ME/CFS is a disabling condition with a high impact on individuals and society, which causes a substantial economic burden [28
]. We measured the functional status and well being of a well characterised sample of individuals with ME/CFS and their careers, using SF-36, a widely used and well-validated instrument, which provides generic (i.e. universally-valued, and not specific to age, disease or condition or treatment) measures of disease impact on physical, physiological, social functioning and roles [11
] Generic instruments best capture the 'total burden of disease' by expressing the impact of the disease on functioning and well being. Therefore, unlike disease-specific measures, they can be adequately used for comparisons between people with ME/CFS and healthy individuals and those with a range of other diseases [29
]. While SF-36 version 2 represents an improvement on its predecessor, it is still meaningful to compare results which use different versions of this instrument [11
The use of norm-based scores allowed comparisons between scales and component summaries, and helped identify which aspects of quality of life are most affected. The physical and mental health summary measures provide convenient ways to quantify physical and mental health status. Individual-based scores below 40 and group mean scores below 47 may indicate impairment of function. For example, low scores in the physical component scale may relate to limitations in self-care and reduced well-being. Low scores in the mental component scale may relate to frequent psychological distress, and emotionally-driven social and role disability [11
The scores for the Physical and Mental Health Component summaries and the scales within each of these domains were considerably and consistently lower in people with ME/CFS, when contrasted with individuals with a range of other chronic diseases. By using normalized scores, we were able to show that the scores within the physical domain were even lower than those in the mental domain, although all scales showed very low values. This demonstrates that ME/CFS is not only physically disabling, but also has a significant impact on mental health.
Physical Health Component summaries at the levels found in our study (mean score 26.8) have been shown to relate to an inability to climb one flight of stairs in over 90% of those with similar scores, with three-quarters of those with this scoring level having difficulties at work, with over half needing to reduce the amount of time spent at work, and two thirds rating their health as 'fair' or 'poor' [11
]. This score corresponds to around the 5th
percentile of the US general population, and is lower than the 25th percentiles of 10 other chronic diseases we used for comparison purposes. The lowest observed mean score was for 'Role-Physical', indicating limitations in functionality for these patients. The values found for this scale are comparable to the 25th percentiles of those with limited use of arm(s) and leg(s), and are lower than the 25th
percentiles of those with 9 other conditions.
The mean Mental Health Component summary of 34.1 is comparable to the mean score of those with depression (MID lower than 3), and to the 25th percentile of those with lung disease. It is lower than the 25th percentile of all the other comparison conditions, and corresponds to around the 9th percentile of the general population. The highest values in this domain were for the 'Mental Health' scale, but these were still very low, equivalent to around the 10th percentile of the general population.
The 'Role-Physical' scale was one the most affected of all, suggesting this could be a suitable outcome measure in ME/CFS. The vitality scale has been widely used in ME/CFS research, as it is directly related to the perception of low energy levels typical of those with chronic fatigue. This scale has often presented strikingly low results in people with ME/CFS, on a '0 to 100' score, and this might have helped to reinforce its suitability as an outcome measure in this disorder. In our study, this was 15.5, representing the lowest of all scores. Although still low when normalized scores were used, the 'Vitality' score ranked as the 4th highest score among the 8 health domains scales (the highest score was for Mental Health). This indicates that lack of energy in itself may well not be the most disabling feature of ME/CFS. It also illustrates the inappropriateness of the '0 to 100' score for comparing scales. 'Vitality' scores have inherently low values, as illustrated by the finding for the US general population, where the mean for this score is 58.3. In comparison, the mean score for 'Role-Pyia' in the same population is 82.5, with scores for the remaining scales varying between 75.0 ('Mental Health') and 87.4 ('Role-Emotional').
We have shown that the quality of life of those caring for people with ME/CFS is also affected. In most cases, their scores were lower than those of healthy individuals of the same age group. Interestingly, the Mental Health Component summary and scales within this domain were more sharply reduced, compared with the summary and scales within the Physical Component. In addition, the significant correlations demonstrated between the Mental Health Summary and 'Role-Emotional' scores of patients and their carers suggest that those patients who are less able to carry out emotional roles and whose mental health is more affected represent a greater burden to their carers. These findings may demonstrate the intensity of the emotional pressures on those caring for people with ME/CFS.
Previous studies have shown that a considerable impact on the functional status and well-being or the quality of life of people with ME/CFS [12
]. These studies varied in relation to the methods used, including the reference population, how cases were ascertained, and how quality of life has been measured. When SF-36 was used, the scales scores were not normalized, which made comparisons difficult. However, we have also presented our results using the standard scoring system (0-100 scores), to enable comparisons with these previous studies. While low scores were consistently found previously [19
], they were not as low as in our study. Possible explanations, other than differences in populations and methods, include the specificity of the case definitions we used, which might have excluded cases that would have been positive if other, more complacent diagnostic criteria were used. The fact that the scores of cases meeting the Canadian criteria were consistently lower than those not meeting the criteria further suggests that diagnosis specificity is related to disease severity, and that diagnostic criteria such as the Canadian may be more appropriate for research studies investigating risk factors and disease biomarkers.
Study strengths and limitations
Our study strengths include the large sampling frame, selection of participants from wide geographic areas, well characterised patients, standardised recruitment procedures and the use of a well validated instrument to measure functional status and well being. The response rate for carers was not particularly high, but all scores were similar in patients whose carers completed the SF-36 and those who did not (data not shown), giving some indication that participation was unlikely to have selected a particular sub-group of carers. Our comparisons were made with references based on the US population. Although comparisons would ideally have been made with the population in the same UK regions, large US studies provide reliable and readily available population norms, including for the general population, specific diseases, gender, and age groups. In addition, the SF-36 instrument has been widely available internationally [11
], including in the UK [34
], where general population scores have been similar and in some cases slightly higher than those in the US. The comparisons of scores with those with other chronic diseases and the healthy population were based on different age groups, i.e. 18-64 years in our study and 18 and over in the SF-36 population survey. As we would expect population scores to be increased by the exclusion of elderly individuals, restriction of the comparison to those under 65 only would, if anything, tend to show a more dramatic contrast between those with ME/CFS and other disease population groups. The large differences between ME/CFS patients and those in other groups reassure us that the differences are genuine, and would be expected to remain if we used controls from the same geographical area.
The results of the study highlight the disabling nature of ME/CFS. However, the lack of biomarkers and the fluctuating nature and lack of specificity of symptoms makes disease characterisation and disability assessment challenging. Our study supports the potential value of SF-36 as an instrument to characterise incapacity in people with ME/CFS, and particularly that of specific scales, such as the 'Role-Physical'. They may represent a reliable outcome measure indicating case severity for use in observational and interventional studies. However, as the scales are based on patient report, they should ideally be used in combination with other instruments providing objective outcome measurements of physical [35
] and neuro-cognitive abilities [36
]. A good example of an objective measure of disability is that of cardiopulmonary exercise testing with measurement of VO2
max, anaerobic threshold and maximal heart rate and respiration. This test has shown abnormal results in people with ME/CFS [35
], and could perhaps be used more often in disability assessments, in combination with instruments based on patient report such as the SF-36.