Physical function measurement

The most important category of outcome in arthritis might well be disability (Boers et al., 1994; Fries et al., 1980; Fries, 1983). In RA, disability is a common outcome and has a major impact on daily life, as well as socioeconomic

138 consequences (Boers et al., 1994; Fries et al., 1980). The level of disability has a significant impact on patients and society in terms of the financial and social costs of the disease (Boers et al., 1994; Fries et al., 1980; Fries, 1983). There are different instruments for assessing disability in RA, but the most widely used are self-reported questionnaires (Lillegraven & Kvien, 2007). One of the most widely used disease-specific arthritis tools is the HAQ-DI which was used (ARAMIS, 2009; Bruce & Fries, 2005; Felson et al., 1993; Fries et al., 1980). The two most frequently used questionnaires in arthritis are HAQ (ARAMIS, 2009; Fries et al., 1982) and AIMS (Meenan et al., 1980).

Many other instruments were developed to be used in RA, but only HAQ and AIMS offer the possibility to assess their potential value and have a sufficiently validated widespread focus (Fitzpatrick, 1996). Other older scales, on the other hand, tend to be fairly limited and insensitive to functional disability (Bowling, 2003). Since disability in RA is multidimensional, other versions have been developed, such as the modified–HAQ (Pincus et al., 1983) and the multidimensional HAQ with more items (Anderson et al., 2010; Pincus et al., 1999), but these are less commonly used in clinical trials and in daily practice.

Fries et al. (1980) developed the HAQ in 1978. The HAQ was among the first instruments to have been based on generic, patient-centred dimensions for measurement of physical function (Fries et al., 1980), and use of this questionnaire is now indicated in most RA clinical trials (ARAMIS, 2009; Bruce

& Fries, 2005; Fries et al., 1980) and it is regarded as the gold standard outcome

139 measure for assessing functional status (Bruce & Fries, 2005). Sensitive to change of functioning status, even over short time intervals, HAQ is authorised and recommended by the ACR. It is available in more than 60 languages and is supported by a bibliography of more than 500 references (ARAMIS, 2009; Bruce

& Fries, 2005).

The HAQ is originally designed as a disease‐specific questionnaire. However, it has been developed and successfully applied for assessing functional disability in a variety of rheumatic diseases (Bruce & Fries, 2005; Ramey et al., 1992). HAQ can be administered in diverse disciplines and, with properly designed adaptations, in different cultures without any impact on its reliability or validity (ARAMIS, 2009; Bruce & Fries, 2005).

There are two versions of HAQ: full HAQ and short HAQ (2-pages HAQ) (Bruce

& Fries, 2005). The full HAQ assesses the dimensions of postponing death, avoiding disability, drug side effects, discomfort and pain, and economic costs, while the short HAQ is comprised of the HAQ disability index (HAQ-DI) and the HAQ patient global health status and pain VAS (Bruce & Fries, 2005). The difference between full HAQ and short HAQ is that the items in the short HAQ remain constant, while in the full HAQ, items like drug side effects and costs as well as supplemental sections on demographics, lifestyle and costs are periodically tailored to uncover specific hypotheses or research questions to capture the long-term impact of chronic illness (Bruce & Fries, 2005).

HAQ-DI (Appendix 5)

140 The HAQ-disability index (HAQ-DI) is used in this study as the primary outcome measure and consists of eight weighted categories that are designed to measure a person's ability to dress, arise from a chair or bed, eat, walk, perform basic toileting (hygiene), reach, grip, and perform normal activities. Sexual activity was included in an earlier version (Bowling, 2004) but was removed after a reluctance to report this (Fries et al., 1980). Each category is scored on a 4-point scale (Bruce

& Fries, 2005; Bruce & Fries, 2003).

 0 = Is able to perform the activity without any assistance.

 1 = Is performing the activity with some difficulty.

 2 = Is performing the activity with great difficulty (needs assistance of others to perform the specific activity).

 3 = Unable to do the task (cannot perform the specific activity).

Interpretation of the test result may be classified as follows (Bruce & Fries, 2003):

 0. 00 to 1. 00 mild to moderate difficulty or disability.

 1. 01 to 2. 00 moderate to severe difficulty or disability.

 2. 01 to 3. 00 severe to very severe difficulty and disability; dependence on others.

Thus, a high HAQ indicates loss of functional capacity – so the lower the HAQ score, the better the functional status (Bruce & Fries, 2003).

Advantages of HAQ-DI

141 We chose the HAQ-DI as the primary outcome measure because functional limitation is an important factor in RA patients, which can be easily measured by the HAQ-DI. Functional disability is one of the main outcomes in a core set of eight endpoints for RA (Boers et al., 1994). Disability is a common outcome in RA and has an impact on daily life as well as socio-economic consequences. More than one third of working people are no longer able to work five years after the onset of the disease, indicating the consequence of the disease on working status (Scott et al., 2003; Scott et al., 2000).

HAQ-DI rather than AIMS was chosen for this study for the following reasons:

 The HAQ-DI is regarded as a self-administered questionnaire completed in five minutes and scored in less than one minute.

 It can be administered face-to-face (ARAMIS, 2009; Bruce & Fries, 2005) or in a telephone interview and it has been validated for both.

 The questionnaire can also be emailed to patients (ARAMIS, 2009; Bruce

& Fries, 2005).

 HAQ-DI is a good measure of function and it was used extensively among clinicians in USA, UK and Europe (Bruce & Fries, 2005; Ramey et al., 1992).

 HAQ-DI is regarded as concise, reliable, valid, sensitive to change and can be either self-administered or interviewer-administered. It is also suitable for use in the community (ARAMIS, 2009; Bruce & Fries, 2003).

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 AIMS covers physical, social and emotional wellbeing. However, it was not used in this study because the emotional wellbeing was evaluated in a separate questionnaire (HADS).

 HAQ-DI is designed to evaluate a patient's level of functional ability by including questions about activities involving both upper and lower extremities, also with fine movements (Bruce & Fries, 2003).

Moreover, the main reasons to investigate predictors for HAQ-DI are as follows:

1. To recognise the factors that predicts a poor outcome as early as possible in order to treat patients showing such characteristics more aggressively (Jansen et al., 2000). This approach may help to prevent joint damage and preserve functional capacity.

2. To test whether the various disease parameters correlate with the functional status.

3. This study first used the univariate analysis to explore which factors are independently predicting functional disability in patients with RA.

Reliability and validity of the HAQ-DI

The HAQ-DI is sensitive to change and is a good predictor of prospective disability and costs (ARAMIS, 2009; Michaud et al., 2003; Wolfe & Zwillich, 1998). It has had verified reliability and validity in different languages and contexts (ARAMIS, 2009). Literally hundreds of studies have demonstrated its validity (ARAMIS, 2009; Bruce & Fries, 2005). There is an agreement that the HAQ-DI has face and content validity (ARAMIS, 2009; Bruce & Fries, 2005;

143 Ramey et al., 1992). Correlations between the questionnaire or interview scores and task performance ranged from r = 0.71 to 0.95 demonstrating criterion validity among RA patients (ARAMIS, 2009; Bruce & Fries, 2005).

HAQ-DI scoring

A large and growing body of HAQ-DI literature has confirmed and emphasised that when there are scores for less than six of the eight categories, the score cannot be validly calculated (ARAMIS, 2009; Bruce & Fries, 2005). The Standard way of scoring takes into account the use of aids/devices. Three steps are needed for calculating HAQ-DI overall score (with aids/devices):

1. Each category contains at least two specific subcategory questions; the highest subcategory score determines the value for each category, unless aids or devices are used.

2. Adjust the score if there is any use of aids/devices and/or help from another person.

3. To obtain a HAQ-DI score of 0-3, the sum of category scores is divided by the number of categories answered (zero = best-, three = worst-functioning). There must be responses in at least 6 of the 8 categories or else a HAQ-DI cannot be computed.

HAQ VAS (pain score) (Appendix 5)

The measurement of pain is an essential dimension in patients with RA. HAQ VAS

a double-anchored VAS was designed to obtain data relative to the presence or absence of arthritis-related pain and its severity (Bruce & Fries, 2003; Bruce &

144 Fries, 2005). This scale measures pain on a horizontal VAS with “no pain” at one end (scored 0) and “severe pain” at the other (scored 100) (ARAMIS, 2009; Bruce

& Fries, 2003; Bruce & Fries, 2005; Fries et al., 1982). The goal is to obtain information from patients on how their pain has tended to be over the past week, although it is understood that pain may be reported to have diverged over the course of a day or from day to day (ARAMIS, 2009; Bruce & Fries, 2003; Bruce

& Fries, 2005).

The VAS line is standardised to 15 centimetres in length. To indicate the severity of their pain, patients are instructed to place a vertical mark on the line (ARAMIS, 2009; Bruce & Fries, 2005).

If a patient reports a percentage, multiply the percentage by three. Use the midpoint if a patient puts more than one mark. If a patient points a horizontal line below the pain scale, and not a vertical one, the midpoint of that line is taken. If the line starts at the beginning of the scale, measure to the end of the line, not the middle.

Calculating the pain score: \Measure the distance in centimetres and multiply by 0.2; this provides a score from 0 to 3. For example, if the mark is at 5cm, 5 x 0.2 yields a pain score of 1.0.

145 Pain was used as a secondary outcome measure for the following reasons:

 Pain is one of the most prominent symptoms in the majority of people with RA (McKenna & Wright, 1985; Walsh & McWilliams, 2012).

 Pain is a common purpose for primary care consultation (Uhlig et al., 2002).

 Pain is a major cause for increased health care costs (Crook et al., 1984).

 Previous studies have included pain as an outcome to measure the effects of hydrotherapy for patients with RA (Rintala et al., 1996).

 Pain is one of the core set of eight endpoints for RA (Boers et al., 1994).

 Pain is easy to score without being a burden to the patient (Huskisson, 1974).

 VAS is regarded as a reliable and valid measure of pain, primarily when comparing individuals over time for three to four times (Huskisson, 1974).

HAQ-GWB (Wellbeing score) (Appendix 5)

The scale that measures GWB is on a horizontal scale with “very well” at one end (scored 0) and “very poor” at the other (scored 100). GWB was used as a secondary outcome measure for the following reasons:

 RA imposes an immense burden on the individual's ability to cope, and may greatly diminish QoL and psychological wellbeing (Fitzpatrick et al., 1988).

 It incorporates a VAS, which is easy to score and is without burden to the patient (Huskisson, 1974).

146 5.2.4.2 Health-related quality of life (HRQoL) measurement

QoL is the awareness of a person’s position in life in the context of the culture and value systems in which they live, and in relation to their goals, expectations, standards and concerns (WHOQOL group, 1995). Across a wide spectrum of diseases and conditions, there has been an upsurge of interest in the development of a generic instrument that can be used to measure HRQoL (Hawthorne, et al., 2000; Hurst et al., 1997; Hurst et al., 1994; Rabin et al., 2011a). These generic questionnaires have advantageous outcomes and, besides just the beneficial and detrimental effect of medication on the individual, capture the overall impact of disease (Cheung et al., 2009; Hawthorne, et al., 2000; Hurst et al., 1997; Rabin et al., 2011a).

Health status profiles characteristically measure an individual’s health status across different dimensions, to reflect their HRQoL. In Study One, generic measures of HRQoL were measured by using EQ-5D (Brooks, 1996; Cheung et al., 2009; Hurst et al., 1997; Rabin et al., 2011a). There are other well-validated, popular, generic health-related QoL scales (also called health-status scales) that have been used to assess outcomes in rheumatology such as the SF-36 (Ware, 1993; Ware & Sherbourne, 1992), the Nottingham Health Profile (NHP) (Hunt et al., 1985), the Sickness Impact Profile (SIP) (Bergner et al., 1976), the Quality of Wellbeing Scale (QWB) (Balaban et al., 1986), the Functional Status Questionnaire (FSQ) (Jette et al., 1986) and the Framer Quality of Life Scale (Rudick et al., 1992).

147 De Jong et al. (1997) developed a specific questionnaire called RA quality of life (RAQoL). This instrument is used to measure pain and fatigue in addition to other disease specific issues (De Jong et al., 1997). This instrument has been found to have excellent test-retest reliability, good internal consistency and good content validity; however, the main difference between the RAQoL and others is that it uses a qualitative approach and lengthy interviews (De Jong et al., 1997). It has been recommended that QoL should be assessed using questionnaires rather than interviews (Berndtsen et al., 1994; Guyatt et al., 1993).

EQ-5D

EQ-5D is a validated generic QoL instrument developed by the EuroQol Group (Hawthorne, et al., 2000; Rabin et al., 2011a). EQ-5D is a generic, simple measure of health for clinical and economic appraisal of healthcare. It consists of two parts: a descriptive profile (EQ-5D tariff) for measuring economic health (Appendix 6) and a VAS (EQ-5D VAS) (Appendix 7) for measuring health status (Drummond et al., 2005; EuroQol Group, 1990). EQ-5D essentially consists of two parts: the EQ-5D descriptive system called EQ-5D 3L or called EQ-5D tariff.

The EQ-5D visual analogue scale (EQ-5D VAS) (Hawthorne, et al., 2000; Rabin et al., 2011a). Costs per quality-adjusted life year (QALY) were derived from health states measured for economic health (Drummond et al., 1997; Drummond et al., 2005; EuroQol Group, 1990). EQ-5D is a self-administered questionnaire easily completed by respondents without the need for support or help within a few minutes (Hurst et al., 1997; Rabin et al., 2011a).

148 EQ-5D tariff (Appendix 6)

The subjects report their level of ability on that day depending on five items; each item includes three ordinal response levels; this is called EQ-5D-3L. The five categories are namely mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each category has three levels: no problems, some problems, severe problems. This decision results in a single-digit number expressing the level selected for that dimension. The digits for five dimensions can be combined in a five-digit number describing the respondent’s health state. It should be noted that the numerals 1-3 have no arithmetic properties and should not be used as a cardinal score. These categories are coded to form a health profile, for example 11111 indicates no problems for any dimension, which therefore equals perfect health, while state 11223 indicates no problems with mobility or self-care, some problems with performing usual activities, moderate pain or discomfort and extreme anxiety or depression, and 33333 indicates extreme problems in every dimension, resulting in the worst imaginable health state possible (EuroQol Group, 1990; Rabin et al., 2011a). The health profiles classified them to one of 245 unique EQ-5D tariffs (or ‘health states’) ranging from one, indicating the best imaginable health state, and zero, representing death. Some health states attract negative values (to -0.594) indicating that from a societal perspective, these health states are regarded as worse than death (Hurst et al., 1997; Rabin et al., 2011a).

Instructions to respondents are included in the questionnaire (EuroQol Group, 1990; Wolfe & Hawley, 1997). The EQ-5D has been used with patients with RA (Hurst et al., 1997), and there is evidence that it has moderate construct validity

149 (Spearman rho = .71) and reliability (ICC = .70) when used with patients (n = 82) with knee OA (Fransen & Edmonds, 1999).

EQ-5D VAS (Appendix 7)

Records of the response has self-rated health on a vertical, VAS, where the endpoints are labelled ‘best imaginable health state’ and ‘worst imaginable health state’.

In Study One, the EQ-5D was used because it is widely accepted as an easy-to-use tool for measuring the relative cost-effectiveness of an intervention, while measuring health status at the same time (Hurst et al., 1997; Rabin et al., 2011a).

The original intent in this study was to assess the CE of the two interventions in terms of cost per QALY gained.

HRQoL or QoL was used interchangeably within this thesis. It was used in secondary outcome measures for the following reasons:

 In RA patients, the assessment of HRQoL is relevant and is important in both clinical research and daily clinical practice (Hawthorne, et al., 2000; Kvien & Uhlig, 2005).

 Changes in HRQoL provide important information in RCTs &

observational studies (Hawthorne, et al., 2000; Kvien & Uhlig, 2005).

 Priorities for resource allocation within the NHS were based increasingly on evidence of the CE of medical interventions on

150 HRQoL, providing further consideration (Hawthorne, et al., 2000;

Hurst et al., 1997).

EQ-5D was chosen for this study rather than other outcome measures such as SF-36, NHP, and SIP because:

 The EQ-5D has been used with RA patients (Hurst et al., 1997).

 There is evidence that it has moderate construct validity (Spearman rho = 0.71) and reliability (intraclass correlation coefficient (ICC) = 0.70) when used with OA patients (n = 82) (Fransen and Edmonds, 1999).

 EQ-5D is quick, simple to use and easy to complete (Hawthorne, et al., 2000; Rabin et al., 2011a).

 It offers less complex health-state descriptors over the others and is more easily comprehended by patients (Hawthorne, et al., 2000; Hurst et al., 1997; Rabin et al., 2011a).

 SF-36, NHP and SIP are lengthy and time consuming. SF-36 functional ability scale concentrates mainly on mobility; therefore, it is unlikely to be sufficiently sensitive as an outcome measure in rheumatology (Hurst et al., 1997).

 The reliability of the EQ-5D index and EQ-5D VAS is better than all other instruments except the HAQ, and is sufficiently reliable for group comparisons (Hurst et al., 1997).

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 It is responsive to change and therefore valid as an outcome measure in clinical trials, audit and health economic studies (Drummond et al., 2005;

Hawthorne, et al., 2000).

An updated version of the EQ-5D, called the ‘EQ-5D-5L’, was published in 2011 (Rabin et al., 2011b). It includes the five dimensions, but each dimension has five response levels rather than three (Rabin et al., 2011b). EQ-5D-5L was designed in order to potentially reduce ceiling effects, maintain feasibility and significantly improve reliability and sensitivity (discriminatory power) (Rabin et al., 2011b). It has been validated for arthritis but its reliability and responsiveness has not yet been demonstrated (Rabin et al., 2011b).