A comparison of the MOS-HIV and SF-12v2 for measuring health-related quality of life of men and women living with HIV/AIDS

Background The purpose of this study was to examine the relationship between the Medical Outcomes Study-HIV Health Survey (MOS-HIV) and the SF-12v2 to determine if the latter is adequate to assess the health-related quality of life (HRQoL) of men and women living with HIV/AIDS. 112 men and women living with HIV/AIDS who access care at a tertiary HIV clinic in Hamilton, Ontario were included in this cross-sectional analysis. Correlation coefficients of the MOS-HIV physical and mental health summary scores (PHS and MHS) and the SF-12v2 physical and mental component summary scales (PCS and MCS) were calculated along with common sub-domains of the measures including physical functioning (PF), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF) and mental health (MH) to explore the relationship between these two HRQoL measures. The sub-domains role physical (RP) and role emotional (RE) of the SF-12v2 were compared separately to the sub-domain role functioning (RF) of the MOS-HIV. Weighted kappa scores were calculated to determine agreement beyond chance between the MOS-HIV and SF-12v2 in assigning a HRQoL state (i.e. low, moderate, good, very good). Results The MOS-HIV had mean PHS and MHS summary scores of 47.3 (SD = 11.5) and 49.2 (SD = 10.7) respectively. The mean SF-12v2 PCS and MCS scores were 47.7 (SD = 11.0) and 44.0 (SD = 10.4). The MOS-HIV and SF-12v2 physical and mental health summary scores were positively correlated (r = 0.84, p < 0.001 and r = 0.76, p < 0.001). All common sub-domains were significantly correlated at p values from < 0.001 to 0.034. Substantial agreement was observed in assigning a HRQoL state (Physical: κ = 0.788, SE = 0.095; Mental: κ = 0.707, SE = 0.095). Conclusions This analysis validates the SF-12v2 for measuring HRQoL in adult men and women living with HIV/AIDS.


Background
Health-related quality of life (HRQoL) measures a person's health status taking into account multiple dimensions including physical or functional, psychological and social well-being and often relies on patient self-report. Patrick and Erickson broadly define HRQoL as the "value assigned to the duration of life as modified by the impairments, functional states, perceptions, and social opportunities that are influenced by disease, injury, treatment, or policy [1]." A paradigm shift has occurred with HIV now being considered a chronic illness due to the advancement and availability of treatment and care. Introduction of highly active anti-retroviral therapy (HAART) has resulted in a significant decrease in HIV-related morbidity and mortality across the globe; however, people living with HIV/AIDS (PHAs) continue to face a variety of health-related challenges, which can affect many aspects of their quality of life. As a result, there has been increasing interest in understanding HRQoL in the context of HIV infection across a broad spectrum of HIV research including clinical trials, observational studies and community-based research. It is important, however, to ensure that the tools used to measure HRQoL are in tune with the current state of the HIV epidemic and reflect the experience of PHAs in their local and geographical context, while minimizing the burden placed on those who participate in research studies.
Over 17 generic and HIV-specific HRQoL measures are used in HIV research today and there is no consensus on which measures are best, especially considering that many of these measures were developed in the pre-HAART era [2]. In a comparative review by Clayson et al., the SF-36 was identified as the generic measure with the greatest evidence supporting its use in HIV/ AIDS research [2]. The Medical Outcomes Study HIV Health Survey (MOS-HIV) was identified as one of the preferred HIV-specific measures since it is brief and practical to administer, the input of PHAs was used in its development, there is well-established evidence for its reliability, validity and responsiveness and it has been successfully used in clinical trials [2]. Shahriar et al. countered Clayson's review stating that there was insufficient evidence to recommend the use of the MOS-HIV over the SF-36 and that more head-to-head comparisons were needed [3].
The MOS-HIV is a 35-item questionnaire that includes eleven dimensions of HRQoL including general health perceptions (GHP), bodily pain (BP), physical functioning (PF), role functioning (RF), social functioning (SF), mental health (MH), energy/vitality (EV), cognitive functioning (CF), health distress (HD), overall quality of life (QL) and health transition (HT) allowing for the generation of physical (PHS) and mental (MHS) health summary scores. Development of the MOS-HIV began in 1987 and items selected from the SF-20 were the foundation for its construction [3][4][5]. The MOS-HIV was developed to provide a brief, comprehensive measure of functional status and well-being of PHAs enrolled in large-scale clinical trials and has been shown to be internally consistent and responsive to a number of outcomes including infections, adverse events, increased symptoms and AIDS-related events [2,4,5]. The MOS-HIV has also been used in studies with a variety of patient groups including treatmentnaïve, asymptomatic PHAs to those with more advanced HIV and opportunistic infections. MOS-HIV items are rescaled to a number between 0 and 100, with a higher score reflecting better health and HRQoL [4][5][6].
The 12-item short-form (SF-12v2) health survey, now in its second version, was developed out of a strategy to construct a shorter version of the SF-36 Health Survey reflecting the same sub-domains including general health perceptions (GHP), bodily pain (BP), physical functioning (PF), role physical (RP), role emotional (RE), social functioning (SF), mental health (MH) and energy/ vitality (EV) [4,7]. The SF-12v2 reproduces more than 90% of the variance of the physical and mental component summary scales of the SF-36 in the general US population, takes significantly less time to complete than the SF-36, reducing burden on research participants; and demonstrated high two-week test-retest reliability correlations for both the physical (r = 0.89) and mental (r = 0.76) health summary scores [6,8] . Han  et al. demonstrated the SF-12v2 to be a reasonable and  effective replacement for the SF-39, a similar measure to  the MOS-HIV, in studies of people living with advanced  HIV disease by comparing five domains of the SF-12  (namely physical functioning, general health perceptions, bodily pain, mental health and energy/fatigue) to the SF-39 [9]. This analysis demonstrated that the burden of data requirements for both participants and investigators as well as redundancy of questions asked could be reduced by using the SF-12v2 [8].
The purpose of this study was to give further rationale for using the SF-12v2 in HIV research by examining the relationship between the MOS-HIV and the SF-12v2 to determine if, when compared to the HIV-specific MOS-HIV, the SF-12v2 is an adequate measure to assess the health-related quality of adult men and women living with HIV/AIDS.

Methods
The study population consisted of 112 adult men and women living with HIV/AIDS who accessed care at the McMaster University Medical Centre Special Immunology Services outpatient clinic in Hamilton, Ontario and were enrolled in the Canadian HIV Vascular Study, a multi-centre, prospective cohort study examining the relationship between HIV infection, anti-retroviral therapy and cardiovascular disease. The Canadian HIV Vascular Study was approved by the Hamilton Health Sciences/McMaster University Faculty of Health Sciences Research Ethics Board; all participants gave their informed consent prior to their inclusion in this study and analysis of their data. MOS-HIV and SF-12v2 questionnaires completed on the same day during the Canadian HIV Vascular Study baseline interview were used. The MOS-HIV served as the reference standard as it is the primary HIV-specific HRQoL measure used in clinical and observational HIV research; there is no evidence that the SF-39, a similar HRQoL scale, has ever been used in HIV research. The continuous PHS and MHS of the MOS-HIV and the PCS and MCS of the SF-12v2 were assessed for normality. Correlations between baseline physical and mental health summary scores of both measures were calculated using SPSS v17; Pearson correlation coefficients were calculated because of the lack of skew in the distributions of the summary scores. Pearson correlation coefficients were used to investigate the relationship between common subdomains of the MOS-HIV and SF-12v2 including physical functioning (PF), bodily pain (BP), general health perceptions (GH), energy/vitality (VT), social functioning (SF) and mental health (MH). The sub-domains role physical (RP) and role emotional (RE) of the SF-12v2 were compared separately to the domain role functioning (RF) of the MOS-HIV as these two domains capture the overall "role functioning" measured in the MOS-HIV. Pearson correlation coefficients and the Multitrait-Multimethod Matrix method as outlined by Campbell and Fiske [10] were used to assess convergent and discriminant validity. Convergent validity indicates the degree to which subdomains of the measures are related whereas discriminant validity indicates to what extent the sub-domains are not related theoretically; both convergent and discriminant validity were assessed statistically [11]. A cut-off of r ≥ 0.70 was chosen to determine the degree of convergent validity [12,13]; a cut-off of r < 0.85 was chosen to assess discriminant validity [11].
We also investigated agreement between the two measures in assigning individuals to a HRQoL state, for example, low, moderate, good and very good HRQoL.  [14] were calculated using software by Cyr and Francis [15] in order to determine the chance-corrected agreement between the MOS-HIV and SF-12v2 in assigning individuals to levels of HRQoL.
A secondary analysis was conducted using the baseline clinical and HRQoL data from 96 of the men and women in the cohort from whom we had complete baseline data in order to determine the clinical validity of the SF-12v2 compared to the MOS-HIV. Pearson correlation coefficients were calculated in univariable analysis for all clinical variables of interest with each HRQoL summary score from both measures. Four linear regression models were created in SPSSv17 utilizing the physical health and mental health summary scores of both the SF-12v2 and MOS-HIV as outcome measures. The overall fit of each model was assessed and standardized beta coefficients for each clinical variable of interest were reviewed for statistical significance and contribution to the model. The following clinical variables were included in each regression model: age, gender, years living with HIV, smoking (current and former), current marijuana use, drug use (including cocaine and heroin), current receipt of a NNRTI-based or PI-based HAART regimen, nadir CD4 cell count and average number of hours slept each night. These variables were chosen because they have shown to affect physical or mental HRQoL in the literature [17][18][19][20][21][22][23][24][25][26][27][28]. Table 1 presents baseline characteristics of the 112 men and women living with HIV/AIDS who were included in the analysis. The cohort was predominantly male with a mean age of 49.1 years (SD = 8.2) and Caucasian ethnicity. The HIV transmission risk factor cited most frequently was sex with other men (61.6%) followed by heterosexual/bisexual sex (29.5%) and injection drug use (6.3%). The cohort had a mean CD4 T-lymphocyte count of 507 cells/ml of blood at their baseline study visit (SD = 280.3) and had lived with HIV, on average, for 12.0 years (SD = 7.6). Table 2     Lastly, the univariable and multivariable analyses investigating clinical correlates of HRQoL between the SF-12v2 and MOS-HIV demonstrated moderate agreement (Table 6). There was similar directionality and magnitude of association between the two measures for both the physical and mental health summary scores. In univariable analysis, a history of drug use was associated with a lower physical health summary score for both the MOS-HIV [r = -0.216 (95% CI -0.399, -0.017)] and SF-12v2, however the correlation was not significant for the SF-

Discussion
This preliminary analysis suggests that the SF-12v2 is an appropriate measure of health-related quality of life of men and women living with HIV/AIDS compared to the MOS-HIV demonstrating high correlation and good convergent and discriminant validity when compared to the physical and mental health summary scores of the MOS-HIV and common sub-domains. Furthermore, the   SF-12v2 had substantial agreement with the MOS-HIV in assigning individuals to a specific HRQoL status and determining clinically relevant correlates of HRQoL. It is important to point out that this analysis does not account for the HRQoL domains of cognitive functioning, health distress and health transition, which are captured in the MOS-HIV but are not represented in the SF-12v2. These domains are used to derive the mental health summary score of the MOS-HIV, which may help to explain the weaker correlation between the measures in the MHS as well as the differences in determining clinically relevant correlates of HRQoL. If the SF-12v2 is used as a HRQoL measure in any HIV research study, it would have to be with the caveat that these three HRQoL domains were not important outcomes or were not relevant to the population under study.
It should be noted that the mean physical and mental health summary scores were lower than the mean score of 50 for the reference population. This supports the literature that despite the advancement of HAART and decline in HIV-related morbidity and mortality, people living with HIV continue to experience health-related challenges and generally have lower physical and mental HRQoL scores when compared to the general population. A cross-sectional questionnaire-based study conducted by Miners et al. found that men and women living with HIV in the United Kingdom scored lower on all five domains on the EQ-5D quality of life measure including mobility, self-care, usual activities, pain/discomfort and anxiety/depression irrespective of similarities in age and gender [22]. Univariable and subsequent multivariable regression analysis demonstrated that people living with HIV had significantly lower utility and visual analogue scale scores on the EQ-5D compared with the general population; HIV infection independently decreased the utility and visual analogue scale scores of the EQ-5D by 20% [22]. In addition, the mean mental health summary scores were relatively higher for people completing the MOS-HIV compared to the SF-12v2. This may reflect the additional domains captured in the MOS-HIV (i.e. health distress, health transition, etc.) that are combined to determine the mental health summary score or may have arisen due to chance.
The SF-12v2 is currently being used in HIV research in Canada to better understand the HRQoL of individuals living with HIV/AIDS including assessing changes over time, but had not been formally compared to the MOS-HIV. The Canadian HIV Vascular Study investigators chose the SF-12v2 over the MOS-HIV in order to reduce questionnaire burden on participants, and the SF-12v2 is also being used in the Ontario HIV Treatment Network Cohort Study to understand yearly changes in HRQoL. The SF-12v2 is a contemporary HRQoL measurement tool with accessible language and efficiency in its administration. Ease in reading and comprehending the SF-12v2 would also result in fewer errors by the participant.
Although this is not necessarily synonymous with the level of understanding of the intended meaning of the items, anecdotally, the authors have experienced minimal issues in interpreting the SF-12v2, but have often had questions from participants completing the MOS-HIV, including redefinition of colloquial language such as "pep," "blue" and "down in the dumps." The MOS-HIV typically takes much longer to complete than the SF-12v2. Locally, participants involved in research at the McMaster University Medical Centre usually need 5 to 10 minutes to complete the MOS-HIV, whereas   PHAs via focus groups or in-depth interviews prior to inclusion of the MOS-HIV and SF-12v2 in this analysis; this would have offered another interesting perspective to this comparison. This analysis may not be generalizable to all PHAs. The cohort was comprised predominantly of men with an average age of 48.6 years (ranging from 31 to 75 years) whose major HIV transmission risk factor was intercourse with other men; the study sample is reflective of the early HIV epidemic and may not be comparable to today's population of people living with HIV/ AIDS. Eighty-nine per cent were of Caucasian ethnicity and only 12.6% of the cohort were women, therefore, caution should be taken when attempting to apply these results to people from different ethnocultural communities and gender identities. These findings must also be considered with caution due to the relatively small sample size.

Conclusions
This preliminary analysis suggests that the SF-12v2 is an efficient and practical HRQoL questionnaire taking, on average, less than two minutes to complete. This HRQoL measure may enable timely collection of quality of life data in broader areas of research than in the past while reducing the redundancy and questionnaire burden placed on participants. Confirmatory studies in larger and more representative populations are needed.