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Measuring disability and quality of life in established rheumatoid arthritis
Best Practice & Research Clinical Rheumatology Vol. 21, No. 5, pp. 827–840, 2007 doi:10.1016/j.berh.2007.05.004 available online at http://www.sciencedirect.com
2 Measuring disability and quality of life in established rheumatoid arthritis Siri Lillegraven
MD
Research Fellow Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
Tore K. Kvien *
MD, PhD
Professor Department of Rheumatology, Diakonhjemmet Hospital and Faculty of Medicine, University of Oslo, Norway
Rheumatoid arthritis is a chronic inflammatory disease with a major impact on physical and psychological health. It can cause severe disability and reduce health-related quality of life, aspects that are important to patients. Thus, it is important to measure disability and healthrelated quality of life in clinical practice and in clinical trials. This article presents an overview of the most important measures of outcome concerning disability and health-related quality of life, including different forms of the Health Assessment Questionnaire (HAQ, MHAQ, MDHAQ, HAQ II), visual analogue scales for fatigue and function, SF-36, Arthritis Impact Measurement Scales (AIMS/AIMS2), the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire, Nottingham Health Profile, Sickness Impact Profile and the utility instruments 15D, EQ-5D, SF-6D and Health Utilities Index (HUI) 2 and 3. Key words: disability; health-related quality of life; rheumatoid arthritis; utility.
INTRODUCTION Rheumatoid arthritis (RA) is a common autoimmune disease that has articular and extra-articular manifestations.1 It has a prevalence of approximately 0.5–1% and is most prevalent in women, with a 2.5/1 ratio between women and men.1 RA can have a major impact on health-related quality of life (HRQoL).2 The aim of this chapter
* Corresponding author. Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, N-0319 Oslo, Norway. Tel.: þ47 22 45 17 50; Fax: þ47 22 45 17 78. E-mail address: [email protected] (T.K. Kvien). 1521-6942/$ - see front matter ª 2007 Elsevier Ltd. All rights reserved.
828 S. Lillegraven and T. K. Kvien
is to present an overview of different instruments that are used to assess disability and HRQoL in patients with RA. What is disability? Several definitions of the word disability have been presented. In a recent review, Leonardi et al3 propose the following: Disability is a difficulty in functioning at the body, person or societal levels, in one or more life domains, as experienced by an individual with a health condition in interaction with contextual factors. Whereas impairment represents disturbances at the organ level caused by a pathological process; disability reflects the consequences of impairment in terms of functional performance. What is health-related quality of life? HRQoL is a broad concept that can be defined as the impact of health on an individual’s ability to function and on the perceived well-being in physical, mental and social domains of life.4 An important part of HRQoL is that it includes a patient’s satisfaction or response to his or her health status and limitations.5,6 The same disease state or limitation can thus affect HRQoL differently across patients, depending on personal factors. The difference between generic and disease-specific instruments Generic instruments are developed for use in patients regardless of disease. One of the major advantages of such instruments is the opportunity to compare results between disease groups, and so to cover a broad variety of disease-related factors. The disadvantages are that generic instruments might lack aspects that can be important in some diseases but not others; they can also be less sensitive to change.6 The disease-specific instruments described in the following sections have been developed for use in patients with RA or other arthritic diseases. Their advantage is that they aim to cover all the important factors in these conditions - exemplified by dexterity in RA – that is, components that might be less important in tools assessing a wider spectrum of diseases. The disadvantage of any disease-specific measure is that the results obtained cannot be compared with results from patient groups with other diagnoses. INSTRUMENTS MEASURING DISABILITY Generic measures SF-36 physical functioning The well-known generic health profile the Short Form 36 Health Questionnaire (SF-36) contains a domain concerning physical functioning. This is based on 10 items regarding limitations in physical activities because of health problems.7 This scale can be used as a measure of physical disability. However, none of the items directly addresses dexterity, which is important in RA.
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Other Other generic health profiles (the Sickness Impact Profile, the Nottingham Health Profile) also have items that capture physical limitations and can be used as measures of disability. Disease-specific measures The Stanford health assessment questionnaire The Stanford Health Assessment Questionnaire (HAQ)8,9 was introduced in the 1980s and is now widely used in evaluation of patients with RA. It was initially developed for use in rheumatology, but has also been applied to other diseases. Some investigators will therefore argue that HAQ can be considered a generic instrument. The original, but less used, full HAQ version contains questions concerning five dimensions – disability, economic costs, pain/discomfort, adverse effects of medication, and death – i.e. the original 5Ds for patient outcomes: disability, dollars, discomfort, doctor (iatrogenic consequences), and death. The disability index of the instrument includes questions about the ability of patients to perform 20 activities of daily living, and is most commonly referred to as the HAQ questionnaire, and sometimes as the HAQ disability index (HAQ-DI). Four response categories are available for each question: without any difficulty (score 0), with some difficulty (score 1), with much difficulty (score 2) or unable to do (score 3). The 20 activities are classified into eight categories with two or three activities each. A score is then assigned to each of the eight categories based on the highest score of the items within the category. Patients are also asked about use of aids and devices, and if they need help from another person for activities in any of the eight categories. If category score is lower than 2, it is increased to 2 within any category in which the patient uses a device or help from another person, so that the underlying disability is more accurately represented. It is important to note that HAQ scores without this adjustment will be lower than the scores obtained with the original scoring system. The total HAQ score, with range 0–3, is the mean of the scores for the eight categories.9 MHAQ, MDHAQ and HAQII The Modified Health Assessment Questionnaire (MHAQ)10,11, a modification of the HAQ, keeps one question from each of the eight categories in the HAQ and reduces the number of items to eight. No adjustment of scores is possible. The total MHAQ score is the mean of the scores for each activity. MHAQ can easily be administered in clinical practice but will provide lower scores than HAQ, especially for patients with high disease activity.10 A multidimensional health assessment questionnaire (MDHAQ) has been developed by Pincus et al12 and includes more items, such as demanding physical activities, pain, fatigue, anxiety and depression. The aim of the instrument is to be able to measure disability in patients with healthier conditions and avoid the ceiling effect of HAQ and MHAQ in patients with limited disability. Further, the MDHAQ was developed as a comprehensive measure of disability in a short and user-friendly format and also included questions on other dimensions of health, including stress, anxiety and depression. The same group has developed another revised HAQ – the HAQ II – that only includes 10 items.13 It has been reported to be at least as reliable and valid as HAQ and easier to administer because of the reduced number of questions.13,14
830 S. Lillegraven and T. K. Kvien
To summarize, it is important to remember that several HAQ instruments exist, and that these yield scores that cannot be compared directly. VAS-function A visual analogue scale (VAS) for function has been proposed by Wolfe et al.15 The aim is that this patient-weighted functional assessment scale complements multi-item scales. The VAS-function (VAS-F) yields more high values and fewer low values than the HAQ and HAQ-II.15 It is well correlated to other VAS scales, such as VAS-fatigue and VAS-pain. Further studies are needed to examine if this instrument have potential in clinical practice and research. Performance-based measures Grip strength, walking time, and button test Grip strength, walking time, and button test (rheumatology function tests; RFTs) were formerly used in clinical trials.16 These measures of physical function have been shown to predict later function and mortality, and identify work status.16 Grip strength has also been shown to be associated with radiological damage.17 In more recent years, RFTs have mostly been replaced by questionnaires, but some advocate that they now are underused.16 INSTRUMENTS MEASURING HEALTH-RELATED QUALITY OF LIFE Two main groups of instruments measure HRQoL: profiles and utility instruments. A profile contains separate scores for several dimensions. A utility score provides only one sum score for each patient on a scale from 0.0 (a health state similar to death) and 1.0 (perfect HRQoL). Some of the instruments also allow values below 0.0, representing health states that are considered worse than death. Generic measures: profiles SF-36 The SF-36 is the most widely used generic health status measure.7 It is used in health surveys in the general population as well as in various disease populations. The 36 items in the questionnaire are grouped into eight multi-item subscales measuring physical functioning (10 items), role limitations due to physical health (4 items), bodily pain (2 items), general health (5 items), vitality/energy/fatigue (4 items), social functioning (2 items), role limitations due to emotional problems (3 items) and mental health (5 items), plus one item on reported health transition. Each scale is expressed with values from 0 to 100 and a low score indicates poor health. A utility score, the SF-6D, can be computed from SF-36.18 The SF-36 scores correlate to a variety of disease-specific measures in RA.19 One particular advantage of SF-36 is that it also includes a scale on energy/vitality, a dimension that is considered important by patients but which is not included in the core set of outcomes for clinical trials. The SF-36 is a generic measure, meaning that its concepts are not specific to any age, disease or treatment group. This allows for comparisons of the relative burdens of different diseases and benefits of different treatments. It is suitable for
Measuring disability and quality of life in established RA 831
self-administration and performs similarly to disease-specific measures in RA.20 Table 1 shows SF-36 data from the Oslo RA register,21 as well as data for other of the instruments presented here. Nottingham health profile The Nottingham Health Profile (NHP) is a generic profile and has also been used in RA to some extent.22,23 This instrument contains 38 statements in six dimensions: physical mobility, pain, sleep, emotional reaction, social isolation and energy. The respondent is requested to answer ‘yes’ or ‘no’ to each statement. The scores for the dimension range from 0 (no problems or absence of limitations) to 100 (all potential problems are present). The disadvantage of NHP is that it requests the responder to answer ‘yes’ or ‘no’ to negative statements about health. The advantage of NHP is that it includes sleep and energy as dimensions – both considered important by patients. Sickness impact profile The Sickness Impact Profile (SIP) is a generic profile developed in the 1970s24, and has been less used in rheumatology than the other profiles presented. It comprises 189 items in 14 categories, covering a wide range of behavioral aspects related to sickness. Table 2 includes an overview of the different profiles, including SIP. Generic measures: utility instruments EQ-5D The EQ-5D25,26 captures five health dimensions (mobility, self-care, usual activity, pain/ discomfort and anxiety/depression), with three response categories within each of these dimensions; no problems, some or moderate problems and extreme problems.26 The EQ-5D encompasses 243 different health states and is one of the most widely used utility instruments in medicine.27 One reason for the widespread use may be that EQ-5D is easy to use with only five questions. SF-6D The SF-6D is a relatively new utility instrument in which some of the answers from SF-36 and SF-12 can be recalculated into a utility score.18 It contains six dimensions (physical functioning, role limitations, social functioning, pain, mental health, vitality), each with four to six levels. The opportunity to recalculate answers from SF-36, which is already measured in many clinical trails, makes it possible to reduce the amount of questionnaires in studies. 15D The Finnish 15D captures information from 15 dimensions (mobility, vision, hearing, breathing, sleep, eating, speech, bladder/bowel function, usual activities, mental function, discomfort/pain, depression, distress, vitality and sexual activity)28, with five response categories within each dimension; altogether, 515 health states can be described. It has a simple additive structure, where each of the dimensions has been validated into a certain value.
All patients (n ¼ 1041)
Women (n ¼ 813)
Men (n ¼ 228)
Age < 40 (n ¼ 97)
Age 40-59 years (n ¼ 341)
Age 60-74 years (n ¼ 373)
Age 75 years (n ¼ 230)
HAQ versions MHAQ HAQ
1.58 (0.54) 1.06 (0.75)
1.60 (0.55) 1.13 (0.74)
1.48 (0.50) 0.79 (0.71)
1.31 (0.40) 0.59 (0.57)
1.52 (0.50) 0.90 (0.67)
1.57 (0.51) 1.08 (0.70)
1.79 (0.64) 1.46 (0.81)
AIMS2 dimensions Mobility Walking and bending Hand/finger function Arm function Self-care Household tasks Social activity Support Pain Work Tension Mood
1.88 4.22 2.95 1.65 0.77 1.51 5.37 2.65 4.76 2.22 3.61 2.63
(2.25) (2.76) (2.52) (2.07) (1.71) (2.08) (1.45) (2.22) (2.53) (2.44) (1.95) (1.80)
2.05 4.30 3.20 1.77 0.81 1.63 5.35 2.73 4.86 2.27 3.68 2.67
(2.30) (2.73) (2.52) (2.12) (1.77) (2.13) (1.47) (2.24) (2.51) (2.49) (1.98) (1.83)
1.30 3.93 2.08 1.19 0.63 1.09 5.44 2.35 4.39 2.06 3.37 2.47
(1.99) (2.84) (2.32) (1.79) (1.47) (1.85) (1.35) (2.16) (2.60) (2.30) (1.83) (1.72)
0.88 2.54 1.71 0.69 0.33 0.65 4.91 2.46 3.79 2.08 3.31 2.10
(1.50) (2.32) (1.81) (1.34) (0.94) (1.20) (1.29) (2.04) (2.32) (2.50) (1.70) (1.50)
1.40 3.60 2.81 1.38 0.53 1.22 5.31 2.70 4.61 2.07 3.73 2.43
(1.84) (2.56) (2.40) (1.80) (1.35) (1.75) (1.44) (2.00) (2.60) (2.36) (1.97) (1.77)
1.79 4.41 2.99 1.67 0.68 1.39 5.31 2.78 4.75 2.22 3.56 2.61
(2.09) (2.57) (2.45) (2.08) (1.66) (1.89) (1.41) (2.32) (2.47) (2.44) (2.01) (1.76)
3.25 5.59 3.65 2.44 1.49 2.55 5.75 2.41 5.41 4.06 3.67 3.21
(2.74) (2.87) (2.81) (2.40) (2.25) (2.69) (1.50) (2.46) (2.47) (2.38) (1.91) (1.91)
SF-36 dimensions Physical functioning Role limitations physical Pain General health Vitality Social functioning Role limitations mental Mental health
52.5 32.4 43.9 47.5 42.0 69.4 56.9 70.2
(26.7) (37.9) (20.5) (22.5) (21.2) (27.2) (41.7) (19.7)
50.3 30.5 42.6 46.9 40.6 68.1 56.1 69.5
(26.6) (36.8) (20.1) (22.4) (21.0) (27.5) (41.7) (19.7)
60.1 39.5 48.5 49.5 47.2 74.1 59.5 72.9
(25.7) (40.9) (21.4) (22.8) (21.3) (25.7) (41.7) (19.3)
73.0 52.6 52.2 55.1 47.8 77.8 79.0 75.0
(22.8) (40.3) (20.9) (23.3) (20.9) (25.2) (35.1) (16.2)
58.8 41.3 45.6 49.5 42.4 72.1 65.5 71.7
(25.1) (39.9) (20.0) (23.2) (21.5) (26.4) (41.2) (19.5)
50.5 28.1 43.6 46.3 42.8 70.4 55.6 70.5
(24.3) (35.2) (19.6) (21.9) (20.6) (25.6) (40.6) (19.9)
37.1 16.9 38.5 43.2 37.6 60.0 35.4 65.4
(25.7) (29.8) (21.2) (21.0) (21.1) (29.4) (37.7) (20.0)
832 S. Lillegraven and T. K. Kvien
Table 1. Mean (SD) values for HAQ, MHAQ, AIMS2, SF-36, VAS-fatigue, EQ-VAS, 15D, SF-6D and EQ-5D.
VAS scales Fatigue EQ-VAS
46.6 (29.6) 62.0 (20.9)
48.9 (29.5) 61.6 (20.5)
38.2 (28.3) 63.3 (22.1)
39.5 (31.1) 70.0 (20.4)
46.1 (30.4) 64.7 (20.4)
45.9 (28.6) 61.8 (20.0)
51.7 (28.4) 54.5 (21.2)
Utility scores 15D SF-6D EQ-5D
0.81 (0.11) 0.64 (0.13) 0.60 (0.28)
0.81 (0.11) 0.63 (0.13) 0.60 (0.27)
0.82 (0.11) 0.67 (0.14) 0.63 (0.28)
0.88 (0.09) 0.71 (0.13) 0.68 (0.25)
0.83 (0.11) 0.66 (0.13) 0.62 (0.28)
0.81 (0.10) 0.64 (0.12) 0.61 (0.26)
0.76 (0.11) 0.59 (0.13) 0.55 (0.30)
Data from the Oslo RA register (ORAR). Approximately 85% of RA patients in the area of Oslo are included in ORAR,21 and 1041 (58.1%) of these patients responded to a questionnaire in 2004. AIMS, Arthritis Impact Measurement Scales; HAQ, Health Assessment Questionnaires; SF-36, Short Form 36 dimensions; VAS, visual analogue scale.
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834 S. Lillegraven and T. K. Kvien
Table 2. Dimensions of the different generic and disease-specific health profiles. Some similar dimensions have been placed under one heading. Dimensions
Pain Physical Hand / finger /arm function Mobility Household tasks Self-care Activities of daily living Social Social interaction/function Support Work Mental health Emotions Mood Level of tension
Generic profiles NHP
SF-36
SIP
AIMS
AIMS2
RAQoL
Role Physical, emotional Sexuality Other Energy/fatigue Physical contact Sleep Eating Communication General health Recreation and pastimes
Disease-specific profiles
AIMS, Arthritis Impact Measurement Scales; NHP, Nottingham Health Profile; RAQoL, Rheumatoid Arthritis Quality of Life questionnaire; SF-36, Short Form 36 dimensions; SIP, Sickness Impact Profile.
Health utilities index mark 2 and 3 The Health Utilities Index Mark 2 and Mark 3 (HUI2 and HUI3) include a profile and a utility instrument, together describing nearly 1 million health states.29 HUI3 should be the primary choice, whereas HUI2 includes self-care and fertility items. The HUI system, consisting of both HUI2 and HUI3, has been shown to be valid and have a minimal clinically important difference of about 0.03.29 Table 3 shows the properties of the utility instruments presented here. Other generic instruments VAS-fatigue Fatigue is frequently reported as a major factor for reduced quality of life30 by patients with RA. On the VAS-fatigue, the patient is asked to place his or her level of fatigue on
Measuring disability and quality of life in established RA 835
Table 3. Properties of the utility instruments 15D, EQ-5D, SF-6D, HUI2 and HUI3. Utility instrument 15D EQ-5D SF-6D HUI2 HUI3
Potential range
Dimensions
Response categories for each dimension
0.00e1.00 0.59e1.00 0.29e1.00 0.03e1.00 0.36e1.00
15 5 6 7 8
5 3 4e6 3e5 5e6
a scale. The mark is converted into a score between 0 and 100, 0 being absence of fatigue and 100 being major problems with fatigue. Comparative studies have revealed that the VAS-fatigue performs as well or better than more extensive fatigue instruments.31 Thus, VAS-fatigue might be a suitable instrument for use in clinical practice and trials, but it has not yet come into widely use. EQ-VAS EQ-VAS26 is a VAS that asks patients to place their own health on a scale from 0 (worst possible health) to 100 (best possible health). The EuroQol group25 developed this scale, and sometimes the combination of EQ-5D and EQ-VAS is called the EuroQol instrument. The EQ-VAS is not a true utility instrument. In the validation of utility instruments, patients are asked to sacrifice something (money, life years). When patients are asked to mark their HRQoL on a VAS scale, no such sacrifice is necessary. Thus, the score will on an average be lower. Disease-specific profiles The arthritis impact measurement scales The Arthritis Impact Measurement Scales (AIMS) was developed in 1980 to measure the health status of patients with arthritis32,33with seven demographic items and 55 health status items. It was later revised into the AIMS2, which is now mostly used. The arthritis impact measurement scales 2 The AIMS234 is an expanded and revised version of AIMS. It is a multidimensional disease-specific instrument with 78 items capturing information in 12 areas of health (mobility level, walking and bending, hand and finger function, arm function, self-care tasks, household tasks, social activity, support from family and friends, pain, work, level of tension, mood). These 12 scales can be aggregated into five major dimensions (physical functioning, social interaction, pain, work and affect). The score is from 0 to 10 (10 being worst possible health). AIMS2 also includes a separate question that addresses the patients’ priorities for improvement in health. The patients are asked to check three of 12 areas where they would most like to see improvement. A short form of AIMS2 (SF-AIMS2) has been validated in both French35 and Norwegian36 patient populations and seems to perform well.
836 S. Lillegraven and T. K. Kvien
The rheumatoid arthritis quality of life questionnaire The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is an RA-specific quality of life measure that comprises 30 statements about unfulfilled needs related to activities relevant to patients.37,38 Each question is answered with ‘yes’ or ‘no’. Possible scores range from 0 to 30, the higher score representing worse quality of life. RAQoL is quick for the patients to complete, valid and has been examined in the Dutch37,39, British37 and the Swedish populations.40
Practice points Questionnaires assessing health have been shown to be useful and important in clinical trials. HAQ has been shown to be the most important predictor of mortality, followed by other patient self-reported variables.41 These instruments were better predictors than radiographics, laboratory findings, and clinical examination. The choice of instrument should be based on the situation and the goals of the use. Is the setting a clinical trial or is the goal to evaluate the effect of interventions outside a trial? Instruments that have been validated should be chosen to optimize the results. Within a study setting, it is usually recommended to use instruments that have been used in similar studies, to facilitate comparisons between studies. Performance-based measures are currently less used than before but have been shown to be reproducible and reliable measures and predictors of later function and premature death in patients with RA, and can be especially suitable for clinical trials of longer duration (> 5 years).16
Research agenda Several utility instruments have been examined and used in RA42–47,with differing results. At the present time, there is no consensus regarding choice of utility instrument. Clearly, the choice of instrument will affect both the results of future studies of new biologic agents and their cost-effectiveness.48 Studies and recommendations are needed to decide which instrument is best suited for drug trials. Patients should be more strongly involved in the identification of important patient-reported outcomes reflecting disability and health-related quality of life.49,50 In particular, outcome measures of dimensions not included in current profiles should be validated and tested according to accepted criteria and procedures.51 Examples of such dimensions are sleep, fatigue, and well-being.49,50
Measuring disability and quality of life in established RA 837
Currently used measures focus on patient perceptions of quality of life. However, patient priorities/perceptions of importance and relevance are usually not included. Some studies have indicated that a focus on patient priorities might give additional information.52,53 The issue of patient priorities for improvement in combination with measures of perception require further attention on the research agenda. Core measures of disease activity include measures of pain, disability and patient global (ACR core set), whereas the composite disease activity measures DAS-28, CDAI and SDAI include only patient global assessment of disease activity. Wolfe et al have proposed a composite disease activity score, the Patient Activity Scale (PAS) based on pain, disability and patient global score.54 Further studies should be performed to establish a composite score based on patient-reported measures of dimensions of relevance to them, i.e. dimension identified on the basis of the perceived impact of RA. Patients can complete questionnaires in any setting that is independent from the health care setting. Thus, patient-reported measures can be completed frequently at home. Electronic tools for capturing information have a major potential for the future, via the internet55, computers in the hospital56 or personal digital assistants (PDA).57,58 Current research indicates that electronic versions of questionnaires addressing health-related quality of life in patients with RA perform similarly to a regular pencil/pen version. Measurements of health-related quality of life perform well regarding validity and responsiveness on a group level. However, studies addressing repeated measures of patient reports have shown great day-to-day variability.58,59 These findings indicate that a change in patient-reported measures also has to exceed the measurement errors to be a true improvement or deterioration. Such levels for HAQ have, for example, been shown to be around 0.4 on a scale from 0.0 to 3.0.59,60
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838 S. Lillegraven and T. K. Kvien 10. Uhlig T, Haavardsholm EA & Kvien TK. Comparison of the Health Assessment Questionnaire (HAQ) and the modified HAQ (MHAQ) in patients with rheumatoid arthritis. Rheumatology (Oxford) 2006; 45: 454–458. *11. Pincus T, Summey JA, Soraci Jr. SA et al. Assessment of patient satisfaction in activities of daily living using a modified Stanford Health Assessment Questionnaire. Arthritis and Rheumatism 1983; 26: 1346–1353. *12. Pincus T, Swearingen C & Wolfe F. Toward a multidimensional Health Assessment Questionnaire (MDHAQ): assessment of advanced activities of daily living and psychological status in the patientfriendly health assessment questionnaire format. Arthritis and Rheumatism 1999; 42: 2220–2230. 13. Wolfe F, Michaud K & Pincus T. Development and validation of the health assessment questionnaire II: a revised version of the health assessment questionnaire. Arthritis and Rheumatism 2004; 50: 3296–3305. 14. Wolfe F. Why the HAQ-II can be an effective substitute for the HAQ. Clinical and Experimental Rheumatology 2005; 23: S29–S30. 15. Wolfe F, Michaud K & Pincus T. Preliminary evaluation of a visual analog function scale for use in rheumatoid arthritis. The Journal of Rheumatology 2005; 32: 1261–1266. 16. Pincus T. Rheumatology function tests: quantitative physical measures to monitor morbidity and predict mortality in patients with rheumatic diseases. Clinical and Experimental Rheumatology 2005; 23: S85–S89. 17. Odegard S, Landewe R, van der HD et al. Association of early radiographic damage with impaired physical function in rheumatoid arthritis: a ten-year, longitudinal observational study in 238 patients. Arthritis and Rheumatism 2006; 54: 68–75. *18. Brazier J, Roberts J & Deverill M. The estimation of a preference-based measure of health from the SF-36. Journal of Health Economics 2002; 21: 271–292. 19. Birrell FN, Hassell AB, Jones PW & Dawes PT. How does the short form 36 health questionnaire (SF36) in rheumatoid arthritis (RA) relate to RA outcome measures and SF-36 population values? A crosssectional study. Clinical Rheumatology 2000; 19: 195–199. 20. Kvien TK, Kaasa S & Smedstad LM. Performance of the Norwegian SF-36 Health Survey in patients with rheumatoid arthritis. II. A comparison of the SF-36 with disease-specific measures. Journal of Clinical Epidemiology 1998; 51: 1077–1086. 21. Kvien TK & Uhlig T. The Oslo experience with arthritis registries. Clinical and Experimental Rheumatology 2003; 21: S118–S122. *22. Houssien DA, McKenna SP & Scott DL. The Nottingham Health Profile as a measure of disease activity and outcome in rheumatoid arthritis. British Journal of Rheumatology 1997; 36: 69–73. 23. Hunt SM, McEwen J & McKenna SP. Measuring health status: a new tool for clinicians and epidemiologists. The Journal of the Royal College of General Practitioners 1985; 35: 185–188. 24. Bergner M, Bobbitt RA, Pollard WE et al. The sickness impact profile: validation of a health status measure. Medical Care 1976; 14: 57–67. 25. EuroQol–a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy 1990; 16: 199–208. *26. Brooks R. EuroQol: the current state of play. Health Policy 1996; 37: 53–72. 27. Rasanen P, Roine E, Sintonen H et al. Use of quality-adjusted life years for the estimation of effectiveness of health care: A systematic literature review. International Journal of Technology Assessment in Health Care 2006; 22: 235–241. 28. Sintonen H. The 15D instrument of health-related quality of life: properties and applications. Annals of Medicine 2001; 33: 328–336. 29. Horsman J, Furlong W, Feeny D & Torrance G. The Health Utilities Index (HUI(R)): concepts, measurement properties and applications. Health and Quality of Life Outcomes 2003; 1: 54. 30. Hewlett S, Carr M, Ryan S et al. Outcomes generated by patients with rheumatoid arthritis: how important are they? Musculoskeletal care 2005; 3: 131–142. *31. Wolfe F. Fatigue assessments in rheumatoid arthritis: comparative performance of visual analog scales and longer fatigue questionnaires in 7760 patients. The Journal of Rheumatology 2004; 31: 1896–1902. 32. Meenan RF, Gertman PM & Mason JH. Measuring health status in arthritis. The arthritis impact measurement scales. Arthritis and Rheumatism 1980; 23: 146–152.
Measuring disability and quality of life in established RA 839 33. Mason JH, Anderson JJ & Meenan RF. A model of health status for rheumatoid arthritis. A factor analysis of the Arthritis Impact Measurement Scales. Arthritis and Rheumatism 1988; 31: 714–720. *34. Meenan RF, Mason JH, Anderson JJ et al. AIMS2. The content and properties of a revised and expanded Arthritis Impact Measurement Scales Health Status Questionnaire. Arthritis and Rheumatism 1992; 35: 1–10. 35. Guillemin F, Coste J, Pouchot J et al. The AIMS2-SF: a short form of the Arthritis Impact Measurement Scales 2. French Quality of Life in Rheumatology Group. Arthritis and Rheumatism 1997; 40: 1267–1274. 36. Haavardsholm EA, Kvien TK, Uhlig T et al. A comparison of agreement and sensitivity to change between AIMS2 and a short form of AIMS2 (AIMS2-SF) in more than 1,000 rheumatoid arthritis patients. The Journal of Rheumatology 2000; 27: 2810–2816. 37. de Jong Z, van der Heijde D, McKenna SP & Whalley D. The reliability and construct validity of the RAQoL: a rheumatoid arthritis-specific quality of life instrument. British Journal of Rheumatology 1997; 36: 878–883. 38. Whalley D, McKenna SP, de Jong Z & van der Heijde D. Quality of life in rheumatoid arthritis. British Journal of Rheumatology 1997; 36: 884–888. 39. Tijhuis GJ, de Jong Z, Zwinderman AH et al. The validity of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire. Rheumatology (Oxford) 2001; 40: 1112–1119. 40. Eberhardt K, Duckberg S, Larsson BM et al. Measuring health related quality of life in patients with rheumatoid arthritis–reliability, validity, and responsiveness of a Swedish version of RAQoL. Scandinavian Journal of Rheumatology 2002; 31: 6–12. 41. Wolfe F, Michaud K, Gefeller O & Choi HK. Predicting mortality in patients with rheumatoid arthritis. Arthritis and Rheumatism 2003; 48: 1530–1542. 42. Marra CA, Rashidi AA, Guh D et al. Are indirect utility measures reliable and responsive in rheumatoid arthritis patients? Quality of Life Research 2005; 14: 1333–1344. 43. Marra CA, Woolcott JC, Kopec JA et al. A comparison of generic, indirect utility measures (the HUI2, HUI3, SF-6D, and the EQ-5D) and disease-specific instruments (the RAQoL and the HAQ) in rheumatoid arthritis. Social Science & Medicine 2005; 60: 1571–1582. 44. Marra CA, Esdaile JM, Guh D et al. A comparison of four indirect methods of assessing utility values in rheumatoid arthritis. Medical Care 2004; 42: 1125–1131. 45. Kaplan RM, Groessl EJ, Sengupta N et al. Comparison of measured utility scores and imputed scores from the SF-36 in patients with rheumatoid arthritis. Medical Care 2005; 43: 79–87. 46. riza-Ariza R, Hernandez-Cruz B, Carmona L et al. Assessing utility values in rheumatoid arthritis: a comparison between time trade-off and the EuroQol. Arthritis and Rheumatism 2006; 55: 751–756. 47. Doan QV, Chiou CF & Dubois RW. Review of eight pharmacoeconomic studies of the value of biologic DMARDs (adalimumab, etanercept, and infliximab) in the management of rheumatoid arthritis. Journal of Managed Care Pharmacy 2006; 12: 555–569. 48. Conner-Spady B & Suarez-Almazor ME. Variation in the estimation of quality-adjusted life-years by different preference-based instruments. Medical Care 2003; 41: 791–801. 49. Kirwan JR, Hewlett SE, Heiberg T et al. Incorporating the patient perspective into outcome assessment in rheumatoid arthritis–progress at OMERACT 7. The Journal of Rheumatology 2005; 32: 2250–2256. 50. Kirwan JR, Ahlmen M, de WM et al. Progress since OMERACT 6 on including patient perspective in rheumatoid arthritis outcome assessment. The Journal of Rheumatology 2005; 32: 2246–2249. 51. Boers M, Brooks P, Strand CV & Tugwell P. The OMERACT filter for Outcome Measures in Rheumatology. The Journal of Rheumatology 1998; 25: 198–199. 52. Heiberg T & Kvien TK. Preferences for improved health examined in 1,024 patients with rheumatoid arthritis: pain has highest priority. Arthritis and Rheumatism 2002; 47: 391–397. 53. Verhoeven AC, Boers M & van der LS. Validity of the MACTAR questionnaire as a functional index in a rheumatoid arthritis clinical trial. The McMaster Toronto Arthritis. The Journal of Rheumatology 2000; 27: 2801–2809. 54. Wolfe F, Michaud K & Pincus T. A composite disease activity scale for clinical practice, observational studies, and clinical trials: the patient activity scale (PAS/PAS-II). The Journal of Rheumatology 2005; 32: 2410–2415. 55. Athale N, Sturley A, Skoczen S et al. A web-compatible instrument for measuring self-reported disease activity in arthritis. The Journal of Rheumatology 2004; 31: 223–228.
840 S. Lillegraven and T. K. Kvien 56. Mosley-Williams A & Williams CA. Validation of a computer version of the American College of Rheumatology patient assessment questionnaire for the autonomous self-entry of self-report data in an urban rheumatology clinic. Arthritis and Rheumatism 2004; 50: 332–333. 57. Kvien TK, Mowinckel P, Heiberg T et al. Performance of health status measures with a pen based personal digital assistant. Annals of the Rheumatic Diseases 2005; 64: 1480–1484. 58. Heiberg T, Kvien TK, Dale O et al. Daily health status registration (patient diary) in patients with rheumatoid arthritis: a comparison between personal digital assistant and paper-pencil format. Arthritis and Rheumatism 2007; 57: 454–460. 59. Greenwood MC, Doyle DV & Ensor M. Does the Stanford Health Assessment Questionnaire have potential as a monitoring tool for subjects with rheumatoid arthritis? Annals of the Rheumatic Diseases 2001; 60: 344–348. 60. Kvien TK. Epidemiology of disability in rheumatoid arthritis. Rheumatology (Oxford) 2002; 41: 121–123.
2 Measuring disability and quality of life in established rheumatoid arthritis Siri Lillegraven
MD
Research Fellow Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
Tore K. Kvien *
MD, PhD
Professor Department of Rheumatology, Diakonhjemmet Hospital and Faculty of Medicine, University of Oslo, Norway
Rheumatoid arthritis is a chronic inflammatory disease with a major impact on physical and psychological health. It can cause severe disability and reduce health-related quality of life, aspects that are important to patients. Thus, it is important to measure disability and healthrelated quality of life in clinical practice and in clinical trials. This article presents an overview of the most important measures of outcome concerning disability and health-related quality of life, including different forms of the Health Assessment Questionnaire (HAQ, MHAQ, MDHAQ, HAQ II), visual analogue scales for fatigue and function, SF-36, Arthritis Impact Measurement Scales (AIMS/AIMS2), the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire, Nottingham Health Profile, Sickness Impact Profile and the utility instruments 15D, EQ-5D, SF-6D and Health Utilities Index (HUI) 2 and 3. Key words: disability; health-related quality of life; rheumatoid arthritis; utility.
INTRODUCTION Rheumatoid arthritis (RA) is a common autoimmune disease that has articular and extra-articular manifestations.1 It has a prevalence of approximately 0.5–1% and is most prevalent in women, with a 2.5/1 ratio between women and men.1 RA can have a major impact on health-related quality of life (HRQoL).2 The aim of this chapter
* Corresponding author. Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, N-0319 Oslo, Norway. Tel.: þ47 22 45 17 50; Fax: þ47 22 45 17 78. E-mail address: [email protected] (T.K. Kvien). 1521-6942/$ - see front matter ª 2007 Elsevier Ltd. All rights reserved.
828 S. Lillegraven and T. K. Kvien
is to present an overview of different instruments that are used to assess disability and HRQoL in patients with RA. What is disability? Several definitions of the word disability have been presented. In a recent review, Leonardi et al3 propose the following: Disability is a difficulty in functioning at the body, person or societal levels, in one or more life domains, as experienced by an individual with a health condition in interaction with contextual factors. Whereas impairment represents disturbances at the organ level caused by a pathological process; disability reflects the consequences of impairment in terms of functional performance. What is health-related quality of life? HRQoL is a broad concept that can be defined as the impact of health on an individual’s ability to function and on the perceived well-being in physical, mental and social domains of life.4 An important part of HRQoL is that it includes a patient’s satisfaction or response to his or her health status and limitations.5,6 The same disease state or limitation can thus affect HRQoL differently across patients, depending on personal factors. The difference between generic and disease-specific instruments Generic instruments are developed for use in patients regardless of disease. One of the major advantages of such instruments is the opportunity to compare results between disease groups, and so to cover a broad variety of disease-related factors. The disadvantages are that generic instruments might lack aspects that can be important in some diseases but not others; they can also be less sensitive to change.6 The disease-specific instruments described in the following sections have been developed for use in patients with RA or other arthritic diseases. Their advantage is that they aim to cover all the important factors in these conditions - exemplified by dexterity in RA – that is, components that might be less important in tools assessing a wider spectrum of diseases. The disadvantage of any disease-specific measure is that the results obtained cannot be compared with results from patient groups with other diagnoses. INSTRUMENTS MEASURING DISABILITY Generic measures SF-36 physical functioning The well-known generic health profile the Short Form 36 Health Questionnaire (SF-36) contains a domain concerning physical functioning. This is based on 10 items regarding limitations in physical activities because of health problems.7 This scale can be used as a measure of physical disability. However, none of the items directly addresses dexterity, which is important in RA.
Measuring disability and quality of life in established RA 829
Other Other generic health profiles (the Sickness Impact Profile, the Nottingham Health Profile) also have items that capture physical limitations and can be used as measures of disability. Disease-specific measures The Stanford health assessment questionnaire The Stanford Health Assessment Questionnaire (HAQ)8,9 was introduced in the 1980s and is now widely used in evaluation of patients with RA. It was initially developed for use in rheumatology, but has also been applied to other diseases. Some investigators will therefore argue that HAQ can be considered a generic instrument. The original, but less used, full HAQ version contains questions concerning five dimensions – disability, economic costs, pain/discomfort, adverse effects of medication, and death – i.e. the original 5Ds for patient outcomes: disability, dollars, discomfort, doctor (iatrogenic consequences), and death. The disability index of the instrument includes questions about the ability of patients to perform 20 activities of daily living, and is most commonly referred to as the HAQ questionnaire, and sometimes as the HAQ disability index (HAQ-DI). Four response categories are available for each question: without any difficulty (score 0), with some difficulty (score 1), with much difficulty (score 2) or unable to do (score 3). The 20 activities are classified into eight categories with two or three activities each. A score is then assigned to each of the eight categories based on the highest score of the items within the category. Patients are also asked about use of aids and devices, and if they need help from another person for activities in any of the eight categories. If category score is lower than 2, it is increased to 2 within any category in which the patient uses a device or help from another person, so that the underlying disability is more accurately represented. It is important to note that HAQ scores without this adjustment will be lower than the scores obtained with the original scoring system. The total HAQ score, with range 0–3, is the mean of the scores for the eight categories.9 MHAQ, MDHAQ and HAQII The Modified Health Assessment Questionnaire (MHAQ)10,11, a modification of the HAQ, keeps one question from each of the eight categories in the HAQ and reduces the number of items to eight. No adjustment of scores is possible. The total MHAQ score is the mean of the scores for each activity. MHAQ can easily be administered in clinical practice but will provide lower scores than HAQ, especially for patients with high disease activity.10 A multidimensional health assessment questionnaire (MDHAQ) has been developed by Pincus et al12 and includes more items, such as demanding physical activities, pain, fatigue, anxiety and depression. The aim of the instrument is to be able to measure disability in patients with healthier conditions and avoid the ceiling effect of HAQ and MHAQ in patients with limited disability. Further, the MDHAQ was developed as a comprehensive measure of disability in a short and user-friendly format and also included questions on other dimensions of health, including stress, anxiety and depression. The same group has developed another revised HAQ – the HAQ II – that only includes 10 items.13 It has been reported to be at least as reliable and valid as HAQ and easier to administer because of the reduced number of questions.13,14
830 S. Lillegraven and T. K. Kvien
To summarize, it is important to remember that several HAQ instruments exist, and that these yield scores that cannot be compared directly. VAS-function A visual analogue scale (VAS) for function has been proposed by Wolfe et al.15 The aim is that this patient-weighted functional assessment scale complements multi-item scales. The VAS-function (VAS-F) yields more high values and fewer low values than the HAQ and HAQ-II.15 It is well correlated to other VAS scales, such as VAS-fatigue and VAS-pain. Further studies are needed to examine if this instrument have potential in clinical practice and research. Performance-based measures Grip strength, walking time, and button test Grip strength, walking time, and button test (rheumatology function tests; RFTs) were formerly used in clinical trials.16 These measures of physical function have been shown to predict later function and mortality, and identify work status.16 Grip strength has also been shown to be associated with radiological damage.17 In more recent years, RFTs have mostly been replaced by questionnaires, but some advocate that they now are underused.16 INSTRUMENTS MEASURING HEALTH-RELATED QUALITY OF LIFE Two main groups of instruments measure HRQoL: profiles and utility instruments. A profile contains separate scores for several dimensions. A utility score provides only one sum score for each patient on a scale from 0.0 (a health state similar to death) and 1.0 (perfect HRQoL). Some of the instruments also allow values below 0.0, representing health states that are considered worse than death. Generic measures: profiles SF-36 The SF-36 is the most widely used generic health status measure.7 It is used in health surveys in the general population as well as in various disease populations. The 36 items in the questionnaire are grouped into eight multi-item subscales measuring physical functioning (10 items), role limitations due to physical health (4 items), bodily pain (2 items), general health (5 items), vitality/energy/fatigue (4 items), social functioning (2 items), role limitations due to emotional problems (3 items) and mental health (5 items), plus one item on reported health transition. Each scale is expressed with values from 0 to 100 and a low score indicates poor health. A utility score, the SF-6D, can be computed from SF-36.18 The SF-36 scores correlate to a variety of disease-specific measures in RA.19 One particular advantage of SF-36 is that it also includes a scale on energy/vitality, a dimension that is considered important by patients but which is not included in the core set of outcomes for clinical trials. The SF-36 is a generic measure, meaning that its concepts are not specific to any age, disease or treatment group. This allows for comparisons of the relative burdens of different diseases and benefits of different treatments. It is suitable for
Measuring disability and quality of life in established RA 831
self-administration and performs similarly to disease-specific measures in RA.20 Table 1 shows SF-36 data from the Oslo RA register,21 as well as data for other of the instruments presented here. Nottingham health profile The Nottingham Health Profile (NHP) is a generic profile and has also been used in RA to some extent.22,23 This instrument contains 38 statements in six dimensions: physical mobility, pain, sleep, emotional reaction, social isolation and energy. The respondent is requested to answer ‘yes’ or ‘no’ to each statement. The scores for the dimension range from 0 (no problems or absence of limitations) to 100 (all potential problems are present). The disadvantage of NHP is that it requests the responder to answer ‘yes’ or ‘no’ to negative statements about health. The advantage of NHP is that it includes sleep and energy as dimensions – both considered important by patients. Sickness impact profile The Sickness Impact Profile (SIP) is a generic profile developed in the 1970s24, and has been less used in rheumatology than the other profiles presented. It comprises 189 items in 14 categories, covering a wide range of behavioral aspects related to sickness. Table 2 includes an overview of the different profiles, including SIP. Generic measures: utility instruments EQ-5D The EQ-5D25,26 captures five health dimensions (mobility, self-care, usual activity, pain/ discomfort and anxiety/depression), with three response categories within each of these dimensions; no problems, some or moderate problems and extreme problems.26 The EQ-5D encompasses 243 different health states and is one of the most widely used utility instruments in medicine.27 One reason for the widespread use may be that EQ-5D is easy to use with only five questions. SF-6D The SF-6D is a relatively new utility instrument in which some of the answers from SF-36 and SF-12 can be recalculated into a utility score.18 It contains six dimensions (physical functioning, role limitations, social functioning, pain, mental health, vitality), each with four to six levels. The opportunity to recalculate answers from SF-36, which is already measured in many clinical trails, makes it possible to reduce the amount of questionnaires in studies. 15D The Finnish 15D captures information from 15 dimensions (mobility, vision, hearing, breathing, sleep, eating, speech, bladder/bowel function, usual activities, mental function, discomfort/pain, depression, distress, vitality and sexual activity)28, with five response categories within each dimension; altogether, 515 health states can be described. It has a simple additive structure, where each of the dimensions has been validated into a certain value.
All patients (n ¼ 1041)
Women (n ¼ 813)
Men (n ¼ 228)
Age < 40 (n ¼ 97)
Age 40-59 years (n ¼ 341)
Age 60-74 years (n ¼ 373)
Age 75 years (n ¼ 230)
HAQ versions MHAQ HAQ
1.58 (0.54) 1.06 (0.75)
1.60 (0.55) 1.13 (0.74)
1.48 (0.50) 0.79 (0.71)
1.31 (0.40) 0.59 (0.57)
1.52 (0.50) 0.90 (0.67)
1.57 (0.51) 1.08 (0.70)
1.79 (0.64) 1.46 (0.81)
AIMS2 dimensions Mobility Walking and bending Hand/finger function Arm function Self-care Household tasks Social activity Support Pain Work Tension Mood
1.88 4.22 2.95 1.65 0.77 1.51 5.37 2.65 4.76 2.22 3.61 2.63
(2.25) (2.76) (2.52) (2.07) (1.71) (2.08) (1.45) (2.22) (2.53) (2.44) (1.95) (1.80)
2.05 4.30 3.20 1.77 0.81 1.63 5.35 2.73 4.86 2.27 3.68 2.67
(2.30) (2.73) (2.52) (2.12) (1.77) (2.13) (1.47) (2.24) (2.51) (2.49) (1.98) (1.83)
1.30 3.93 2.08 1.19 0.63 1.09 5.44 2.35 4.39 2.06 3.37 2.47
(1.99) (2.84) (2.32) (1.79) (1.47) (1.85) (1.35) (2.16) (2.60) (2.30) (1.83) (1.72)
0.88 2.54 1.71 0.69 0.33 0.65 4.91 2.46 3.79 2.08 3.31 2.10
(1.50) (2.32) (1.81) (1.34) (0.94) (1.20) (1.29) (2.04) (2.32) (2.50) (1.70) (1.50)
1.40 3.60 2.81 1.38 0.53 1.22 5.31 2.70 4.61 2.07 3.73 2.43
(1.84) (2.56) (2.40) (1.80) (1.35) (1.75) (1.44) (2.00) (2.60) (2.36) (1.97) (1.77)
1.79 4.41 2.99 1.67 0.68 1.39 5.31 2.78 4.75 2.22 3.56 2.61
(2.09) (2.57) (2.45) (2.08) (1.66) (1.89) (1.41) (2.32) (2.47) (2.44) (2.01) (1.76)
3.25 5.59 3.65 2.44 1.49 2.55 5.75 2.41 5.41 4.06 3.67 3.21
(2.74) (2.87) (2.81) (2.40) (2.25) (2.69) (1.50) (2.46) (2.47) (2.38) (1.91) (1.91)
SF-36 dimensions Physical functioning Role limitations physical Pain General health Vitality Social functioning Role limitations mental Mental health
52.5 32.4 43.9 47.5 42.0 69.4 56.9 70.2
(26.7) (37.9) (20.5) (22.5) (21.2) (27.2) (41.7) (19.7)
50.3 30.5 42.6 46.9 40.6 68.1 56.1 69.5
(26.6) (36.8) (20.1) (22.4) (21.0) (27.5) (41.7) (19.7)
60.1 39.5 48.5 49.5 47.2 74.1 59.5 72.9
(25.7) (40.9) (21.4) (22.8) (21.3) (25.7) (41.7) (19.3)
73.0 52.6 52.2 55.1 47.8 77.8 79.0 75.0
(22.8) (40.3) (20.9) (23.3) (20.9) (25.2) (35.1) (16.2)
58.8 41.3 45.6 49.5 42.4 72.1 65.5 71.7
(25.1) (39.9) (20.0) (23.2) (21.5) (26.4) (41.2) (19.5)
50.5 28.1 43.6 46.3 42.8 70.4 55.6 70.5
(24.3) (35.2) (19.6) (21.9) (20.6) (25.6) (40.6) (19.9)
37.1 16.9 38.5 43.2 37.6 60.0 35.4 65.4
(25.7) (29.8) (21.2) (21.0) (21.1) (29.4) (37.7) (20.0)
832 S. Lillegraven and T. K. Kvien
Table 1. Mean (SD) values for HAQ, MHAQ, AIMS2, SF-36, VAS-fatigue, EQ-VAS, 15D, SF-6D and EQ-5D.
VAS scales Fatigue EQ-VAS
46.6 (29.6) 62.0 (20.9)
48.9 (29.5) 61.6 (20.5)
38.2 (28.3) 63.3 (22.1)
39.5 (31.1) 70.0 (20.4)
46.1 (30.4) 64.7 (20.4)
45.9 (28.6) 61.8 (20.0)
51.7 (28.4) 54.5 (21.2)
Utility scores 15D SF-6D EQ-5D
0.81 (0.11) 0.64 (0.13) 0.60 (0.28)
0.81 (0.11) 0.63 (0.13) 0.60 (0.27)
0.82 (0.11) 0.67 (0.14) 0.63 (0.28)
0.88 (0.09) 0.71 (0.13) 0.68 (0.25)
0.83 (0.11) 0.66 (0.13) 0.62 (0.28)
0.81 (0.10) 0.64 (0.12) 0.61 (0.26)
0.76 (0.11) 0.59 (0.13) 0.55 (0.30)
Data from the Oslo RA register (ORAR). Approximately 85% of RA patients in the area of Oslo are included in ORAR,21 and 1041 (58.1%) of these patients responded to a questionnaire in 2004. AIMS, Arthritis Impact Measurement Scales; HAQ, Health Assessment Questionnaires; SF-36, Short Form 36 dimensions; VAS, visual analogue scale.
Measuring disability and quality of life in established RA 833
834 S. Lillegraven and T. K. Kvien
Table 2. Dimensions of the different generic and disease-specific health profiles. Some similar dimensions have been placed under one heading. Dimensions
Pain Physical Hand / finger /arm function Mobility Household tasks Self-care Activities of daily living Social Social interaction/function Support Work Mental health Emotions Mood Level of tension
Generic profiles NHP
SF-36
SIP
AIMS
AIMS2
RAQoL
Role Physical, emotional Sexuality Other Energy/fatigue Physical contact Sleep Eating Communication General health Recreation and pastimes
Disease-specific profiles
AIMS, Arthritis Impact Measurement Scales; NHP, Nottingham Health Profile; RAQoL, Rheumatoid Arthritis Quality of Life questionnaire; SF-36, Short Form 36 dimensions; SIP, Sickness Impact Profile.
Health utilities index mark 2 and 3 The Health Utilities Index Mark 2 and Mark 3 (HUI2 and HUI3) include a profile and a utility instrument, together describing nearly 1 million health states.29 HUI3 should be the primary choice, whereas HUI2 includes self-care and fertility items. The HUI system, consisting of both HUI2 and HUI3, has been shown to be valid and have a minimal clinically important difference of about 0.03.29 Table 3 shows the properties of the utility instruments presented here. Other generic instruments VAS-fatigue Fatigue is frequently reported as a major factor for reduced quality of life30 by patients with RA. On the VAS-fatigue, the patient is asked to place his or her level of fatigue on
Measuring disability and quality of life in established RA 835
Table 3. Properties of the utility instruments 15D, EQ-5D, SF-6D, HUI2 and HUI3. Utility instrument 15D EQ-5D SF-6D HUI2 HUI3
Potential range
Dimensions
Response categories for each dimension
0.00e1.00 0.59e1.00 0.29e1.00 0.03e1.00 0.36e1.00
15 5 6 7 8
5 3 4e6 3e5 5e6
a scale. The mark is converted into a score between 0 and 100, 0 being absence of fatigue and 100 being major problems with fatigue. Comparative studies have revealed that the VAS-fatigue performs as well or better than more extensive fatigue instruments.31 Thus, VAS-fatigue might be a suitable instrument for use in clinical practice and trials, but it has not yet come into widely use. EQ-VAS EQ-VAS26 is a VAS that asks patients to place their own health on a scale from 0 (worst possible health) to 100 (best possible health). The EuroQol group25 developed this scale, and sometimes the combination of EQ-5D and EQ-VAS is called the EuroQol instrument. The EQ-VAS is not a true utility instrument. In the validation of utility instruments, patients are asked to sacrifice something (money, life years). When patients are asked to mark their HRQoL on a VAS scale, no such sacrifice is necessary. Thus, the score will on an average be lower. Disease-specific profiles The arthritis impact measurement scales The Arthritis Impact Measurement Scales (AIMS) was developed in 1980 to measure the health status of patients with arthritis32,33with seven demographic items and 55 health status items. It was later revised into the AIMS2, which is now mostly used. The arthritis impact measurement scales 2 The AIMS234 is an expanded and revised version of AIMS. It is a multidimensional disease-specific instrument with 78 items capturing information in 12 areas of health (mobility level, walking and bending, hand and finger function, arm function, self-care tasks, household tasks, social activity, support from family and friends, pain, work, level of tension, mood). These 12 scales can be aggregated into five major dimensions (physical functioning, social interaction, pain, work and affect). The score is from 0 to 10 (10 being worst possible health). AIMS2 also includes a separate question that addresses the patients’ priorities for improvement in health. The patients are asked to check three of 12 areas where they would most like to see improvement. A short form of AIMS2 (SF-AIMS2) has been validated in both French35 and Norwegian36 patient populations and seems to perform well.
836 S. Lillegraven and T. K. Kvien
The rheumatoid arthritis quality of life questionnaire The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is an RA-specific quality of life measure that comprises 30 statements about unfulfilled needs related to activities relevant to patients.37,38 Each question is answered with ‘yes’ or ‘no’. Possible scores range from 0 to 30, the higher score representing worse quality of life. RAQoL is quick for the patients to complete, valid and has been examined in the Dutch37,39, British37 and the Swedish populations.40
Practice points Questionnaires assessing health have been shown to be useful and important in clinical trials. HAQ has been shown to be the most important predictor of mortality, followed by other patient self-reported variables.41 These instruments were better predictors than radiographics, laboratory findings, and clinical examination. The choice of instrument should be based on the situation and the goals of the use. Is the setting a clinical trial or is the goal to evaluate the effect of interventions outside a trial? Instruments that have been validated should be chosen to optimize the results. Within a study setting, it is usually recommended to use instruments that have been used in similar studies, to facilitate comparisons between studies. Performance-based measures are currently less used than before but have been shown to be reproducible and reliable measures and predictors of later function and premature death in patients with RA, and can be especially suitable for clinical trials of longer duration (> 5 years).16
Research agenda Several utility instruments have been examined and used in RA42–47,with differing results. At the present time, there is no consensus regarding choice of utility instrument. Clearly, the choice of instrument will affect both the results of future studies of new biologic agents and their cost-effectiveness.48 Studies and recommendations are needed to decide which instrument is best suited for drug trials. Patients should be more strongly involved in the identification of important patient-reported outcomes reflecting disability and health-related quality of life.49,50 In particular, outcome measures of dimensions not included in current profiles should be validated and tested according to accepted criteria and procedures.51 Examples of such dimensions are sleep, fatigue, and well-being.49,50
Measuring disability and quality of life in established RA 837
Currently used measures focus on patient perceptions of quality of life. However, patient priorities/perceptions of importance and relevance are usually not included. Some studies have indicated that a focus on patient priorities might give additional information.52,53 The issue of patient priorities for improvement in combination with measures of perception require further attention on the research agenda. Core measures of disease activity include measures of pain, disability and patient global (ACR core set), whereas the composite disease activity measures DAS-28, CDAI and SDAI include only patient global assessment of disease activity. Wolfe et al have proposed a composite disease activity score, the Patient Activity Scale (PAS) based on pain, disability and patient global score.54 Further studies should be performed to establish a composite score based on patient-reported measures of dimensions of relevance to them, i.e. dimension identified on the basis of the perceived impact of RA. Patients can complete questionnaires in any setting that is independent from the health care setting. Thus, patient-reported measures can be completed frequently at home. Electronic tools for capturing information have a major potential for the future, via the internet55, computers in the hospital56 or personal digital assistants (PDA).57,58 Current research indicates that electronic versions of questionnaires addressing health-related quality of life in patients with RA perform similarly to a regular pencil/pen version. Measurements of health-related quality of life perform well regarding validity and responsiveness on a group level. However, studies addressing repeated measures of patient reports have shown great day-to-day variability.58,59 These findings indicate that a change in patient-reported measures also has to exceed the measurement errors to be a true improvement or deterioration. Such levels for HAQ have, for example, been shown to be around 0.4 on a scale from 0.0 to 3.0.59,60
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