The purpose of this study was to develop, refine and perform the initial validation of a subject self-assessed LDIQ questionnaire in a large English-speaking population of SLE patients. We found good overall agreement between the newly-developed LDIQ questionnaire and the SDI. In the community-based NDB stage 3 of this study, in which participants completed the questionnaire by mail, rather than in the rheumatologist’s office, the mean agreement was slightly lower at 82%, suggesting that physicians and patients may have had some influence on each others’ responses. The specificities of individual LDIQ items were generally greater than 80% compared to the SDI results. Sensitivities were variable and were lower for low prevalence damage items, such as myocardial infarction, mesenteric insufficiency, and gastrointestinal stricture or surgery, and pancreatic insufficiency (all of which had <1% prevalence). The low prevalence of certain types of damage does limit the interpretation of comparisons of the two instruments. Correlations between the SDI and the LDIQ instruments were high for most organ damage domains in both the office-based and mailed validation studies. This suggests that the LDIQ questionnaire may be useful and reliable alternative to the SDI in assessing SLE-related damage in population studies.
In developing this index, we expected a moderate degree of disagreement between physicians and patients regarding specific damage questions. For physicians, over-reporting should not occur, but under-reporting might occur. For example, specialty lupus physicians might be unaware of diagnoses made by other physicians, might have out of date records, or might not adequately examine the eyes for cataracts or retinal damage. Such under-reporting might be major problem when general physicians, not lupus specialists, provide data. More important, however, is misreporting by patients. Although subject under-reporting would be expected for some items, as subjects may not have had or understood all of the data that physicians had, over-reporting was the more common misclassification. Questions concerning end-stage renal disease, cognitive impairment, alopecia, skin scarring, claudication, retinal changes, muscle atrophy and osteomyelitis, which were confusing to subjects or which showed high disagreement with clinicians’ responses in the pilot study were subsequently refined and did show improved performance in the validation study. Overall, we found the patient damage score to exceed the physician score by 1.9 units and the correlation between patients and physician damage score to be 0.65.
The subjects in the first two stages of this study were consecutive, willing English-speaking patients in major SLE centers. They were relatively young (mean age in early 40s), with mean disease duration of over ten years, and SDI scores ranging from 0 to 9, and a wide variety of SLE manifestations (Tables and ). Non-random subject refusal could have introduced a selection bias or limited the generalizability of the results. Stage 3 involved community-based patients, which improves the generalizability of the study. While we targeted an 8th grade reading level, given SLE’s complicated manifestations, many of the challenging words exceeded this level (e.g.pulmonary hypertension, claudication, cardiomyopathy, and pericarditis). We placed these terms in quotes, aiming for patients’ recognition. When stratified by participants’ educational level, correlations with rheumatologists’ SDI scores were actually higher among subjects with fewer years of formal education.
One limitation of this validation study is that the LDIQ was assessed using responses of subjects’ physicians on the SDI as the gold standard. The assumption was that the physicians’ responses were correct, but this may not have always been true. As our analyses suggested, this is particularly likely for subjects who have had SLE for many years and suffered some of their SLE-related damage early in their disease (possibly before they were known to their current physician). The SDI was validated and endorsed by the American College of Rheumatology (ACR) in 19966
and has since been validated in a number of international centers representing different health care systems6, 10, 13
. These studies have demonstrated that this instrument can reliably identify changes in damage seen in both active and inactive disease and that, at one point in time, there is no correlation between the SDI score and disease activity, measured by the SLEDAI (a disease-activity scale), or health-related quality of life, measured by the Medical Outcome Survey (MOS) Short-Form 20 (SF-20)6, 10, 32, 33
. The SDI therefore functions as intended, measuring accumulated damage in patients with SLE, independent of simultaneous disease activity and or health-related quality of life (although these three facets of disease are inextricably linked as with progression over time15-17
). Higher scores on the SDI are predictive of poor outcomes, defined as death or hospitalization34-36
. African-Caribbean, African-American, Hispanic and Asian patients accumulate more damage as assessed by the SDI than do Caucasian patients12, 37
, suggesting a racial/ethnic influence on the expression of this disease. SDI assessed damage clearly increases with disease duration 38
. The SDI therefore provides an important outcome measure in SLE, both for studies of prognosis and in the assessment of the long-term effects of the disease process and its medical therapy. Whether the self-assessed LDIQ will be predictive of long-term clinical outcomes and mortality in the same way as the SDI will be the subject of future investigation. Age, disease duration and race/ethnicity have known influences upon the severity of SLE-related damage and are also likely to influence the subjects’ understanding of their disease and the questionnaire.
If the purpose of the LDIQ is to evaluate an individual patient, the level of concordance that we found would be unacceptable. However, if the purpose is to evaluate groups of patients in outcomes research, particularly in community settings, the degree of concordance may be acceptable if the damage scale is substantially predictive of health status and outcomes. Data from the 3rd
stage of this study, the observational cohort, suggests this is the case. In this community-based cohort study, the LDIQ was more useful for identifying health status and outcomes than standard assessment measures. In this setting, the higher LDIQ value of 4.9, compared with 3.4, likely reflects increased age, SLE duration39
, and other characteristics of the NDB cohort. It is possible that patients followed in academic lupus centers and are more educated about SLE (regardless of educational level) than are community patients, and therefore more likely to answer the questions correctly, as suggested by the lower agreement between physician and patient scores was lower in this cohort. Regression analyses on age and SLE duration (not shown) indicated that about 0.8 units of the 4.9 LDIQ score in the current study can be accounted for by age and SLE duration. Both variables have been shown to associated with increased damage as measured by the SDI 39, 40
. Correlations between SLE disease activity (by SLAQ) and LDIQ were as good as those between SLAQ and patient comorbidity index, and patient global assessment. As shown in , the LDIQ is a “better” comorbidity index than the standard comorbidity index with respect to outcomes that can be considered fixed or relatively fixed. Similarly, LDIQ is less correlated to patient activity variables like fatigue and HAQ than is the patient global. This is not surprising, as the LDIQ measures the domain of damage, which is conceptually different than the disease activity domain. The data of suggest the LDIQ is performing as expected in these cross-sectional analyses. In one study of 54 SLE patients the SDI was correlated with the SF-36 PCS, MCS and patient global at values of 0.34, 0.02, and 0.14 41
. In the current report the LDIQ correlation with these variables was 0.432, 0.141, and 0.166, suggesting similar, or perhaps stronger, associations between LDIQ and self-reported patient variables compared with the SDI data.
We have also found that stepwise increases in the LDIQ were associated with clinically important increases in direct medical costs, work disability, comorbidity, and hospitalization (). We also noted in that different domains contributed different amounts to the final LDIQ score. We noted that the two domains that contributed most to the LDIQ also were the domains most strongly associated with disability status and health status (). The associations were weaker with the other domains, reflecting the uncommonness of some of the outcomes, and that many of the outcomes are also common in individuals without SLE, and the weighting design of the SDI authors. However, attempts to reweight the SDI after the use of Rasch analysis have shown the current weighting system to be clinically appropriate42
The LDIQ has been translated into several languages. In one validation study, a total of 887 SLE patients and 40 rheumatologists with a special interest in SLE participated: 659 of the patients completed the Spanish (611 in Latin America, 30 in the US, and 18 in Spain), 140 the Portuguese (122 in Brazil and 18 in Portugal) and 88 the French (all in Canada) versions of the LDIQ as well as the SDI43
. In that study, the SDI total score was 1.9 and the LDIQ total score was 3.7 and the correlation between LDIQ and SDI was 0.61.
Quantifying irreversible organ damage from SLE is important for characterization of SLE populations and for outcomes research. The results of this study are encouraging and suggest that the LDIQ, a self-reported questionnaire completed by patients rather than physicians, may be able to reliably assess SLE-related damage in patients, providing an alternative to the physician-completed SDI for lupus patients who are primarily managed in the community rather than in specialist lupus centers. Physicians caring for SLE patients in the community may be unfamiliar with the use of this assessment tool, nor have the time or motivation to complete it. This currently limits the use of the SDI to large academic specialist centers, thus the generalizability of research findings to these settings. While it may not be possible to use these two instruments interchangeably within the same study, the LDIQ could be employed for future studies where the collection of physician-assessed data is impossible, ultimately allowing the expansion of investigations of the impact of SLE beyond academic medical centers. The LDIQ has preliminary validity, but comparative longitudinal studies will be required to determine its reliability, sensitivity to change over time and real value in assessing organ damage from SLE in cohort studies.