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. 2020 Dec 3;15(12):e0243357. doi: 10.1371/journal.pone.0243357

The Hospital Anxiety and Depression Scale (HADS) applied to Ethiopian cancer patients

Yemataw Wondie 1, Anja Mehnert 2, Andreas Hinz 2,*
Editor: Rosemary Frey3
PMCID: PMC7714130  PMID: 33270779

Abstract

Psychological distress is a common problem associated with cancer. The main objective of the present study was to test the Hospital Anxiety and Depression Scale (HADS) in a sample of Ethiopian cancer patients and to compare the results with those obtained from a sample in Germany. Data were collected from 256 cancer patients who visited the University of Gondar Hospital between January 2019 and June 2019 using the HADS, the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), and the Multidimensional Fatigue Inventory MFI-20. The reliability of the HADS was good, with Cronbach’s α coefficients of 0.86 (anxiety), 0.85 (depression), and 0.91 (total scale). The Ethiopian cancer patients were more anxious (M = 7.9) and more depressed (M = 9.3) than the German patients (M = 6.8 for anxiety and M = 5.5 for depression). Only a weak level of measurement invariance was detected between the Ethiopian and the German sample. In the Ethiopian sample, anxiety and depression were associated with tumor stage (high levels in stage 4) and treatment (high levels for patients not receiving surgery and chemotherapy). Both anxiety and depression were significantly associated with all of the EORTC QLQ-C30 and MFI-20 scales. The HADS proved to be applicable for use with Ethiopian cancer patients. The high level of anxiety and depression present in that group indicates a need for psychosocial care.

Introduction

Cancer incidence and mortality rates are lower in low-income countries (LICs) than in high-income countries (HICs). Of the 7.6 billion people alive on earth in 2018, about 1.3 billion people (17%) resided in Africa. As far as cancer incidence rates are concerned, Africa accounts for only 4.7 percent of cases worldwide, and the incidence of cancer mortality (5.9%) there is only slightly higher [1]. Nevertheless, cancer incidence and mortality rates are increasing in LICs such as Ethiopia, mainly due to increases in life expectancy [27]. Mental health care for oncological patients is however not well established in LICs, and knowledge about the status of patients’ mental health in those countries is very limited. Nonetheless, some studies have been performed to investigate mental health and quality of life (QoL) in specific samples of Ethiopian cancer patients. Most of these were conducted in the capital, Addis Ababa, among patients suffering from breast or gynecologic cancer [811].

Anxiety and depression are common psychological symptoms in cancer patients [1215]. These symptoms can affect QoL, adherence to treatment, cancer survival, and treatment costs [1618]. The Hospital Anxiety and Depression Scale (HADS), developed by Zigmond and Snaith [19], is one of the most frequently used instruments for measuring anxiety and depression in patients suffering from physical illness, including cancer. It has been applied to a wide range of diseases [20], and multiple studies have been performed to test psychometric properties of the scale [2124]. Most of the psycho-oncological studies that have used the HADS have been conducted in HICs. A particular problem in LICs is illiteracy. In Ethiopia, where the literacy rate is low, many patients cannot fill in questionnaires without help. In previous Ethiopian studies done on QoL in cancer patients [8,10,25], more than 50% of the patients were illiterate or never went to school. In such cases, research assistants must read the questions aloud, ask the patients to respond verbally, and mark the response in the questionnaire. It has not yet been systematically studied whether this method of data collection has a substantial impact on the outcome.

Measurement invariance of the instrument used is an important issue to consider when comparing the mean scores of different samples. To our knowledge, measurement invariance of the HADS had never previously been tested in a comparison between a HIC and a LIC. We therefore also tested the measurement invariance of the HADS by comparing an Ethiopian and a German sample of cancer patients.

Multiple examinations have been performed to study the impact of sociodemographic and clinical variables on anxiety and depression [15,2628]. One typical result was that female cancer patients were generally more anxious than male patients [15,27,29]. Most of these studies have also been performed in HICs, and it is unclear to what degree the results are also applicable to LICs.

The general objective of this study was to test psychometric properties of the HADS in a sample of Ethiopian cancer patients and to compare the results with those obtained in Germany, a country with a longer tradition of applying this questionnaire. In particular, the aims were (a) to explore the degree of anxiety and depression in Ethiopian cancer patients in comparison with German cancer patients, (b) to analyze the impact of sociodemographic and clinical variables on anxiety and depression, (c) to test psychometric properties of the HADS, (d) to compare the applicability of the scale in the Ethiopian context with the German context via measurement invariance analysis, and (e) to analyze the relationship between the HADS scales and several facets of QoL.

Methods

Ethiopian cancer patients

The present study was conducted at the University of Gondar Specialized Hospital, Ethiopia. Gondar is the second largest city in Ethiopia, with a population of about 300,000 inhabitants. Between January 2019 and June 2019, 298 cancer patients treated at this hospital were eligible for this study. Participants were invited to take part in the study if they had a malignant tumor of any cancer site and disease stage, were at least 18 years old, and understood Amharic, the national language of Ethiopia and that predominantly spoken in Gondar and its surroundings. Tumor entities, disease stage, and illiteracy did not serve as exclusion criteria. Trained nurse research assistants contacted the patients, explained the aims of the study, and asked them to participate and give informed consent. If the patients were illiterate, the research assistants read the questions aloud, asked the patients to respond verbally, and marked the response in the questionnaire. Medical data was taken from the medical records kept by the hospital. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of the University of Gondar (Ref. No. O/V/P/RCS/05/1542/2018; dated June 18, 2018).

German cancer patients

A group of German cancer patients served as controls. The patients were recruited in five study centers in Germany. Further details of the sample are published elsewhere [30]. Data on anxiety and depression in this sample have already been published [28]. The sample consisted of 1,821 males and 1,964 females with a mean age of 58.3 years. Because of the differences in the age and gender distribution between the Ethiopian and the German samples, we selected a subsample of the German cancer patients matched to the Ethiopian one in those aspects. The resulting German subsample consisted of 1,664 cancer patients, of which 638 (38.3%) and 1,026 (61.7%) were males and females, respectively. The mean age of this group was 48.0 years. All participants gave informed consent. This study was also conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committees of each of the five participating universities: the Ethics Committee of the University of Leipzig, the Ethics Committee of the University of Hamburg, the Ethics Committee of the University of Freiburg, the Ethics Committee of the University of Heidelberg, and the Ethics Committee of the University of Würzburg.

Questionnaires

The HADS consists of 14 items. Seven of the items indicate anxiety and the remaining seven items indicate depression. The answer format offers four response options, which are scored with values ranging from 0 to 3. This results in scale values between 0 and 21 for each scale. The original test authors defined three ranges for both of the scales: 0–7 (non-cases), 8–10 (doubtful cases), and 11–21(cases). It is possible to calculate a HADS total score by simply summing up the anxiety and depression items [31]. Normative values are available for several countries [3235]. The Amharic translation of the HADS was adopted from a study conducted among Ethiopian HIV patients [36].

Two other questionnaires were used in addition to the HADS. The European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) [37] is comprised of 30 items which are assigned to five functioning scales (physical, role, emotional, social, and cognitive functioning), three symptom scales (fatigue, pain, and nausea/vomiting), a two-item global health /QoL scale, and six single item scales (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Higher functioning scores represent better functioning/QoL, whereas higher symptom scores represent more severe symptoms. A sum score of the EORTC QLQ-C30 can be calculated, following a recommendation of the EORTC Quality of Life Group [38]. The Multidimensional Fatigue Inventory (MFI-20) [39] was used to measure fatigue. It assesses five dimensions of fatigue: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Each subscale consists of four items, scored with values from 1 to 5. Higher scores reflect a higher level of fatigue. We also calculated a sum score for all 20 items.

Statistical analysis

Mean score differences were expressed in terms of Cohen’s effect sizes d. Reliability was measured with Cronbach’s coefficient α. To test the impact of sociodemographic and clinical variables on anxiety and depression, we used three-factor ANOVAs with gender and age group as cofactors. Confirmatory Factor Analyses (CFAs) were calculated to test the two-dimensional structure of the HADS. The measurement invariance between the Ethiopian and the German data set was analyzed with measurement invariance analyses using the criteria Chi2/df, Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), Root Mean Square Error of Approximation (RMSEA), and Standardized Root Mean Square Residual (SRMR). The associations between the HADS scales and scales of other questionnaires were expressed with Pearson correlations. The CFA statistics were performed with Mplus, and all other statistics were calculated with SPSS version 24.

Results

Sociodemographic characteristics of the Ethiopian sample

Of the 298 patients eligible for participation in the study, 256 (85.9%) were gave informed consent and filled in the questionnaires. The research assistants proofed the questionnaires so that there remained no missing items in the questionnaires. Of the 256 participants, 135 (52.7%) were illiterate. Further sociodemographic and clinical variables are given in Table 1. The most frequent cancer types were breast cancer (25.4%), colon cancer (17.2%), and non-Hodgkin lymphoma (14.5%).

Table 1. Characteristics of the sample of Ethiopian cancer patients.

Males Females Total
(n = 99) (n = 157) (n = 256)
n % n % n %
Age (years)
    M (SD) 51.6 15.8 45.6 13.3 M = 47.9 SD = 14.6
Age category
    18–49 y. 37 37.4 90 57.3 127 49.6
    ≥ 50 y. 62 62.6 67 42.7 129 50.4
Marital status
    Single 16 16.2 23 14.6 39 15.2
    Married 76 76.8 82 52.2 158 61.7
    Divorced 7 7.1 30 19.1 37 14.5
    Separate /Widowed 0 0.0 22 14.0 22 8.6
Education
    Illiterate 48 48.5 87 55.4 135 52.7
    Elementary school 19 19.2 19 12.1 38 14.8
    Secondary school 13 13.1 18 11.5 31 12.1
    High school 5 5.1 7 4.5 12 4.7
    Technical and vocational college 9 9.1 16 10.2 25 9.8
    University 5 5.1 10 6.4 15 5.9
Religion
    Christian 89 89.9 141 89.8 230 89.8
    Muslim 10 10.1 16 10.2 26 10.2
Tumor
    Breast 2 2.0 63 40.1 65 25.4
    Colon 24 24.2 20 12.7 44 17.2
     Non-Hodgkin lymphoma 22 22.2 15 9.6 37 14.5
    Cervix uteri 0 0.0 15 9.6 15 5.9
    Corpus uteri 0 0.0 9 5.7 9 3.5
    Prostate 9 9.1 0 0.0 9 3.5
    Colorectal 3 3.0 5 3.2 8 3.1
    Thyroid 2 2.0 6 3.8 8 3.1
    Lymphocytic lymphoma 2 2.0 4 2.5 6 2.3
    Pancreas 5 5.1 1 0.6 6 2.3
    Lung 4 4.0 2 1.3 6 2.3
    Other 26 26.3 17 10.8 43 16.8
Tumor stage, UICC a
    1 5 5.1 15 9.6 20 7.8
    2 20 20.2 46 29.3 66 25.8
    3 22 22.2 41 26.1 63 24.6
    4 26 36.4 44 28.0 80 31.3
Surgery
    No 56 56.6 69 43.9 125 48.8
    Yes 43 43.4 88 56.1 131 51.2
Radiation
    No 90 90.9 144 91.7 234 91.4
    Yes 9 9.1 13 8.3 22 8.6
Chemotherapy
    No 46 46.5 63 40.1 109 42.6
    Yes 53 53.5 94 59.9 147 57.4

Note.

a Missing data not reported.

In the German sample, the most frequent cancer localizations were: breast (29.0%), digestive organs (18.8%), female genital organs (9.9%), blood and blood forming organs (9.1%), male genital organs (8.1%), and respiratory organs (7.4%). The distribution of the tumor stage in the German sample was: stage 1 (22.2%), stage 2 (24.3%), stage 3 (20.9%), and stage 4 (32.6%).

Psychometric analyses on scale level and item level

The right part of Table 2 shows (part-whole-corrected) item-test correlations for the items and reliability coefficients (Cronbach’s α) for the scales. All α coefficients of the Ethiopian sample were good (α ≥ 0.85) end even slightly higher than the coefficients obtained from the German sample. All items contributed positively to the scale scores with coefficients between 0.53 and 0.67.

Table 2. HADS mean scores and psychometric criteria, comparison between Ethiopia and Germany.

Ethiopia Germany Effect Ethiopia Germany
Items M (SD) M (SD) size d rit rit
    A1: Tense, wound up 1.23 (0.88) 1.07 (0.76) 0.20 0.65 0.57
    A3: Frightened feeling 1.19 (0.96) 1.27 (0.96) -0.08 0.64 0.61
    A5: Worries 1.14 (0.97) 1.04 (0.83) 0.11 0.64 0.66
    A7: Relaxed 1.20 (0.93) 0.99 (0.81) 0.24 0.62 0.61
    A9: Butterflies 1.04 (0.80) 0.90 (0.72) 0.18 0.65 0.60
    A11: Restless 1.08 (0.88) 0.98 (0.90) 0.11 0.64 0.33
    A13: Panic 0.98 (0.80) 0.57 (0.72) 0.54 0.60 0.63
    D2: Enjoy things 1.39 (1.00) 0.77 (0.79) 0.69 0.67 0.70
    D4: Laugh/funny side 1.33 (0.92) 0.66 (0.75) 0.80 0.61 0.72
    D6: Cheerful 1.04 (0.83) 0.78 (0.85) 0.31 0.65 0.69
    D8: Slowed down 1.69 (1.01) 1.41 (0.83) 0.30 0.61 0.49
    D10: Appearance 1.11 (0.97) 0.43 (0.73) 0.80 0.58 0.43
    D12: Enjoyment 1.11 (0.98) 0.99 (0.91) 0.13 0.67 0.67
    D14: Book/TV 1.68 (1.13) 0.48 (0.70) 1.31 0.53 0.56
Scales
    Anxiety 7.9 (4.6) 6.8 (4.0) 0.26 α = 0.86 α = 0.82
    Depression 9.3 (5.0) 5.5 (4.1) 0.84 α = 0.85 α = 0.85
    Total score 17.2 (9.0) 12.3 (7.4) 0.60 α = 0.91 α = 0.89

Note. d: Effect size of the difference between the Ethiopian and the German mean scores; rit: Part-whole-corrected item-test correlations.

The comparison between the Ethiopian and the German mean scores indicates that the Ethiopian patients had higher levels of psychological burden than the German patients. This difference was especially high in the depression scale. All but one of the 14 items showed higher means in the Ethiopian sample. One item (A3: frightened feeling) showed an opposite trend. The greatest difference between the Ethiopian and the German cancer patients was found for the depression item D14, whereby an effect size of greater than 1 was observed. The distributions of the three categories (no, doubtful, severe cases of anxiety and depression) in the two samples are presented in Table 3.

Table 3. Categorical distribution of anxiety and depression.

Ethiopia Germany
Anxiety Depression Anxiety Depression
n % n % N % n %
No cases 129 50.4 85 33.2 995 59.8 1172 70.4
Doubtful cases 48 18.7 61 23.8 337 20.3 268 16.1
Severe cases 79 30.9 110 43.0 332 20.0 224 13.5

Measurement invariance between the Ethiopian and German samples’ HADS scores

The results of two-factor CFA of the Ethiopian sample are illustrated in Fig 1. The latent variables of anxiety and depression were correlated with r = 0.88, whereas the correlation of the mean scores of anxiety and depression was r = 0.75. All item loadings were between 0.55 and 0.76, the lowest loading was found for item D14 (book/TV), with a coefficient of 0.55.

Fig 1. CFA results for the Ethiopian sample.

Fig 1

The fit indices are given in the upper part of Table 4. CFI and TLI were higher than 0.90 for both the Ethiopian and the German sample.

Table 4. Results of the measurement invariance analyses.

Level of invariance Ethiopia vs. Germany Chi2 (df) Chi2/df CFI TLI RMSEA SRMR
Configural invariance Ethiopia (N = 256) 204.80 (76) 2.70 0.919 0.903 0.082 0.052
Germany (N = 1664) 756.40 (76) 9.95 0.930 0.917 0.073 0.043
Baseline Unconstrained 961.46 (152) 6.33 0.929 0.915 0.053 0.052
Metric (weak) invar. Weights fixed 1053.59 (166) 6.35 0.922 0.914 0.053 0.117
Scalar (strong) invar. Weights and intercepts fixed 1452.0 (176) 8.25 0.888 0.884 0.061 0.101
Full (strict) invar. All parameters fixed 2059.8 (191) 10.78 0.835 0.843 0.071 0.111
Fit differences
Level of invariance Model comparison ΔCFI ΔTLI ΔRMSEA ΔSRMR
Metric (weak) invar. Weights fixed vs. baseline -0.007 -0.001 0.000 0.065
Scalar (strong) invar. Weights and intercepts fixed vs. weights fixed -0.034 -0.030 0.008 -0.016
Full (strict) invar. All parameters fixed vs. weights and intercepts fixed -0.053 -0.041 0.010 0.010

While the criteria for metric (weak) invariance were fulfilled, scalar (strong) invariance was not supported since the CFI and TLI coefficients were lower than 0.90, and SRMR was higher than 0.10. The model fit for strict invariance was even less satisfying than that for the strong invariance. The lower part of Table 4 documents the differences in the fit indices between subsequent models.

The impact of sociodemographic and clinical variables on anxiety and depression

Table 5 shows the impact of sociodemographic and clinical variables on anxiety and depression in the Ethiopian sample. Neither age nor gender was significantly associated with anxiety and depression. Patients with low levels of education were more depressed than their better-educated counterparts. There was a nearly linear increase of anxiety and depression with tumor stage. Patients who received surgery or chemotherapy were less anxious and less depressed than patients who were not receiving cancer treatment (Table 5).

Table 5. HADS mean scores of the Ethiopian sample, depending on sociodemographic and clinical variables.

n Anxiety Depression
M (SD) M (SD)
Gender
    Male 99 8.0 (4.8) 9.5 (4.7)
    Female 157 7.8 (4.5) 9.2 (5.2)
    (Significance) (F = 0.328) (p = 0.568) (F = 0.050) (p = 0.824)
Age group
    ≤ 49 years 127 8.0 (4.7) 8.9 (5.2)
    ≥ 50 years 129 7.7 (4.6) 9.8 (4.7)
    (Significance) (F = 0.829) (p = 0.363) (F = 1.836) (p = 0.177)
Marital status
    Single 39 8.5 (4.2) 9.4 (4.8)
    Married 158 7.7 (4.8) 9.2 (5.0)
    Divorced, widowed 59 8.0 (4.4) 9.7 (5.0)
    (Significance) (F = 0.325) (p = 0.723) (F = 0.446) (p = 0.640)
Education
    Illiterate 135 8.4 (4.5) 10.5 (4.8)
    Elem. and sec. school 69 7.0 (4.7) 8.5 (4.8)
    High school and above 22 7.9 (4.7) 7.1 (5.0)
    (Significance) (F = 1.907) (p = 0.151) (F = 8.523) (p<0.001)
Tumor type
    Breast 65 6.3 (4.6) 7.9 (5.6)
    Colon 44 7.2 (4.1) 8.7 (4.4)
    Non-Hodgkin lymphoma 37 9.2 (5.0) 10.3 (5.2)
    Others 110 8.6 (4.4) 10.1 (4.5)
    (Significance) (F = 2.322) (p = 0.076) (F = 1.215) (p = 0.305)
Stage
    1 20 7.0 (3.5) 8.4 (3.7)
    2 66 6.7 (4.2) 8.5 (4.4)
    3 63 7.5 (5.0) 8.2 (5.3)
    4 80 8.5 (4.7) 10.5 (5.0)
    (Significance) (F = 2.084) (p = 0.103) (F = 3.313) (p = 0.021)
Surgery
    No 125 9.2 (4.5) 10.9 (4.7)
    Yes 131 6.6 (4.4) 7.8 (4.8)
    (Significance) (F = 22.869) (p<0.001) (F = 20.587) (p<0.001)
Chemotherapy
    No 109 8.7 (4.4) 10.3 (4.9)
    Yes 147 7.3 (4.7) 8.6 (4.9)
    (Significance) (F = 6.269) (p = 0.013) (F = 6.732) (p = 0.010)

Comparison between illiterate and literate patients

Since education had a significant impact on depression, we looked for the items that contributed most significantly to this difference. To do so, we calculated the 14 item mean scores for the 135 illiterate patients and those 121 patients with school education separately, and we expressed the group differences in terms of effect sizes (Table 6). All of the illiterate subgroup’s item mean scores were equal or higher than those of the other group. The effect sizes of the seven anxiety items ranged from 0.00 to 0.32 and from 0.13 to 0.79 for the depression items. The highest differences were found for item D14 (books/TV) (d = 0.79), while all of the other items had effect sizes below 0.50. Item D14 was also the item with the lowest loadings in Fig 1 and the largest group differences between the Ethiopian and the German cancer patients (Table 2). It is understandable that enjoyment of reading books and watching TV depends on a person’s ability to read and their access to TV devices. Therefore, we also calculated several analyses excluding this item. When the depression scale was based on the remaining six items, Cronbach’s α coefficient remained unchanged (α = 0.85), and the effect size for the depression difference between Ethiopia and Germany reduced from d = 0.84 to d = 0.66. When we allowed the intercept of item D14 to be different in the measurement invariance analysis (Table 4), scalar (strong) invariance was approached. Based on the assumption that the other 13 items have equal intercepts and only item D14 was allowed to have different parameters, the following coefficients were obtained: Chi2(175) = 1302.92, Chi2/df = 7.445, CFI = 0.901, TLI = 0.897, and RMSEA = 0.058.

Table 6. Item mean scores for illiterate and literate patients.

Illiterate Literate Effect size d
M (SD) M (SD)
Items
    A1: Tense, wound up 1.33 (0.92) 1.12 (0.82) 0.24
    A3: Frightened feeling 1.23 (0.92) 1.15 (1.00) 0.08
    A5: Worries 1.27 (0.96) 0.98 (0.97) 0.30
    A7: Relaxed 1.33 (0.95) 1.04 (0.89) 0.32
    A9: Butterflies 1.04 (0.72) 1.04 (0.88) 0.00
    A11: Restless 1.13 (0.87) 1.03 (0.90) 0.11
    A13: Panic 1.02 (0.76) 0.94 (0.84) 0.10
    D2: Enjoy things 1.55 (0.97) 1.21 (1.02) 0.34
    D4: Laugh/funny side 1.42 (0.92) 1.22 (0.92) 0.22
    D6: Cheerful 1.09 (0.76) 0.98 (0.89) 0.13
    D8: Slowed down 1.91 (1.00) 1.44 (0.97) 0.48
    D10: Appearance 1.22 (0.99) 0.98 (0.93) 0.25
    D12: Enjoyment 1.27 (0.91) 0.94 (1.03) 0.34
    D14: Book/TV 2.07 (1.01) 1.24 (1.09) 0.79
Scales
    Anxiety 8.36 (4.51) 7.31 (4.69) 0.23
    Depression 10.53 (4.79) 8.02 (4.87) 0.52
    Total score 18.90 (8.69) 15.33 (8.95) 0.40

Illiteracy was confounded with several variables. Among the illiterate patients the proportion of older patients was higher (p = 0.001), and the proportions of patients receiving surgery and chemotherapy was lower (p = 0.002 and p = 0.004, respectively) than in the group of literate patients. There were no statistically significant associations between illiteracy and gender, marital status, tumor type, and tumor stage.

Correlations with other scales

Correlations between the HADS scores and the scales of the EORTC QLQ-C30 and the MFI-20 are presented in Table 7. Despite the peculiarity of item D14, we used the original scales with seven items each. Anxiety and depression were most strongly correlated with the MFI-20 fatigue sum score and with the sum score of the EORTC QLQ-C30. The correlations were very similar for the anxiety and depression subscale of the HADS.

Table 7. Correlations between the HADS scores and scales of other questionnaires.

Anxiety Depression Total score
EORTC QLQ-C30
    Physical functioning -.49 *** -.57 *** -.57 ***
    Role functioning -.53 *** -.57 *** -.59 ***
    Emotional functioning -.65 *** -.57 *** -.65 ***
    Cognitive functioning -.60 *** -.61 *** -.64 ***
    Social functioning -.55 *** -.55 *** -.59 ***
    Global health/QoL -.50 *** -.53 *** -.55 ***
    Fatigue .57 *** .64 *** .65 ***
    Nausea/Vomiting .38 *** .35 *** .39 ***
    Pain .58 *** .62 *** .65 ***
    Dyspnoea .40 *** .36 *** .40 ***
    Insomnia .47 *** .43 *** .49 ***
    Appetite loss .44 *** .44 *** .47 ***
    Constipation .31 *** .32 *** .34 ***
    Diarrhea .17 ** .10 ns .15 *
    Financial difficulties .39 *** .41 *** .43 ***
    Sum score -.68 *** -.69 *** -.73 ***
MFI-20
    General fatigue .58 *** .69 *** .68 ***
    Physical fatigue .61 *** .64 *** .67 ***
    Reduced activity .54 *** .63 *** .63 ***
    Reduced motivation .49 *** .61 *** .59 ***
    Mental fatigue .61 *** .65 *** .68 ***
    Fatigue sum score .65 *** .74 *** .75 ***

*: p<0.05

**: p<0.01

***: p<0.001; ns: Not significant.

Discussion

The first research question was whether the Amharic version of the HADS showed acceptable psychometric properties. The reliability was good with Cronbach’s α coefficients of 0.86/0.85/0.91 for the HADS anxiety subscale, depression subscale, and the total scale, respectively. These coefficients were even slightly higher than those of our German comparison sample (0.82/0.85/0.89) and in other studies performed in Mexico (0.79/0.80/0.86) [40], Chile (0.76/0.84/0.87) [41], Greece (0.83/0.84/0.88) [42], Australia (0.90/0.86/ 0.92) [43], and among Latina women in the US (0.85/0.83/0.88) [24].

All corrected item-test correlations were above 0.50 in the Ethiopian cancer patients’ sample, which means that each item positively contributed to the scale scores. Taken together, these reliability coefficients suggest the applicability of the Amharic version of the HADS for use in groups of cancer patients. However, the CFA coefficients of the Ethiopian sample were somewhat weaker than those of the German sample. Since the Ethiopian Cronbach α coefficients were nevertheless high, this means that the Ethiopian patients did not differentiate between the subscales anxiety and depression as sharply as the German patients did, an interpretation which is also supported by the high correlation (r = 0.75) between the anxiety and depression subscales.

***Measurement invariance between the Ethiopian and the German data set was established on a weak level (equal loadings) but not on the level of strong invariance (equal intercepts). One reason for this kind of differential item functioning was that the item D14 (“I can enjoy a good book or radio or TV program”) performed in different ways in Ethiopia and Germany. The loading of this item was sufficiently high (0.55) even in the Ethiopian sample, but the intercepts were different which means that fewer Ethiopian patients agreed that they enjoyed reading books and watching TV. This illustrates that the transfer of questionnaires from Western countries to low income countries may be problematic [44,45]. However, removing item D14 and calculating analyses with the remaining six items has the disadvantage that the results cannot be compared with those reported from other studies. Hence, we preferred to keep all of the scales.

The comparison between the Ethiopian and the German cancer patients showed that the Ethiopian patients were more anxious (d = 0.26) and more severely depressed (d = 0.84) than the German ones. The HADS mean scores of the Ethiopian cancer patients (7.9/9.3) for anxiety and depression, respectively, were also markedly higher than those obtained in other countries such as India (6.5/6.8) [46], Chile (3.9/6.2) [41], and Jordan (M = 6.3/7.9) [47], and the scores are also much higher than those obtained with the Amharic HADS version in Ethiopian HIV patients (4.0/4.0) [36]. Since normative HADS data from Ethiopia are not available, the question must remain open concerning the degree to which the differences between the Ethiopian cancer patients and cancer patients from other countries are due to the particular situation of cancer patients, and to what degree these mean score differences reflect general response tendencies in Ethiopia. Nevertheless, the high levels of mental psychological burden in the Ethiopian patients lead to the conclusion that there are unrecognized and unmet needs for psychosocial care.

Anxiety and depression were associated with tumor stage. Patients with stage 4 cancer had the highest depression scores. This was also observed in other studies performed in Ethiopia [11], Germany [28], Taiwan [48], Mexico [49], and several Southeast Asian countries [50], and can be considered an argument for the known-groups validity of the Amharic version of the HADS.

While the relationship between tumor stage and depression can easily be understood, it is interesting to see that patients who received medical treatment (surgery or chemotherapy) were significantly less anxious and less depressed than patients who did not get such treatment. This is also in line with other studies from low- and middle-income Southeast Asian countries, where patients who received surgery were less anxious and less depressed than those who did not. This relationship is less pronounced in studies performed in HICs. One possible reason is that in LICs, treatment is primarily focused on patients with a lower tumor stage, while patients with stage 4 cancer often do not get such treatment. Another possible reason might be that the fact of getting medical help and treatment itself (irrespective of the medical impact of such treatment) has a greater beneficial effect on the mental situation of patients in LICs countries than it does in HICs.

One finding was that there were differences between illiterate and literate people in their responses to the HADS. The percentage of illiterate patients (52.7%) in this study was comparable to that reported in other Ethiopian examinations: 43.9% [51], 68.6% [25], 69.0% [10], and 80.0% [8]. Although literacy rates are increasing, illiteracy remains a major problem in psycho-oncological research in Ethiopia. Nevertheless, our study showed that the research assistants were still able to get reliable data from illiterate patients. Although it took them a long time to interview the patients and fill in the questionnaire when the study first began, after gaining some experience with the procedure, the study assistants became familiar with the materials and could perform the study more effectively.

In the discussion of the measurement invariance between Ethiopia and Germany, we mentioned that item D14 (reading books/watching TV) strongly contributed to the differences. This item also showed the most pronounced difference between the illiterate and the literate patients within the Ethiopian sample (d = 0.79). However, in all of the other items the illiterate patients were more anxious and depressed than the literate ones. Since there were no significant differences between these groups in terms of cancer type and tumor stage, these differences cannot be due to these possible confounders. Further research is needed to investigate the impact of illiteracy on the responses to questionnaires and to interpret the items in the context of cultural differences [44,45,52].

Anxiety and depression were strongly correlated with all facets of QoL (except diarrhea) and fatigue (Table 7). Though the correlations with the Emotional functioning scale of the EORTC QLQ-C30 were among the highest coefficients, the associations with fatigue and with pain were of nearly equal magnitude. The high correlations underline the importance of anxiety and depression for the assessment of QoL.

Some limitations of this study should be mentioned. The Ethiopian patient sample was recruited in one hospital in Gondar; therefore, the generalizability to other Ethiopian or African areas is unclear. The sample size was sufficient for comparisons on the group level, but not large enough for comparisons among various cancer types with sufficient precision. The Ethiopian and German samples were matched for age and gender, but not for clinical variables. Due to the diversity of tumor localizations and the lack of tumor stage data in both samples, it was not possible to match after these clinical variables. This limits the comparability between both samples. The German sample (n = 1,664) was larger than the Ethiopian one (n = 256), however, this has an only marginal effect on the effect sizes for the comparison between Ethiopia and Germany. However, the differences in the distributions of the tumor stages can limit the comparability between the two samples. Because normative HADS data are not available for Ethiopia or Africa, it is difficult to estimate the level of burden due to the disease. The lack of strong measurement invariance for the comparison between Ethiopia and Germany limits the comparability of the mean scores obtained in these countries. Despite the problems with item D14, we do not recommend removing this item. A modified version omitting a problematic item would result in incomparability of the HADS results obtained in other examinations.

In conclusion, the Amharic version of the HADS provides reliable information on anxiety and depression. The high levels of mental burden in the Ethiopian cancer patients indicate unmet needs for psychosocial care.

Supporting information

S1 Data. HADS items.

(SAV)

Acknowledgments

We thank the patients, the study assistants who collected the data, and Mesfin Assefa who supervised the data collection.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Rosemary Frey

21 Jul 2020

PONE-D-20-01559

The Hospital Anxiety and Depression Scale (HADS) applied to Ethiopian cancer patients

PLOS ONE

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Reviewer #1: The study is very interesting in describing the HADS-results in Ethiopian cancer patients.

Unfortunately, there are many aspects which should be considered.

A major revision is necessary.

(see attachment)

Reviewer #2: This is an important study that will make useful contributions to existing knowledge in related fields, especially with regard to Ethiopia. Given the cross-cultural comparisons, it might have been more appropriate to have submitted this to the Journal of Cross-Cultural Psychology for publication. However in all other respects it appears to be sound and useful. The manuscript is clearly written and logically coherent, the alphas of the related scales are sufficient, and the measures used are appropriate and valid, as well as the added check of comparison across cultural contexts. One can imagine that the disparate sizes of the Ethiopian and German samples made comparisons more difficult because the threshold for achieving significance would be different in the two samples, but this is not prohibitive. The final discussion section should acknowledge this limitation to the study however.

A few very minor specific recommended corrections...

35 - was/were. 'Data' is plural, so should be 'Data were...'.

50 - Add 'Germany' to keywords.

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Decision Letter 1

Rosemary Frey

5 Oct 2020

PONE-D-20-01559R1

The Hospital Anxiety and Depression Scale (HADS) applied to Ethiopian cancer patients

PLOS ONE

Dear Dr. Hinz,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Please address the issues raised by Reviewer 1 concerning sample size differences.

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Please submit your revised manuscript by 5 November 2020. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Rosemary Frey

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for considering the comments.

Only two remaining aspects:

"... This limits the comparability between both samples. The German sample was larger than the Ethiopian one, however, this has an only marginal effect on the effect sizes for the comparison between Ethiopia and Germany. ..."

Please include the number of the german sample in the text and mention that the tumor stage was different in the Ethiopian versus the german sample (Stage I 7,8% versus 22,2%) which can influence the HADS results.

Reviewer #2: The sample size differences and other incomparable features between the two samples have now been acknowledged and discussed as study limitations in the concluding section, and in other respects the analysis seems adequate at this revised stage.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Dec 3;15(12):e0243357. doi: 10.1371/journal.pone.0243357.r004

Author response to Decision Letter 1


7 Oct 2020

Reviewer #1:

Please include the number of the german sample in the text and mention that the tumor stage was different in the Ethiopian versus the german sample (Stage I 7,8% versus 22,2%) which can influence the HADS results.

Response.

We already gave the number of the German sample in the methods section.

In the Limitations section we now repeated the number and acknowledged that the differences in the distributions of the tumor stages limit the comparability of the two samples.

Reviewer #2 had no additional remarks.

Attachment

Submitted filename: Response to Reviewers R2.docx

Decision Letter 2

Rosemary Frey

20 Nov 2020

The Hospital Anxiety and Depression Scale (HADS) applied to Ethiopian cancer patients

PONE-D-20-01559R2

Dear Dr. Hinz,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Rosemary Frey

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Acceptance letter

Rosemary Frey

24 Nov 2020

PONE-D-20-01559R2

The Hospital Anxiety and Depression Scale (HADS) applied to Ethiopian cancer patients

Dear Dr. Hinz:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Rosemary Frey

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Data. HADS items.

    (SAV)

    Attachment

    Submitted filename: Responses to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers R2.docx

    Data Availability Statement

    All relevant data are within the manuscript and its Supporting Information files.


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