeloma 9 (14.3%) 24 (14.8%) Others 0 (0.0%) 8 (4.9%) Disease duration 0.152 Less than 3 months 4 (6.3%) 24 (14.8%) 3–6 months 49 (77.8%) 121 (74.7%) More than 6 months 10 (15.9%) 17 (10.5%) Relapsed or refradctory disease 0.118 Yes 1 (1.6%) 12 (7.4%) No 62 (98.4%) 150 (92.6%)
Table 4
Comparison of baseline characteristics between patients with lower severity rating and those with consistent severity rating on the A/D dimension
| Characteristic | Lower severity rating (n = 63) | Consistent severity rating (n = 162) | P value |
| Age, years (median, (Q1, Q3)) | 36.0 (25.0, 54.0) | 48.5 (31.0, 57.0) | 0.056 |
| Gender | 0.208 | ||
| Male | 37 (58.7%) | 80 (49.4%) | |
| Female | 26 (41.3%) | 82 (50.6%) | |
| Education | 0.036 | ||
| Primary or below | 5 (7.9%) | 26 (16.0%) | |
| Secondary | 13 (20.6%) | 55 (34.0%) | |
| Tertiary | 20 (31.7%) | 36 (22.2%) | |
| University or above | 25 (39.7%) | 45 (27.8%) | |
| Employment | 0.656 | ||
| Full-time | 15 (23.8%) | 34 (21.0%) | |
| Part time | 6 (9.5%) | 16 (9.9%) | |
| Unemployed | 26 (41.3%) | 64 (39.5%) | |
| Retired | 11 (17.5%) | 23 (14.2%) | |
| Others | 5 (7.9%) | 25 (15.4%) | |
| Residence | 0.342 | ||
| Cities | 38 (60.3%) | 83 (51.2%) | |
| Towns | 6 (9.5%) | 26 (16.0%) | |
| Rural areas | 19 (30.2%) | 53 (32.7%) | |
| Marriage | 0.057 | ||
| Married | 43 (68.3%) | 120 (74.1%) | |
| Unmarried | 20 (31.7%) | 34 (21.0%) | |
| Divorced/widow(er) | 0 (0.0%) | 8 (4.9%) | |
| Disease Type | 0.708 | ||
| Leukemia | 20 (31.7%) | 52 (32.1%) | |
| Lymphoma | 34 (54.0%) | 78 (48.1%) | |
| Multiple myeloma | 9 (14.3%) | 24 (14.8%) | |
| Others | 0 (0.0%) | 8 (4.9%) | |
| Disease duration | 0.152 | ||
| Less than 3 months | 4 (6.3%) | 24 (14.8%) | |
| 3–6 months | 49 (77.8%) | 121 (74.7%) | |
| More than 6 months | 10 (15.9%) | 17 (10.5%) | |
| Relapsed or refradctory disease | 0.118 | ||
| Yes | 1 (1.6%) | 12 (7.4%) | |
| No | 62 (98.4%) | 150 (92.6%) |
Discussion
Patients with HMs frequently experience significant psychological distress, with approximately one in five suffering from anxiety or depression symptoms [ 24 ]. It has been reported that anxiety and depression symptoms are significantly associated with increased cancer-specific mortality risk in HM patients [ 25 ]. HM patients with anxiety or depression had significantly shorter overall survival compared to their counterparts without these psychological conditions [ 25 , 26 ]. Therefore, systematic screening and early identification for anxiety/depression symptoms in this population is clinically meaningful.
Our study is the first to evaluate the relationship between the A/D dimension of EQ-5D-5L and symptom-specific measures of anxiety and depression in patients with HMs. Our results indicated that the A/D dimension showed moderate-to-strong correlation with the GAD-7 and PHQ-9, suggesting that the A/D dimension may reflect psychological distress at the population level. These findings are consistent with previous studies in the general population and patients with diabetes [ 19 , 20 ]. However, such correlations between the A/D dimension and symptom-specific instruments at the group level do not necessarily indicate adequate screening performance. Our further analysis demonstrated that the A/D dimension had low sensitivity (47.2–60.0%) in identifying patients with anxiety or depression symptoms defined by GAD-7 or PHQ-9. The NPV was also relatively low, meaning that about one-quarter of patients classified as having “no problems” on the A/D dimension still had unrecognized anxiety or depression symptoms. An effective psychological screening tool should generally achieve a sensitivity of at least 70% – 80% [ 27 , 28 ]. Therefore, the A/D dimension of the EQ-5D-5L alone may not be sufficient as an independent screening tool for anxiety or depression. Unlike GAD-7 and PHQ-9 which contains multiple domains of anxiety and depression symptoms, the A/D dimension relies on a single question about emotional distress. Patients might perceive the single-item A/D dimension as a formal diagnostic tool rather than a subjective reporting instrument, leading them to deliberately minimize symptoms to avoid being assigned a clinical label. In addition, all participants included in this study were inpatients. The hospital environment may intensify psychological defensiveness and distort self-assessment authenticity among distressed patients. Such response bias may be more pronounced for the single-item A/D dimension when compared with multi-item scales such as GAD-7 and PHQ-9.
In contrast, the A/D dimension showed relatively high specificity (94.3–98.6%). Moreover, the PPV for the A/D dimension was also high, suggesting that most patients identified as positive by the A/D dimension truly had anxiety or depression symptoms. These findings suggest that the A/D dimension may be more suitable as a “rule-in” tool rather than a “rule-out” tool for anxiety and depression symptoms. In other words, patients with positive results on the A/D dimension should undergo further assessment using GAD-7, PHQ-9, or other specific psychological evaluation. Negative results on the A/D dimension cannot sufficiently rule out potential psychological problems in this vulnerable population.
Further analysis revealed that HM patients who reported lower severity levels on the A/D dimension had a higher education level than those providing consistent reports. Similar to our findings, a previous study in general population also found that the performance of the A/D dimension was worse in highly educated individuals than in the low and middle educated individuals [ 19 ]. One possible explanation is that respondents may adopt different internal standards when rating on the A/D dimension of EQ-5D-5L. Patients with higher educational level may tend to apply stricter thresholds when interpreting general emotional items in HRQoL measures, which typically assess broad emotional well-being rather than specific anxiety or depression symptoms [ 29 ]. However, since our analysis was exploratory and unadjusted, further larger sample studies are needed to validate the influence of education background on responses to the generic psychological item in HRQoL instruments.
Taken together, these findings indicate that the A/D dimension of EQ-5D-5L could reflect overall psychological distress at the population level but has limited ability to identify symptomatic individuals in clinical settings. The low sensitivity suggests that the A/D dimension is not suitable as a standalone screening tool for anxiety or depression in patients with HMs. Relying solely on this dimension would fail to identify a substantial number of patients with psychological symptoms, especially in patients with higher education background. Negative responses on the A/D dimension may not rule out the possibility of underlying psychological distress. Nevertheless, its high specificity indicates that patients reporting problems on the A/D dimension are likely to have clinically significant psychological distress and may benefit from further psychological assessment. Therefore, in clinical practice, the A/D dimension may serve as a supplementary indicator within routine HRQoL assessment rather than a substitute for validated psychological screening instruments.
Study limitations
There are several limitations in our study. First, this study was conducted with a relatively small sample size in China, which may restrict the generalizability of our findings. In the Chinese cultural contexts, disease-related stigma and restrained emotional expression may reduce patients’ willingness to report psychological distress [ 30 – 33 ]. Therefore, future multi-center collaborations are warranted to validate our findings across different ethnic, cultural, and healthcare contexts. Second, our study modified the EQ-5D-5L recall period from “today” to “the past two weeks” to align with the time frame of GAD-7 and PHQ-9, which may affect the original psychometric properties of the instrument. However, existing evidence has indicated that longer recall periods may better capture symptom burden and self-perceived health status in patient-reported outcome assessments [ 34 , 35 ]. In addition, aligning the recall period across different tools enhances methodological consistency, enabling more reasonable and comparable correlation analysis between the EQ-5D-5L A/D dimension and dedicated anxiety and depression scales. Third, different pathological subtypes of HMs were combined for analysis in the present study. We further performed subgroup analysis which indicated that disease subtypes had no significant impact on the performance of the A/D dimension. Fourth, longitudinal follow-up is needed to investigate whether the performance of the A/D dimension dynamically changes under different disease conditions.
Conclusions
In summary, the A/D dimension of the EQ-5D-5L exhibited moderate-to-strong agreement with symptom-specific measures of anxiety and depression among HM patients. Given its limited sensitivity but high specificity, the A/D dimension may be more appropriate as a supplementary indicator rather than a standalone screening tool for anxiety and depression symptoms. Combining HRQoL instruments with specialized psychological screening scales in routine clinical practice is recommended to facilitate comprehensive psychological assessments.
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Author contributions
Y. X. conceived the study, supervised the research, and revised the manuscript. W. Q. performed the data analyses and wrote the manuscript. F. T. performed the data collection and analysis, and wrote the manuscript. Y. Z., T. C., S. W., and Y. C. made substantial contribution to data collection and analyses. All authors have critically reviewed and approved the final manuscript.
Funding
This work was supported by National Natural Science Foundation of China (81974002), Health Development Promotion—Spark Development Project (XHJH-0032), Translational Research Grant of NCRCH (2021WWC02), Hunan Provincial Natural Science Foundation of China (2025JJ60487) and China Postdoctoral Science Foundation (GZC20242050 and 2024M763716).
Data availability
The data are available from the lead and corresponding authors upon reasonable requests.
Declarations
Conflict of interest
The authors declare no conflict of interests.
Ethical approval
The study was approved by the Xiangya Hospital Ethics Committee with written informed consent obtained in accordance with the Declaration of Helsinki.
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