In this study, subjects with MS were interviewed on an individualized measure to evaluate the impact of the disease on their QOL. The results of the interview generated a list of domains that were most important to the QOL of persons with MS. The domains identified were work, fatigue, sports, social life, relationships, walking, cognition, balance, housework and mood. These were then mapped onto generic utility measures to estimate the extent to which they captured domains that were important to persons with MS.
There was no one generic utility measure that captured all of the domains important to persons with MS. For example, fatigue, which affects 75 to 90% of patients with MS
[54–57] was not included in the EQ-5D or the HUI measures. Walking, another commonly reported symptom was not found in the SF-6D. Cognition was not found in the EQ-5D or the SF-6D. Work, sports, and social life were not found in the HUI2 or HUI3. This was not surprising as the HUI measures were developed with the intention of evaluating ‘within-the-skin’ experiences that excluded social interaction
[58–60]. Balance and relationships were not included in any of the utility measures.
The generic utility measures were clearly missing domains that were important to people with MS. Out of the 10 domains that persons with MS identified as being central to their QOL, only 3 of them were included in the HUI2, 4 were included in the HUI3, 4 were included in the EQ-5D and 6 were included in the SF-6D. Furthermore, the generic utility measures included several domains that were not important to persons which were sampled in the study, such as pain, self-care, hearing and manual dexterity.
To tackle the issue of lack of content validity, one emerging area of interest in the literature is the development of disease specific “bolt-ons” or dimension extensions to generic utility measures
. Another emerging area of interest is the development of disease-specific utility measures, which have been developed for stroke
, pulmonary hypertension
, urinary incontinence
 and erectile dysfunction
. Recently, Versteegh et al.
 derived a MS specific utility measure from the Multiple Sclerosis Impact Scale-29 (MSIS-29) using Rasch analysis. The authors selected 8 out of 29 items from the original questionnaire. Some important dimensions such as social life, work and mood were included while others such as walking, sports and physical fatigue were omitted.
There are several potential benefits to using disease specific utility measures in clinical and cost-effectiveness research. First, disease specific utility measures are designed to include domains that are specific to a disease, and therefore, are likely to be more sensitive to smaller change over time than generic measures. Second, not only do these measures provide descriptive information on the various dimensions of health, but also provide a value for each one, thus allowing trade-offs to be made between the domains. Disease-specific utility measures serve the potential to overcome one of the challenges associated with disease specific health profiles - that domains cannot be combined into a single index, which makes it difficult to conclude whether an intervention was effective or not. For example, if a treatment has a positive effect on physical health but a negative one on mental health, unless we know the relative importance attached to each domain, it is impossible to determine whether the intervention resulted in a net improvement or decline in QOL/HRQL. Furthermore, disease-specific utility measures can be used to calculate QALYs and make decisions on the cost-effectiveness of different treatments in MS.
A clinician reported outcome (ClinRO) is an assessment of the status of a patient’s health condition that is made by an observer with professional training (i.e. clinician)
. ClinRO are commonly used for endpoints that cannot be directly measured by the patient (e.g. EDSS to quantify level of disability in MS). An observer-reported outcome (ObsRO) is an assessment that is made by an observer without professional training (i.e. non-clinician observer such as a teacher or caregiver)
. This type of evaluation is typically used when the patient is unable to self-report. A patient reported outcome (PRO) is any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or other observer (e.g. symptoms, QOL, HRQL)
[68, 69]. PROs play a complementary role in outcome assessment by providing evidence on the benefit or harm of a treatment from the patient’s perspective. Utility measures are one type of PRO. In outcome assessment, utility measures not only provide information on the benefits and harms of a treatment, but are also useful for economic applications by producing QALYS. This information can provide policy and decision makers with a means of evaluating the costs and cost-effectiveness of different treatment options for a health condition.
The first step in evaluating the validity of scores produced by a PRO is an assessment of content validity, before any other forms of validity (i.e. construct validity) are undertaken. Content validity of a PRO can be judged only by the individuals or populations being assessed (i.e. the patients themselves). The global aim of this study was to address this very question of whether generic utility measures captured domains that were important or relevant to people with MS. The results of this study suggest that many important domains in MS are not captured by generic utility measures, therefore questioning the content validity of such measures in MS. This in turn, adds doubt to the interpretability or meaningfulness of scores produced by these measures for this population.
It is important to target measures to people to ensure that the impact of a disease and its treatment are adequately and reliably captured in a clinical trial
[70, 71]. If a PRO includes domains that are not impacted upon by the disease or its treatment, it will not be able to capture clinically meaningful change. By targeting to the disease, measures are more likely to be sensitive to small but important clinical changes. Furthermore, the ability of PROs to detect small changes is important in determining the statistical power or the necessary sample size required for a clinical trial
The results of our study revealed that the commonly used 4 generic utility measures (HUI2, HUI3, EQ-5D and SF-6D) do not capture the majority of domains important to MS. Among these generic measures, the SF-6D captured the most number of domains (6 domains) that were important to MS. Our findings suggest that the SF-6D, compared to the other generic utility measures, may be the most appropriate one to use in MS. The PGI index can be used to evaluate the clinical effectiveness of different interventions in MS. However, because the PGI was not developed using multi-attribute utility theory (hence is not a utility measure); it cannot be used for cost-utility analysis.
Ideas for future directions that build directly from this work are the use of MS specific “bolt-on” items or dimensions to generic utility measures
. This study has identified potential items important to MS, such as fatigue that can be used as add-ons to existing generic utility measures. Other areas of potential research that can build directly from this work are the development of an MS specific utility measure that will only include dimensions pertinent to the disease.
A particular feature of this study is that we purposely sampled people with MS diagnosed in the era of Magnetic Resonance Imaging (MRI) technology and availability of disease modifying drugs
. As these are the people who are faced with treatment decisions, a method of valuing changes on the most important domains of QOL affected by MS would be the most relevant for this population.