Validity of the Memorial Symptom Assessment Scale-Short Form Psychological Subscales in Advanced Cancer Patients

Vol. 42 No. 5 November 2011 Journal of Pain and Symptom Management 761 Brief Methodological Report Validity of the Memorial Symptom Assessment Scale-Short Form Psychological Subscales in Advanced Cancer Patients Katherine Webber, MBBS, MRCP, and Andrew N. Davies, MBBS, MSc, MD, FRCP Royal Marsden NHS Hospitals Trust, London and Surrey, United Kingdom Abstract Context. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) is designed to evaluate physical and psychological symptom burden in advanced cancer patients. There are no current data assessing the validity of the MSAS-SF psychological symptom scores when compared with anxiety and depression. Objectives. This observational cross-sectional study was designed to determine the relationship between the MSAS-SF subscales and the presence of anxiety and depression. Methods. Advanced cancer patients attending a U.K. oncology center completed the MSAS-SF and the Hospital Anxiety and Depression Scale. Results. One hundred twenty patients participated in the study. There was an association between the presence of anxiety and depression and the MSAS-SF global distress index. There was no association between the presence of anxiety and depression and the MSAS-SF physical symptom subscale. The MSAS-SF psychological symptom subscale was more closely correlated with anxiety than depression. Conclusion. These results support the validity of the MSAS-SF global distress index and psychological subscales in the assessment of patients with anxiety and depressive disorders. J Pain Symptom Manage 2011;42:761e767. Ó 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Assessment tools, anxiety, depression, cancer, palliative, symptoms, psychological distress Introduction Assessment and quantification of physical and psychological symptoms is an integral part Address correspondence to: Katherine Webber, MBBS, MRCP, Department of Palliative Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. E-mail: kath.webber@ rmh.nhs.uk Accepted for publication: February 6, 2011. Ó 2011 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved. of everyday clinical practice for all health care professionals. It is essential to have standardized measures available to meaningfully compare symptom burden between individual patients and patient groups. Such measures are imperative to evaluate the effectiveness of clinical and therapeutic interventions on symptom burden and to identify the prevalence of different problems. To ensure that symptoms can be measured in a standardized way, it is necessary to have validated tools available. 0885-3924/$ - see front matter doi:10.1016/j.jpainsymman.2011.02.007

762 Webber and Davies Vol. 42 No. 5 November 2011 Validity defines how well a scale measures or correlates with the theorized construct that it purports to measure. Construct validity is most commonly used to assess a tool that measures health-related outcomes that are difficult to assess directly, and there is no single gold standard criterion. It is evaluated by comparing the scale with variables related to the construct or theoretical grounds for being related. The Memorial Symptom Assessment Scale (MSAS) was originally developed by Portenoy et al. 1 to assess and quantify a large range of physical and psychological symptoms in advanced cancer patients. It consists of 32 symptoms, and patients must rate the presence, frequency, and distress caused by each symptom. Chang et al. 2 subsequently developed and validated the MSAS-Short Form (MSAS-SF), which is a modified version of the MSAS designed to reduce patient burden. The MSAS-SF consists of the same 32 symptoms as the original MSAS but requires patients to rate the distress caused by 28 physical symptoms and frequency of four psychological symptoms. The original MSAS validation study identified three subscales within the tool that could be used to measure different parameters. 1 The global distress index (GDI) measures four psychological (feeling sad, worrying, feeling irritable, and feeling nervous) and six physical symptoms (lack of energy, pain, lack of appetite, feeling drowsy, constipation, and dry mouth). The physical symptom subscale (PHYS) distress score comprises 12 physical symptoms (lack of energy, pain, lack of appetite, feeling drowsy, constipation, dry mouth, nausea, vomiting, change in taste, weight loss, feeling bloated, and dizziness). The psychological symptom subscale (PSYCH) distress score includes six symptoms (worrying, feeling sad, feeling nervous, difficulty sleeping, feeling irritable, and difficulty concentrating). The MSAS-SF was initially validated in advanced cancer patients by assessing correlations between these subscales and the Functional Assessment of Cancer Therapy (FACT-G) tool that measures different aspects of quality of life. There were strong correlations between the MSAS-SF subscales and physical and emotional well-being on the FACT-G. There are no current data evaluating the correlation between psychological distress scores on the MSAS-SF and a diagnosis of anxiety or depression. Advanced cancer patients suffer from multiple symptoms, 3 and depressive disorders are reported as occurring in up to 50% of such patients. 4 Certain studies report a higher prevalence of physical symptoms in patients with a depressive illness; 5,6 however, other studies report no such association. 7,8 These studies have used different methods to screen for and diagnose depressive illness and to assess physical symptom burden; so differences in results are difficult to interpret. Most studies have used the Edmonton Symptom Assessment System 9 to quantify symptom burden. This is a well-validated tool 10,11 but evaluates only nine common symptoms. No previous study has attempted to examine the relationship between physical and psychological symptoms by using the MSAS-SF to quantify physical symptom burden. The aims of this study were the following: 1) to evaluate the construct validity of the MSAS-SF psychological subscales by assessing correlation with the Hospital Anxiety and Depression Scale (HADS) and 2) to determine if there is a relationship between physical symptoms on the MSAS-SF and the presence of anxiety or depression on the HADS. Methods Setting and Sample This study was conducted at a large U.K. cancer center. The cancer center consists of two hospitals and serves a population of 1.7 million in the southeast of England. Patients were eligible to participate if they had a diagnosis of incurable metastatic cancer, were older than 18 years of age, and were able to complete the study proforma. Recruitment occurred from the inpatient and outpatient departments. The Royal Marsden NHS Foundation Trust Committee for Clinical Research and Research Ethics Committee approved the study. Patients received a patient information sheet and had at least 24 hours to consider entry into the study. Written informed consent was obtained before participation. Recruitment occurred for four months, beginning May 1, 2008. Instruments The instruments were administered by a researcher in both the inpatient and the

Vol. 42 No. 5 November 2011 Validity of the MSAS-SF 763 outpatient departments. Participants were required to complete the MSAS-SF and the HADS. Demographic data also were collected from the electronic patient record. The MSAS-SF requires patients to rate the level of distress associated with 28 physical symptoms over the previous week on a fivepoint Likert scale (not at all, 0.8; a little bit, 1.6; somewhat, 2.4; quite a bit, 3.2; and very much, 4.0). Each response is allocated a score, and if the symptom is not present, a value of zero is assigned. The patient also must rate the frequency of psychological symptoms during the previous seven days on a four-point scale (rarely, 1; occasionally, 2; frequently, 3; almost constantly, 4). The HADS is a validated tool to screen for anxiety and depression in patients with medical illness. 12 It is validated in advanced cancer populations 13,14 and consists of seven questions relating to anxiety (HADS-A) and seven to depression (HADS-D). Each question has a possible four responses, and the score is determined on scales of 0e3; the most negative response receives the highest score. The maximum score for the anxiety and depression subscales is 21. A cutoff score of 11 or above on each subscale is used to screen positively for the presence of anxiety or depression. 12 Statistics Descriptive statistics were used to initially examine and present the data. The Mann- Whitney test was used to assess the correlation between the presence of anxiety and depression on the HADS and the MSAS-SF physical, psychological, and GDI scores. Pearson pairwise correlation coefficients were calculated between the MSAS-SF subscales and the total HADS score and the HADS subscales scores. Statistical analysis was performed using SPSS (SPSS, Inc., Chicago, IL). Results One hundred thirty-five patients were approached to participate in the study, and 15 patients refused. The reasons for refusal were fatigue (seven patients), no reason given (six patients), and not wanting to participate in research (two patients). Demographics One hundred twenty patients completed the study. The median age was 61 years (range 20e87 years), and 54% were female. Over onethird of patients (39%) had an Eastern Cooperative Oncology Group performance status score of three and above. The most common tumor group was gastrointestinal cancer (28%), followed by breast cancer (14%), lung cancer (13%), and urological cancer (13%) (Table 1). Prevalence of Physical Symptoms All patients were experiencing numerous physical symptoms according to the MSAS-SF; the median number of reported physical symptoms was 15 (range 4e27), with the most common reported symptoms being lack of energy (92%), feeling drowsy (88%), and pain (86%). The symptom reported to be the most distressing was pain (69% of patients experiencing this symptom rated distress level as quite a bit or very much), followed by constipation (61% rated distress level as quite a bit or very much) and then lack of energy (58%) (Table 2). Prevalence of Psychological Symptoms On the MSAS-SF, the most frequently reported psychological symptom was worrying Table 1 Demographic Data Characteristics Frequency (n ¼ 120) Age Median 61 yr (range 20e87 yr) Sex Female 65 (54%) Male 55 (46%) ECOG performance status 0 3 (2%) 1 32 (27%) 2 38 (32%) 3 43 (36%) 4 4 (3%) Cancer diagnosis Gastrointestinal 33 (28%) Breast 17 (14%) Lung 16 (13%) Urological 16 (13%) Hemato-oncological 12 (10%) Gynecological 10 (8%) Head and neck 8 (7%) Other 8 (7%) Smoking status Never smoked 49 (41%) Ex-smoker 50 (42%) Current smoker 21 (17%) ECOG ¼ Eastern Cooperative Oncology Group.

764 Webber and Davies Vol. 42 No. 5 November 2011 Table 2 MSAS-SF Physical Symptom Prevalence How Much Did It Distress You? Not at All/A Little Somewhat Quite a Bit/Very Much Physical Symptom n n % n % n % Lack of energy 110 25 23 21 19 64 58 Feeling drowsy 106 31 29 32 30 43 41 Pain 103 20 19 12 12 71 69 Dry mouth 84 37 44 16 19 31 37 Difficulty concentrating 83 38 46 19 23 26 31 Lack of appetite 83 26 31 13 16 44 53 Weight loss 77 34 44 10 13 33 43 Change in the way food tastes 74 32 43 16 22 26 35 Constipation 71 16 22 12 17 43 61 Nausea 70 19 27 17 24 34 49 (68%), followed by sadness (63%) and irritability (47%). Worrying was described as occurring almost constantly in 11% of patients experiencing it, but most patients that experienced the four psychological symptoms described them as occurring occasionally or frequently (Table 3). On the HADS-A, 18 patients (15%) screened positively for anxiety, and on the HADS-D, 30 patients (25%) screened positively for depression. Seven patients (6%) screened positively for both anxiety and depression. For the HADS-A, the mean score in all patients was 6.39, standard deviation (SD) 3.884, and range of scores 0e16. For the HADS-D, the mean score in all patients was 7.29, SD 4.473, and range of scores 0e20. Association Between MSAS-SF Subscales and HADS Patients who screened positively for anxiety (HADS-A $ 11) had a statistically significant higher score on the MSAS-SF psychological subscale (P ¼ 0.001) than those who screened negatively for anxiety. There was, however, no significant difference in MSAS-SF PSYCH scores between depressed (HADS-D $ 11) and nondepressed patients (P ¼ 0.1) (Table 4). The MSAS-SF psychological subscale was more strongly correlated with the HADS-A subscale (0.649) than the HADS total score (0.589) or the HADS-D subscale (0.35) (Table 5). Patients who screened positively for anxiety on the HADS-A ($11) had a statistically significant higher score than those who screened negatively for anxiety on the MSAS-SF total score (P ¼ 0.026) and the MSAS-SF GDI subscale (P ¼ 0.013). There was no significant difference between anxious and nonanxious patients on the MSAS-SF PHYS (P ¼ 0.431) (Table 4). Patients who screened positively for depression on the HADS-D ($11) had significantly higher scores than nondepressed patients on the MSAS-SF total score (P ¼ 0.009) and MSAS-SF GDI subscale (P ¼ 0.006) but not on the MSAS-SF PHYS (P ¼ 0.063) (Table 4). The MSAS-SF PHYS correlated poorly with all HADS scores (Table 5). The MSAS-SF GDI had a stronger correlation with the HADS-D than the MSAS-SF psychological subscale (0.411 compared with 0.35) (Table 5). Table 3 MSAS-SF Psychological Symptom Prevalence How Frequently Did You Experience It? Rarely Occasionally/Frequently Almost Constantly Psychological Symptom n n % n % n % Worrying 82 6 7 67 82 9 11 Sad 76 11 15 61 80 4 5 Irritable 57 5 9 48 84 4 7 Nervous 50 7 14 40 80 3 6

Vol. 42 No. 5 November 2011 Validity of the MSAS-SF 765 Table 4 Association Between MSAS-SF Subscales and HADS Anxiety and Depression Subscales HADS-A <11 (n ¼ 102) HADS-A $11 (n ¼ 18) Mann-Whitney (P-value) HADS-D <11 (n ¼ 90) HADS-D $11 (n ¼ 30) P-value MSAS-SF T 37 (14.8) 47.76 (18) 0.026 36.5 (15.6) 44.8 (14.7) 0.009 GDI 17.4 (6.4) 21.9 (6) 0.013 17.3 (6.6) 20.4 (5.7) 0.006 PHYS 20.2 (8.7) 22.4 (9.9) 0.431 19.8 (9) 22.9 (7.8) 0.063 PSYCH 7.37 (4.2) 10.9 (3.6) 0.001 7.5 (4.5) 9 (3.6) 0.1 HADS-A ¼ Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D ¼ Hospital Anxiety and Depression Scale-Depression subscale; MSAS-SF T ¼ Memorial Symptom Assessment Scale-Short Form Total Score; GDI ¼ Memorial Symptom Assessment Scale Global Distress Index; PHYS ¼ Memorial Symptom Assessment Scale Physical symptom subscale; PSYCH ¼ Memorial Symptom Assessment Scale Psychological symptom subscale. Discussion The most prevalent physical symptoms reported in this study were lack of energy (92%), feeling drowsy (88%), pain (86%), and dry mouth (70%). This is similar to the reported prevalence of physical symptoms in the literature 3 and emphasizes the high burden of problems experienced by advanced cancer patients. On the HADS-A, 15% of patients screened positively for anxiety, and on the HADS-D, 25% of patients screened positively for depression. Six percent of patients screened positively for both anxiety and depression on the HADS. The prevalence of depression in patients with advanced disease varies considerably across studies depending on the definition and methods used to determine the diagnosis. Even for a single questionnaire, such as the HADS, there are several ways of reporting prevalence using different cutoff values. Hotopf et al. 4 reported definite depression (HADS-D cutoff score of >10) rates from 16% to 50% in their systematic review of depression in patients with advanced disease. Our study reinforces that depression Table 5 Pearson Correlations Between MSAS-SF and HADS Subscales HADS-T HADS-A HADS-D MSAS-SF T 0.462 0.399 0.37 GDI 0.559 0.525 0.411 PHYS 0.296 0.172 0.31 PSYCH 0.589 0.649 0.35 P < 0.001 for all results. HADS-T ¼ Hospital Anxiety and Depression Scale Total Score; HADS-A ¼ Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-D ¼ Hospital Anxiety and Depression Scale-Depression subscale; GDI ¼ Memorial Symptom Assessment Scale Global Distress Index; PHYS ¼ Memorial Symptom Assessment Scale Physical symptom subscale; PSYCH ¼ Memorial Symptom Assessment Scale Psychological symptom subscale. and anxiety are common problems experienced by advanced cancer patients. It is interesting that the MSAS-SF PSYCH (four psychological symptoms: feeling sad, worrying, feeling irritable, and feeling nervous and two other symptoms: difficulty sleeping and difficulty concentrating) is more strongly correlated with anxiety than depression. These results imply that the psychological distress measured by the MSAS-SF is a separate construct from a depressive mood disorder and the presence of depression does not mean higher levels of distress from these psychological symptoms. The symptoms included in the MSAS-SF PSYCH are thus more representative of an anxiety disorder. The level of correlation between the MSAS-SF psychological subscale and the total HADS score implies that the two scales are measuring similar but not identical constructs, which supports the validity of the MSAS-SF PSYCH in the measurement of psychological problems. There was no relationship between the presence of a positive screening of anxiety or depression on the HADS subscales and the MSAS-SF PHYS, and there was generally a poor correlation between these two scales. The absence of an association between anxiety or depression and physical symptom burden in this study is supported by previous palliative care research where no relationship was found between the presence of anxiety and depression and common physical symptoms (pain, nausea, anorexia, and dyspnea). 6,7 The MSAS-SF GDI had a positive relationship with the presence of both anxiety and depression and was more closely correlated with the HADS-D than the MSAS-SF PSYCH. The additional physical symptoms in the GDI (lack of energy, pain, lack of appetite, feeling

766 Webber and Davies Vol. 42 No. 5 November 2011 drowsy, constipation, and dry mouth) are thus more common in depressed patients than the two physical symptoms in the PSYCH (difficulty sleeping and difficulty concentrating). Many physical symptoms experienced by advanced cancer patients are common in both advanced disease and depressive illness (lack of energy, drowsiness, and difficulty sleeping), and it is interesting that certain combinations of physical symptoms are more highly correlated to depression than others. It is possible that these symptoms result either from the depressive illness itself or as side effects from medication given to treat depression. In clinical practice, care must be taken to individually assess patients with multiple physical symptoms for anxiety and depressive disorders and treat accordingly. Study Limitations There are a number of limitations to this study. The patients were all recruited from a tertiary cancer center and, therefore, results may not be generalized to other advanced cancer populations. However, the symptom prevalence data and demographic mix are similar to other studies, adding value to the validity of our data. In this study, screening tools were used to detect symptom burden and depression and anxiety. Screening tools indicate the need for a more comprehensive assessment and are not diagnostic. There are recommended cutoff scores for the HADS based on previous studies comparing the tools with psychiatric diagnoses. 13e16 However, there will always be false positive and negative results despite using optimal cutoffs. In this study, we cannot comment on what proportion of positive screens represents true cases, only that results are based on patients with a higher likelihood of these disorders, using screening tests with acceptable sensitivity and specificity in previous studies. The burden of completing two questionnaires meant that there were few patients (3%) represented with an Eastern Cooperative Oncology Group performance status score of four (completely disabled or totally confined to bed or chair). Such patients were less likely to complete the study proforma because of the burden of their advanced disease (fatigue or delirium). The study data are, therefore, not representative of patients with such physical conditions; however, without using proxy assessment, it would not be possible to obtain such data from this group of patients. The sample size was a convenience sample of 120 patients and not formally calculated. It was based on similar studies validating tools and the number of patients that could feasibly be recruited in the time frame of the study. Disclosures and Acknowledgments The Royal Marsden Hospital Palliative Medicine Research Fund funded this study. The authors declare no conflicts of interest. The authors thank Yolanda Barbachano for statistical advice and Philippa Johnston for invaluable administrative support. References 1. Portenoy RK, Thaler HT, Kornblith AB, et al. The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer 1994;30A:1326e1336. 2. Chang VT, Hwang SS, Feuerman M, Kasimis BS, Thaler HT. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF). Cancer 2000;89: 1162e1171. 3. Teunissen S, Wesker W, Kruitwagen C, et al. Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manage 2007;34:94e104. 4. Hotopf M, Chidgey J, Addington-Hall J, Ly KL. Depression in advanced disease: a systematic review. Part 1. Prevalence and case finding. Palliat Med 2002;16:81e97. 5. Delgado-Guay M, Parsons H, Li Z, Palmer J, Bruera E. Symptom distress in advanced cancer patients with anxiety and depression in the palliative care setting. Support Care Cancer 2009;17: 573e579. 6. Teunissen SC, de Graeff A, Voest EE, de Haes JC. Are anxiety and depressed mood related to physical symptom burden? A study in hospitalized advanced cancer patients. Palliat Med 2007;21: 341e346. 7. Lloyd-Williams M, Dennis M, Taylor F. A prospective study to determine the association between physical symptoms and depression in patients with advanced cancer. Palliat Med 2004;18: 558e563.

Vol. 42 No. 5 November 2011 Validity of the MSAS-SF 767 8. Chen ML, Chang HK. Physical symptom profiles of depressed and nondepressed patients with cancer. Palliat Med 2004;18:712e718. 9. Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K. The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients. J Palliat Care 1991;7:6e9. 10. Chang VT, Hwang SS, Feuerman M. Validation of the Edmonton Symptom Assessment Scale. Cancer 2000;88:2164e2171. 11. Nekolaichuk C, Watanabe S, Beaumont C. The Edmonton Symptom Assessment System: a 15-year retrospective review of validation studies (1991e2006). Palliat Med 2008;22:111e122. 12. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983; 67:361e370. 13. Lloyd-Williams M, Friedman T, Rudd N. An analysis of the validity of the Hospital Anxiety and Depression Scale as a screening tool in patients with advanced metastatic cancer. J Pain Symptom Manage 2001;22:990e996. 14. Le Fevre P, Devereux J, Smith S, Lawrie SM, Cornbleet M. Screening for psychiatric illness in the palliative care inpatient setting: a comparison between the Hospital Anxiety and Depression Scale and the General Health Questionnaire-12. Palliat Med 1999;13:399e407. 15. Ibbotson T, Maguire P, Selby P, Priestman T, Wallace L. Screening for anxiety and depression in cancer patients: the effects of disease and treatment. Eur J Cancer 1994;30A:37e40. 16. Singer S, Kuhnt S, Gotze H, et al. Hospital Anxiety and Depression Scale cutoff scores for cancer patients in acute care. Br J Cancer 2009;100:908e912.