Abstract
Background:
Social health is an important concern in persons with Huntington’s disease (HD); however, there is little literature examining this construct in this population.
Objective:
While cross-sectional data supports the clinical utility of two Neuro-QoL social health measures in persons with HD, data is still needed to establish their longitudinal validity.
Methods:
Participants (N = 358) completed baseline and at least one follow-up (12- and 24-month) assessment that included the completion of Neuro-QoL Social Health computer adaptive tests (CATs) and short forms (for Ability to Participate in Social Roles and Activities [SRA] and Satisfaction with SRA). Test-retest reliability was examined using intra class correlations, and one-way ANOVAs with Bonferroni post-hoc contrasts were used to determine whether there were group differences among premanifest, early- and late-stage HD participants on the Social health measures. In addition, standardized response means were used to examine longitudinal responsiveness, and mixed or general linear models were used to examine change over time (relative to self-reported change on an associated anchor item about social health and clinician-rated change based on Total Functional Capacity scores from the UHDRS).
Results:
Test-retest reliability of the measures was excellent (ICCs ranged from 0.82 to 0.87 across the different measures) and persons with greater disease burden reported more problems with social health than those at earlier stages in the disease process (all p < 0.0001). Responsiveness was supported for all measures except the Ability to Participate in SRA CAT; participants who had self-reported or clinician-rated declines in health generally had 12- and 24-month declines on the Neuro-QoL measures.
Conclusions:
Findings indicate that these measures may be useful for studies attempting to assess change in social health over time.
Keywords: Huntington’s disease, patient-reported outcomes, health-related quality of life, social health, validity
INTRODUCTION
Huntington’s disease (HD) is inherited as an autosomal dominant, neurodegenerative disorder that causes progressive declines in motor, behavioral, and cognitive function [1–6] which in turn can have a detrimental impact on health-related quality of life (HRQOL; i.e., physical, emotional, cognitive, and social well-being; [7]). Social participation has long been recognized by the World Health Organization (WHO) as a significant domain of HRQOL [8], and this is supported by existing HD literature. Qualitative work indicates that social health concerns are just as important as mental and physical health concerns. Persons with HD discuss social health as frequently or more often than mental or physical health [7]. Additionally, data indicate that individuals with HD exhibit clinically significant problems in social HRQOL, as persons with HD score one standard deviation worse than the general population on the Social Functioning Domain of the SF-36 [9].
Despite evidence that social health is an important HRQOL concern in HD, few studies have examined it in HD [7, 9, 10], and of those, we are unaware of any interventions designed to enhance social health in these individuals. One possible explanation for this gap is due to the lack of research on the psychometric properties of the few existing measures of social health. While the Neuro-QoL Ability to Participate in Social Roles and Activities (SRA) and Satisfaction with SRA measures were developed and validated in a diverse sample of neurological conditions [11], there is only one cross-sectional report that supports the reliability and validity of these measures in persons with HD [12]. Although the Neuro-QoL social health measures were found to have excellent internal consistency reliability, convergent and discriminant validity, and known groups validity [12], there were no data to support longitudinal reliability and responsiveness to change over time, which is crucial when assessing efficacy of clinical interventions. Thus, the current study determined the longitudinal validity and test-retest reliability of the Neuro-QoL social function measures in a sample of premanifest and manifest persons with HD at baseline, 12-, and 24-month assessments. We hypothesized that social function would decline over time while retaining differences between the original disease severity subgroups. Additionally, we expected that individuals with significant health declines, both self-reported and clinician-rated, would exhibit non-negligible effect sizes for decreases in social HRQOL across assessments.
METHODS
Data for the current analyses were collected through the HDQLIFE study, a longitudinal study that examines HRQOL in persons with HD over the course of 24 months [13], Participants were required to have a positive gene test and/or a clinical diagnosis of HD, be ≥18 years, and able to provide informed consent (cognitive status confirmed using a standard assessment when this was in question; [14]) in order to be eligible for this study. Recruitment involved eight HD outpatient clinics across the United States (Los Angeles, CA; Iowa City, IA; Indianapolis, IN; Baltimore, MD; Ann Arbor, MI; Golden Valley, MN; St. Louis, MO; Piscataway, NJ), as well as the use of online medical record data capture systems [15]. In addition, recruitment for this study was carried out in conjunction with the PREDICT-HD study, a global cohort study with the purpose of assessing early symptoms of HD in early manifest and premanifest individuals [16]. Participants involved in Predict-HD were invited to opt-into this study and complete the self-report survey measures if they were participating at a data collection site that was also enrolling for this study. Participants were also referred through the National Research Roster for Huntington Disease, articles/advertisements in HD-specific newsletters and websites, HD support groups and HD specialized nursing home units.
Study visits involved the completion of an in-person assessment, which was followed by a computer based self-report HRQOL survey (through Assessment CenterSM, an online data collection platform [17]; the combined study visit lasted approximately two hours. Twelve- and 24-month study visits were identical to the baseline visit with the exception of the collection of family history data and basic demographic data (which only occurred at the baseline visit). At baseline, participants provided informed consent and participated in a hospital, clinical, or home visit. At 12- and 24-month visits, participants who were unable or unwilling to be seen in-person, but who wanted to continue their participation, were given the option of completing a telephone interview. A subsample of participants (n = 24) completed a retest within 3 days of the initial testing session. All data were obtained in accordance with local institutional review boards and after obtaining informed consent from each participant.
Measures
Demographic variables and medical record data
Participants provided information about age, gender, marital status, race, and ethnicity. Medical record data were used to confirm HD diagnosis and the CAG repeat length of the HD gene mutation (>35 repeats are required for an HD diagnosis).
Health related quality of life assessments
All HRQOL measures were administered as a computer adaptive test (CAT), plus static short form (SF). CAT administration involved a minimum of 4 items and a maximum standard error (SE) of 3.0.
Self-reported assessments.
The Neuro-QoL measurement system evaluates HRQOL in populations with neurological conditions [11, 18]. We administered Neuro-QoL measures of Ability to Participate in SRA, which assesses one’s ability to maintain usual social roles, such as work and familial obligations, and Satisfaction with SRA, which assesses satisfaction while participating in social roles and responsibilities. Resulting scores are on a T-metric (M = 50, SD = 10); higher scores indicate better function. These measures were administered at all three time-points.
At each follow-up visit, participants were asked to complete four “anchor” items, which were used to assess global ratings of change (Supplementary Table 1); two of the anchor items were used to assess the longitudinal validity of the Neuro-QoL Ability to Participate in SRA measures (these anchor items focused on changes in social relationships/activities), and the other two were used to assess the longitudinal validity of the Neuro-QoL Satisfaction with SRA measure (these anchor items focused on satisfaction with social relationships/activities). For each time comparison (baseline to 12-months, 12- to 24-months, and baseline to 24-months), participants were dichotomized into two groups depending on their response to each of the anchor items, resulting in four dichotomies (i.e., 8 groups) per time comparison. Supplementary Table 2 denotes the size of the anchor groups across each of the time comparisons.
Clinician-rated assessments.
The Unified Huntington Disease Rating Scale (UHDRS) [19] is a standardized clinician-rated measure of motor functioning, cognitive ability, day to day functioning, and independence. The Total Motor Scale (TMS) and Total Functional Capacity (TFC) scale were used to classify participants in this study as pre-manifest or manifest (which was further divided into early- and late-stage; [20]) The final question on the TMS ask for the rater to score a diagnostic confidence level (DCL) for the participant, on a scale of 0 (Normal) to 4 (symptoms unequivocal of HD with >99% certainty), to determine whether the participant has motor symptoms consistent with manifest HD. If the participant scored less than a 4, they were rated as having premanifest HD. The TFC scale, which measures independence in a series of tasks (e.g., finances, chores, activities of daily living), was used to determine HD stage for manifest participants. Participants who scored between 7–13 on the TFC were rated as having early-HD and scores from 0–6 indicated late-HD [21, 22].
The TFC was also used to characterize clinician-rated change over time. Baseline TFC scores were subtracted from both 12- and 24-month scores, and 12-month TFC scores were subtracted from 24-month scores to calculate clinician-rated change in functioning across visits. These change scores were then used to classify participants into two groups: those with declines in functioning (i.e., TFC scores that got worse at follow-up) and those with no change or improvements at follow-up [23]. This resulted in participant groups with decline (n = 48) and no change/improvements (n = 209) in clinician ratings from baseline to 12-months, decline (n = 42) or no change/improvements (n = 242) from baseline to 24-months, and decline (n = 40) or no change/improvements (n = 216) in clinician-ratings from 12- to 24-months.
Statistical analysis
Statistical analyses were performed using SAS 9.4 software [24]. Demographic information was examined using frequency tables with chi-square (for categorical data; Fisher’s Exact tests when expected cells counts <5) and one-way Analysis of Variance (ANOVA; for continuous data) to depict differences between the three stage groups (i.e., premanifest, early- and late-stage). For each time point, descriptive data for all measures were calculated and stratified by stage.
Known groups validity and reliability
One-way ANOVAs with Bonferroni post-hoc contrasts were used to determine whether the three groups differed on social measures. Partial eta-squared (np2) effect sizes were calculated to determine the amount of variance accounted for by disease stage; np2 effect sizes of 0.01 were considered small, 0.06 was considered medium, and 0.14 was considered large [25]. Intraclass correlation coefficients (ICC) were calculated to determine 1 to 3-day test-retest reliability. Minimum acceptable criterion for test-retest reliability was set at ≥0.70 [25].
Longitudinal responsiveness
Responsiveness was evaluated using standardized response means (SRM) effect sizes, which were calculated by dividing the average change from baseline to follow-up (12- and 24-month) by the standard deviation of the change [26, 27]. SRMs were calculated for the health decline group and for the no change/improvement in health group with respect to both the self-reported change anchors (i.e., social activities and social relationships) and clinician-rated change in function (TFC). Effect sizes for change in HRQOL social health scales between 0.00 and |0.19| were considered “negligible”, |0.20| to |0.49| were small, |0.50| to |0.79| were medium, and ≥|0.80| were considered large [26]. We hypothesized that participants who reported declines in social health would have small to moderate effect sizes (i.e., ≥−0.20) and that those who reported no change/improvement would have negligible changes (i.e., −0.19 to 0.19).
Change over time
Change over time in HRQOL social health was examined using a series of restricted maximum likelihood (REML) mixed linear models (MLMs) that utilized an unstructured covariance structure. MLMs were conducted for each of the Neuro-QoL Social health measures to observe HRQOL differences across different time frames (baseline to 12-months and 12 to 24-months), and relative to the different anchor types (i.e., self-reported anchors and clinician-rated anchor). Fixed effects for time and social health anchors (those with self-reported/clinician-rated declines, versus those with no change or improvements), and an interaction term between time and anchor was used to examine temporal variations between the two groups; person level differences were represented by random effects. Baseline to 24-month change was examined using a series of general linear models (GLMs). Separate models were conducted for each of the Neuro-QoL Social health measures, again relative to different anchors (e.g., self-reported anchors and clinician-rated anchors). Least-square means and standard errors were calculated for the two change groups for these models. Significant declines in social HRQOL for the health decline group (for both self-reported and clinician-rated anchors) would provide support for responsiveness.
We consider adequate responsiveness assuming ≥75% of results are in agreement with the proposed hypotheses [28].
RESULTS
Study attrition and sample description
At baseline, 152 participants had premanifest HD, 149 were early-stage, and 57 were late-stage HD. Of the 152 premanifest participants, 110 (72.4%) had a DCL of 0–1 while 42 (17.6%) had a DCL of 2–3 (prodromal). A total of 324 individuals (90.5%) completed the 12-month assessment, and 285 (79.6%) completed the 24-month assessment. Of those participants who were missing the 24-month visit (n = 73), 32 were lost to follow-up, 10 were unable to return or ineligible due to worsening symptoms, 11 withdrew consent or were unwilling to return, and 20 were lost due to “other” reasons (e.g., death, multiple reasons for termination, terminated by examiner). When compared to participants who completed all three assessments, the participants who did not complete the 24-month assessment were more likely to have late-stage HD (χ22 = 21.4; p < 0.0001). Additionally, those who dropped out were more likely to have a higher number of CAG repeats (OR = 1.11; p = 0.001). The following analyses included 358 individuals with either premanifest (n = 152) or manifest HD (early-stage HD n = 149; late-stage HD n = 57); Table 1 provides descriptive data for this sample.
Table 1.
Demographics of HD Participants, stratified by baseline disease stage
| Variable | Premanifest HD | Early-HD | Late-HD | Combined Sample |
|---|---|---|---|---|
| (n = 152) | (n = 149) | (n = 57) | (n = 358) | |
| Age (Years)* | ||||
| M (SD) | 43.0 (12.4) | 53.2 (11.8) | 54.8 (10.8) | 49.1 (13.0) |
| Gender (%) | ||||
| Female | 64.5 | 53.7 | 54.4 | 58.4 |
| Male | 35.5 | 46.3 | 45.6 | 41.6 |
| Race (%) | ||||
| White | 98.0 | 95.3 | 93.0 | 96.1 |
| African American | 0.0 | 1.3 | 7.0 | 1.7 |
| Other | 1.3 | 3.4 | 0.0 | 1.9 |
| Not Provided | 0.7 | 0.0 | 0.0 | 0.3 |
| Ethnicity (%) | ||||
| Not Hispanic or Latino | 92.1 | 92.0 | 96.5 | 92.7 |
| Hispanic or Latino | 1.3 | 4.7 | 0.0 | 2.5 |
| Not Provided | 6.6 | 3.3 | 3.5 | 4.8 |
| Education (# of years)* | ||||
| M (SD) | 16.1 (2.8) | 14.8 (2.8) | 13.9 (2.3) | 15.2 (2.8) |
| Marital Status (%) | ||||
| Single, Never Married | 15.1 | 15.5 | 8.9 | 14.3 |
| Married | 69.1 | 58.1 | 64.9 | 63.9 |
| Separated/Divorced | 13.2 | 18.9 | 22.8 | 17.1 |
| Widowed | 0.0 | 3.4 | 3.5 | 2.0 |
| Living with Partner | 2.6 | 4.1 | 0.0 | 2.8 |
| CAG Repeats | ||||
| M (SD) | 41.9 (2.6) | 42.7 (3.8) | 44.1 (6.8) | 42.4 (3.6) |
Indicates significant group differences: the premanifest group was younger than both the Early-HD and Late-HD groups (F[2, 355] = 35.16; p < 0.0001); the premanifest group had more years of education than both the Early-HD and Late-HD groups (F[2, 349] = 16.32; p < 0.0001); the Late-HD group had a higher proportion of African Americans (7.0%) than either of the other two groups (Fisher’s Exact p = 0.01); premanifest participants and Early-HD participants had significantly lower CAG repeats than the Late-HD group (F[2,289] = 4.66; p = 0.01).
Known groups validity and reliability
As expected, the Neuro-QoL Social Health measures significantly distinguished between the three HD groups at each time-point and test-retest reliability was very good (Table 2).
Table 2.
Descriptive information for the Neuro-QoL Social Function Measures
| Neuro-QoL Measure | Baseline |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Premanifest |
Early-HD |
Late-HD |
Total |
F-value | Np2 | Test-Retest* | |||||
| n | M (SD) | n | M (SD) | n | M(SD) | N | M (SD) | ||||
| Ability to Participate in SRA CATa,b,c | 151 | 51.29 (8.21) | 147 | 48.18 (7.73) | 57 | 42.56 (7.48) | 355 | 48.60 (8.43) | 38.89 | 0.14 | 0.82 |
| Ability to Participate in SRA SFa,b,c | 152 | 52.28 (8.22) | 149 | 49.11 (8.28) | 57 | 42.68 (7.05) | 358 | 49.43 (8.69) | 48.93 | 0.17 | 0.85 |
| Satisfaction with SRA CATa,b,c | 151 | 51.61 (8.28) | 146 | 48.84 (7.91) | 57 | 43.94 (7.14) | 354 | 49.23 (8.36) | 28.62 | 0.11 | 0.86 |
| Satisfaction with SRA SFa,b,c | 152 | 50.16 (6.61) | 149 | 47.39 (6.00) | 57 | 45.16 (6.35) | 358 | 48.21 (6.56) | 22.91 | 0.09 | 0.87 |
| Month 12 Premanifest |
Early-HD | Late-HD | Total | F-value | Np2 | Test-Retest* | |||||
| n | M (SD) | n | M (SD) | n | M (SD) | N | M (SD) | ||||
| Ability to Participate in SRA CATa,b,c | 135 | 52.74 (8.61) | 134 | 47.23 (7.57) | 55 | 43.31 (6.26) | 324 | 48.86 (8.57) | 33.31 | 0.17 | N/A |
| Ability to Participate in SRA SFa,b,c | 135 | 52.60 (8.05) | 134 | 47.67 (7.23) | 55 | 42.41 (6.28) | 324 | 48.83 (8.28) | 39.44 | 0.20 | N/A |
| Satisfaction with SRA CATa,b,c | 135 | 52.30 (8.67) | 134 | 48.37 (8.11) | 55 | 44.56 (7.47) | 324 | 49.36 (8.69) | 18.88 | 0.11 | N/A |
| Satisfaction with SRA SFa,b | 135 | 49.88 (6.68) | 134 | 47.10 (5.73) | 55 | 44.81 (5.91) | 324 | 47.87 (6.44) | 14.99 | 0.09 | N/A |
| Month 24 Premanifest |
Early-HD | Late-HD | Total | F-value | Np2 | Test-Retest* | |||||
| n | M (SD) | n | M (SD) | n | M (SD) | N | M (SD) | ||||
| Ability to Participate in SRA CATa,b,c | 126 | 51.66 (8.81) | 122 | 41.78 (4.91) | 37 | 41.78 (4.91) | 285 | 48.31 (8.37) | 27.64 | 0.16 | N/A |
| Ability to Participate in SRA SFa,b,c | 126 | 51.47 (8.26) | 122 | 46.84 (7.93) | 37 | 42.51 (5.50) | 285 | 48.32 (8.39) | 22.61 | 0.14 | N/A |
| Satisfaction with SRA CATa,b,c | 126 | 52.35 (8.62) | 122 | 47.65 (7.81) | 37 | 43.15 (6.07) | 285 | 49.14 (8.58) | 22.68 | 0.14 | N/A |
| Satisfaction with SRA SFa,b,c | 126 | 50.83 (7.12) | 122 | 46.53 (5.86) | 37 | 43.34 (4.16) | 285 | 48.02 (6.82) | 26.40 | 0.16 | N/A |
CAT, Computer Adaptive Test; SF, Short Form; All measures had significant group differences (p < 0.0001).
Premanifest significantly differs from Early.
Premanifest significantly differs from Late.
Early significantly differs from Late.
Test-retest reliability was assessed using Intraclass Correlation Coefficient (ICC; criterion ≥0.70).
Longitudinal responsiveness
Responsiveness of HRQOL social function measures was generally as hypothesized (Table 3); SRMs for the health decline groups were generally small while SRMs for the no change/improvement group were negligible. Contrary to expectations, from baseline to 12 months the CAT administrations of Ability to Participate in SRA and for Satisfaction with SRA had negligible effect sizes for self-reported declines; the CAT administration of Ability to Participate in SRA CAT also exhibited negligible change for participants with clinician-rated declines. From 12- to 24-months, contrary to hypotheses, the Satisfaction with SRA Short change was negligible for participants with self-reported declines and change for the Ability to Participate in SRA CAT was negligible for participants with clinician-rated declines. For baseline to 24-month change, hypotheses were supported for self-reported change—both declines and no change/improvements—for all measures, as well as for clinician-rated change; except for Ability to Participate in SRA CAT, for which the effect size was negligible.
Table 3.
Standardized Response Mean (SRM) Effect Sizes
| Neuro-QoL measures | Baseline to 12 Month |
12 Month to 24 Month |
Baseline to 24 Month |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Same | Same | Same | Decline | Same | Same | Same | Decline | Same | Same | Same | Decline | |
| n | SRM | n | SRM | n | SRM | n | SRM | n | SRM | n | SRM | |
| Self-Reported Changes in Social Health (from social health anchor items) | ||||||||||||
| Social Relationships Anchor a | ||||||||||||
| Ability to Participate in SRA CAT | 274 | 0.02 | 44 | −0.12 | 224 | −0.08 | 29 | −0.26 | 232 | −0.03 | 12 | −0.35 |
| Ability to Participate in SRA SF | 276 | −0.06 | 44 | −0.4 | 224 | −0.09 | 29 | −0.39 | 234 | −0.12 | 12 | −0.69 |
| Satisfaction with SRA CAT | 271 | 0.02 | 43 | −0.22 | 216 | 0.01 | 38 | −0.41 | 231 | −0.02 | 11 | −0.53 |
| Satisfaction with SRA SF | 274 | −0.04 | 43 | −0.4 | 216 | 0.08 | 38 | −0.26 | 234 | 0.00 | 11 | −0.98 |
| Social Activities Anchor b | ||||||||||||
| Ability to Participate in SRA CAT | 261 | 0.05 | 55 | −0.22 | 208 | −0.06 | 46 | −0.31 | 225 | −0.01 | 18 | −0.48 |
| Ability to Participate in SRA SF | 263 | −0.03 | 55 | −0.44 | 208 | −0.06 | 46 | −0.46 | 227 | −0.10 | 18 | −0.59 |
| Satisfaction with SRA CAT | 266 | 0.03 | 48 | −0.14 | 214 | −0.01 | 40 | −0.31 | 224 | 0.01 | 17 | −0.60 |
| Satisfaction with SRA SF | 269 | −0.05 | 48 | −0.26 | 214 | 0.07 | 40 | −0.15 | 227 | 0.03 | 17 | −0.50 |
| Clinician-Rated Changes in Function (from TFC-based anchor) | ||||||||||||
| Ability to Participate in SRA CAT | 206 | −0.03 | 48 | −0.13 | 213 | −0.05 | 40 | −0.06 | 239 | −0.04 | 42 | −0.03 |
| Ability to Participate in SRA SF | 209 | −0.11 | 48 | −0.35 | 216 | −0.1 | 40 | −0.46 | 242 | −0.08 | 42 | −0.48 |
| Satisfaction with SRA CAT | 205 | 0.04 | 48 | −0.28 | 212 | 0.04 | 40 | −0.31 | 238 | 0.07 | 42 | −0.44 |
| Satisfaction with SRA SF | 209 | 0.04 | 48 | −0.22 | 216 | 0.05 | 40 | −0.35 | 242 | 0.03 | 42 | −0.21 |
NQoL, Neuro-QoL; CAT, Computer Adaptive Test; SF, Short Form; higher scores indicate better HRQOL; bolding indicates effects size magnitudes that are consistent with proposed hypotheses. SRM Effect Sizes: |<0.20| = Negligible; |0.20–0.49| = Small; |0.50–0.79| = Medium; |≥0.80| = Large.
For Ability to Participate in SRA: “Since the last time I filled out this questionnaire … my social relationships (including those with family, friends, and coworkers) are:” For Satisfaction with SRA: “Since the last time I filled out this questionnaire … my satisfaction with my social relationships is … ”;
For Ability to Participate in SRA: “Since the last time I filled out this questionnaire: my level of social activities is:” For Satisfaction with SRA: “Since the last time I filled out this questionnaire: my satisfaction with my social activities is: … ”
Responsiveness to change over time
While there was mixed support for 24-month change, baseline to 12-month change was generally not consistent with the proposed hypotheses (Table 4 and Fig. 1). From baseline to 12-months, the only significant changes in HRQOL for the group with self-reported declines in health were for the Ability to Participate in SRA Short Form (for social relationships, social activities, and clinician-rated anchors) and Satisfaction with SRA Short Form (for social relationships anchor). From 12- to 24-months, the only significant changes for the group with self-reported declines was for Satisfaction with SRA CAT (social relationships anchor) and Ability to Participate in SRA Short Form (social activities anchor). From baseline to 24-months, findings were more consistent with hypotheses: there were significant changes for the Ability to Participate in SRA Short Form (social activities anchor and clinician-rated function) and Satisfaction with SRA CAT (clinician-rated function) for those with self-reported declines, and there were also significant changes for Ability to Participate in SRA (SF) and Satisfaction with SRA (CAT and SF) for those with clinician-rated declines. Overall, 75% of hypotheses were supported for all measures across time-comparisons, with the exception of Ability to Participate in SRA (CAT only), which did not meet expectations for any of the time comparisons (Table 5).
Table 4.
Responsiveness to change over time relative to self-reported changes in health and clinician-rated changes in function
| Baseline to 12 Month |
12 Month to 24 Month |
Baseline to 24 Month |
||||
|---|---|---|---|---|---|---|
| Declines in | No Change/ | Declines in | No Change/ | Declines in | No Change/ | |
| Function Least squared mean (SE) | Improvement in Function Least squared mean (SE) | Function Least squared mean (SE) | Improvement in Function Least squared mean (SE) | Function Least squared mean (SE) | Improvement in Function Least squared mean (SE) | |
| Self-Reported Social Relationships Anchora | ||||||
| Ability to Participate in SRA CAT | −0.84 (1.23) | 0.19 (0.49) | −1.52 (1.54) | −0.77 (0.55) | −2.92 (2.59) | −0.29 (0.59) |
| Ability to Participate in SRA SF | −2.48 (0.97)* | −0.38 (0.39) | −1.49 (1.22) | −0.76 (0.43) | −5.08 (2.19)* | −0.87 (0.49) |
| Satisfaction with SRA CAT | −1.55 (1.06) | 0.12 (0.42) | −2.56 (1.14)* | −0.06 (0.48) | −3.01 (2.19) | −0.16 (0.48) |
| Satisfaction with SRA SF | −2.21 (0.87)* | −0.25 (0.35) | −1.20 (0.94) | 0.32 (0.39) | −2.92 (1.79) | 0.01 (0.39) |
| Self-Reported Social Activities Anchorb | ||||||
| Ability to Participate in SRA CAT | −1.53 (1.09) | 0.45 (0.50) | −1.53 (1.20) | −0.56 (0.57) | −2.11 (2.02) | −0.07 (0.59) |
| Ability to Participate in SRA SF | −2.90 (0.86)* | −0.16 (0.39) | −1.90 (0.95)* | −0.57 (0.45) | −4.57 (1.76)* | −0.78 (0.51) |
| Satisfaction with SRA CAT | −0.98 (0.99) | 0.24 (0.42) | −1.88 (1.09) | −0.19 (0.48) | −3.69 (1.75)* | 0.04 (0.48) |
| Satisfaction with SRA SF | −1.58 (0.82) | −0.27 (0.35) | −0.69 (0.90) | 0.26 (0.39) | −3.01 (1.44)* | 0.18 (0.39) |
| Clinician-Rated Changes in Function (for TFC-based Anchor) | ||||||
| Ability to Participate in SRA CAT | −0.70 (1.02) | 0.21 (0.51) | −1.55 (1.32) | −0.63 (0.56) | −0.26 (1.41) | −0.38 (0.59) |
| Ability to Participate in SRA SF | −1.88 (0.81)* | −0.44 (0.40) | −1.81 (1.05) | −0.65 (0.45) | −3.70 (1.21)* | −0.59 (0.50) |
| Satisfaction with SRA CAT | −1.18 (0.87) | 0.29 (0.44) | −1.72 (1.13) | −0.12 (0.48) | −3.07 (1.10)* | 0.48 (0.46) |
| Satisfaction with SRA SF | −0.73 (0.72) | −0.48 (0.36) | −1.73 (0.93) | 0.50 (0.40) | −1.28 (0.91) | 0.18 (0.38) |
Denotes that change significantly differs from 0 (p < .05); Higher scores indicate better HRQOL;
For Ability to Participate in SRA: “Since the last time I filled out this questionnaire … my social relationships (including those with family, friends, and coworkers) are:” For Satisfaction with SRA: “Since the last time I filled out this questionnaire … my satisfaction with my social relationships is … ”;
For Ability to Participate in SRA: “Since the last time I filled out this questionnaire: my level of social activities is:” For Satisfaction with SRA: “Since the last time I filled out this questionnaire: my satisfaction with my social activities is … ”
Fig. 1.
(A) Change over time for the group with self-reported declines versus those with no change or improvements in social health according to the social relationships anchor. (B) Change over time for the group with self-reported declines versus those with no change or improvements in social health according to the social activities anchor. (C) Change over time for the group with clinician-rated declines versus those with no change or improvements in social health according to TFC scores. Figure 1 shows 12-month change scores (for both baseline to 12-months and 12- to 24-months) for the PROMIS Social Health measures. Change scores are shown for: self-reported (A and B) and clinician-rated (C) groups (those with no decline versus those with improvements in social health), and for computer adaptive test (CAT) and short form administrations of the measures. The groups shown in (A) are relative to self-reported responses on the social relationships anchor, “Since the last time I filled out this questionnaire … my social relationships (including those with family, friends, and coworkers) are: [Much Worse, Worse, About the Same, Better, Much Better];” groups were dichotomized as follows: Much Worse or Worse = Health Declines and About the Same, Better, or Much Better = No Change/Improvement. The groups shown in (B) are relative to self-reported responses on the social activities anchor, “Since the last time I filled out this questionnaire: my level of social activities is: [Much Worse, Worse, About the Same, Better, Much Better];” groups were dichotomized as follows: Much Worse or Worse = Health Declines and About the Same, Better, or Much Better = No Change/Improvement. The groups shown in (C) are relative to clinician-rated changes using scores on the TFC from the UHDRS; groups were dichotomized as follows: those with TFC scores that got worse at follow-up and those with no change or improvements in TFC at follow-up.
Table 5.
Summary of findings for HRQOL measures relative to self-reported changes in physical HRQOL
| Significant group differences among premanifest, early- and late-HD | Test Retest ICC (≥0.70) | SRMs for Self-Reported Changes in Social Health (from anchor items) |
Clinician-Rated Change in Function (from TFC scores) |
Criterion met for responsiveness (75% of analyses consistent with proposed hypotheses) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Larger effect sizes for those with worsening health relative to those with no change/ improvement for at least one anchor (either Social Relationships or Social Activities) | Non-negligible effect sizes for the group with self-reported declines in social health for at least one anchor (either Social Relationships or Social Activities; SRMs ≤−0.20 or ≥0.20) | Negligible effect sizes for those with no change or self-reported improvements in social health for at least one anchor (either Social Relationships or Social Activities; SRMs −0.19 to 0.19) | Responsive to change for persons with self-reported declines in health for at least one anchor (either Social Relationships or Social Activities) | Larger effect sizes for those with clinician-rated declines in function health relative to those with no change/improvement | Non-negligible effect sizes for the group with clinician–rated declines in function (SRMs ≤−0.20 or ≥0.20) | Negligible effect sizes for those with no change or clinician-rated improvement in function (SRMs −0.19 to 0.19) | Responsive to change for persons with clinician rated declines in health | ||||
| Baseline to 12 Months | |||||||||||
| Ability to Participate in SRA CAT | X | X | X | X | X | X | X | ||||
| Ability to Participate in SRA SF | X | X | X | X | X | X | X | X | X | X | X |
| Satisfaction with SRA CAT | X | X | X | X | X | X | X | X | X | ||
| Satisfaction with SRA SF | X | X | X | X | X | X | X | X | X | X | |
| 12 Month to 24 Month | |||||||||||
| Ability to Participate in SRA CAT | X | X | X | X | X | X | X | ||||
| Ability to Participate in SRA SF | X | X | X | X | X | X | X | X | X | X | |
| Satisfaction with SRA CAT | X | X | X | X | X | X | X | X | X | X | |
| Satisfaction with SRA SF | X | X | X | X | X | X | X | X | X | ||
| Baseline to 24 Month | |||||||||||
| Ability to Participate in SRA CAT | X | X | X | X | X | X | |||||
| Ability to Participate in SRA SF | X | X | X | X | X | X | X | X | X | X | X |
| Satisfaction with SRA CAT | X | X | X | X | X | X | X | X | X | X | X |
| Satisfaction with SRA SF | X | X | X | X | X | X | X | X | X | X | |
X, hypothesis supported; TFC, total functional capacity.
DISCUSSION
This report provides support for the longitudinal validity of two patient-reported outcome measures from the Neuro-QoL measurement system: Ability to Participate in SRA and Satisfaction with SRA. We examined both the CAT and the short form administrations of these social health measures. We found evidence of “known groups validity,” which means that persons with greater disease burden reported more problems with social health than those at earlier stages in the disease process. Test-retest reliability was strong. The scales exhibited expected changes in longitudinal responsiveness relative to self-reported social health change. Given that establishing the clinical utility of patient-reported outcomes (PROs; e.g., reliability, validity, and responsiveness) is an ongoing process and that support for any one analysis—in any particular sample—is less important than the cumulative picture across multiple analyses and samples [29, 30], our a priori criterion to support measurement responsiveness was that at least 75% of the analyses would be consistent with the proposed hypotheses.
Both the CAT and short forms versions of the Neuro-QoL Social Health measures were able to distinguish between persons with HD who are premanifest, early-stage, and late-stage. Persons with late-stage HD reported worse social health than either of the other two groups, and that those with early-stage HD reported worse social health than persons with premanifest HD. In addition, test-retest reliability was very good for all measures. Twelve month and 24-month responsiveness was generally supported relative to the self-reported anchors, but generally not supported relative to clinician-rated change. Although the pattern of results was not fully concordant with our proposed hypotheses, these findings are not especially surprising given that we would expect self-reported changes in social health to track better with self-reported responses on the Neuro-QoL Social Health measures than we would for clinician-rated change in functioning.
Findings provided support for the clinical utility of these measures with the exception of the CAT administration format of Ability to Participate in SRA. Given that the SF administration of this same measure did meet the a priori criterion, this would suggest that calibration data for this measure (which is based on both the general population and persons with other neurological conditions [not HD]) might not be appropriate for use in persons with HD. As such, this finding highlights the importance of disease-specific validation of new assessment measures and the potential need for future efforts to recalibrate this measure in persons with HD. Given these findings, we would recommend that, for studies of HD groups, persons wishing to administer the Ability to Participate in SRAs use the SF in future studies, until further study of the CAT performance can be done.
This study exhibited several strengths. First, the Neuro-QoL Social Health measures were administered to a large representative sample of individuals across the HD disease spectrum. Second, given that social health is an important component of HRQOL, this study provides important data to support the clinical utility of a brief PRO that could easily be implemented in existing studies to gather more information about this important construct in persons with HD. Study weaknesses include the absence of a well-matched clinician-reported or observer-rated anchor of social health, as well as other objective data about patient social health. Furthermore, the sample was primarily Caucasian, and participants were well-educated, limiting the generalizability of findings to ethnic/racial minorities and persons with HD that are less well educated.
In conclusion, these study findings provide support for the validity and responsiveness of the Neuro-QoL Ability to Participate in SRA SF, as well as both the CAT and SF administrations of Neuro-QoL Satisfaction with SRA in persons with premanifest and manifest HD. It is our hope that these findings encourage clinicians and researchers to consider this important construct in both their clinical research, as well as in their clinical care, and that future work is focused on the development of interventions designed to foster social participation and community engagement in these individuals.
Supplementary Material
ACKNOWLEDGMENTS
Work on this manuscript was supported by the National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (R01NS077946) and the National Center for Advancing Translational Sciences (UL1TR000433). In addition, a portion of this study sample was collected in conjunction with the Predict-HD study. The Predict-HD study was supported by the NIH, National Institute of Neurological Disorders and Stroke (R01NS040068), the NIH, Center for Inherited Disease Research (provided supported for sample phenotyping), and the CHDI Foundation (award to the University of Iowa).
We thank the University of Iowa, the Investigators and Coordinators of this study, the study participants, the National Research Roster for Huntington Disease Patients and Families, the Huntington Study Group, and the Huntington’s Disease Society of America. We acknowledge the assistance of Jeffrey D. Long, Hans J. Johnson, Jeremy H. Bockholt, Roland Zschiegner, and Jane S. Paulsen. We also acknowledge Roger Albin, Kelvin Chou, and Henry Paulsen for the assistance with participant recruitment. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
HDQLIFE Site Investigators and Coordinators: Noelle Carlozzi, Praveen Dayalu, Stephen Schilling, Amy Austin, Matthew Canter, Siera Goodnight, Jennifer Miner, Nicholas Migliore (University of Michigan, Ann Arbor, MI); Jane Paulsen, Nancy Downing, Isabella DeSoriano, Courtney Shadrick, Amanda Miller (University of Iowa, Iowa City, IA); Kimberly Quaid, Melissa Wesson (Indiana University, Indianapolis, IN); Christopher Ross, Gregory Churchill, Mary Jane Ong (Johns Hopkins University, Baltimore, MD); Susan Perlman, Brian Clemente, Aaron Fisher, Gloria Obialisi, Michael Rosco (University of California Los Angeles, Los Angeles, CA); Michael McCormack, Humberto Marin, Allison Dicke (Rutgers University, Piscataway, NJ); Joel Perlmutter, Stacey Barton, Shineeka Smith (Washington University, St. Louis, MO); Martha Nance, Pat Ede (Struthers Parkinson’s Center); Stephen Rao, Anwar Ahmed, Michael Lengen, Lyla Mourany, Christine Reece, (Cleveland Clinic Foundation, Cleveland, OH); Michael Geschwind, Joseph Winer (University of California – San Francisco, San Francisco, CA), David Cella, Richard Gershon, Elizabeth Hahn, Jin-Shei Lai (Northwestern University, Chicago, IL).
Footnotes
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
SUPPLEMENTARY MATERIAL
The supplementary material is available in the electronic version of this article: http://dx.doi.org/10.3233/JHD-190385.
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