The National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS®) is a standardized set of patient-reported outcomes (PROs) that cover physical, mental, and social health. The aim of this study was to develop the NIH PROMIS gastrointestinal (GI) symptom measures.
We first conducted a systematic literature review to develop a broad conceptual model of GI symptoms. We complemented the review with 12 focus groups including 102 GI patients. We developed PROMIS items based on the literature and input from the focus groups followed by cognitive debriefing in 28 patients. We administered the items to diverse GI patients (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), systemic sclerosis (SSc), and other common GI disorders) and a census-based US general population (GP) control sample. We created scales based on confirmatory factor analyses and item response theory modeling, and evaluated the scales for reliability and validity.
A total of 102 items were developed and administered to 865 patients with GI conditions and 1,177 GP participants. Factor analyses provided support for eight scales: gastroesophageal reflux (13 items), disrupted swallowing (7 items), diarrhea (5 items), bowel incontinence/soilage (4 items), nausea and vomiting (4 items), constipation (9 items), belly pain (6 items), and gas/bloat/flatulence (12 items). The scales correlated significantly with both generic and disease-targeted legacy instruments, and demonstrate evidence of reliability.
Using the NIH PROMIS framework, we developed eight GI symptom scales that can now be used for clinical care and research across the full range of GI disorders.
Five core domains have been endorsed by Outcomes Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. The aim of this work was to evaluate instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination.
A systematic search strategy for instruments used to measure the acute gout core domains was formulated. For each method, articles were assessed by two reviewers to summarise information according to the specific components of the OMERACT filter.
Seventy-seven articles and abstracts met the inclusion criteria. Pain was most frequently reported (76 studies, 20 instruments). The pain instruments used most often were 100mm visual analog scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face and content validity, within- and between-group discrimination. Four-point Likert scales assessing index joint swelling and tenderness have been used in numerous acute gout studies; these instruments are feasible, with high face and content validity, and show within- and between-group discrimination. Five-point patient global assessment of response to treatment (PGART) scales are feasible and valid, and show within- and between-group discrimination. Measures of activity limitations were infrequently reported, and insufficient data were available to make definite assessments of the instruments for this domain.
Many different instruments have been used to assess the acute gout core domains. Pain VAS and 5-point Likert scales, 4-point Likert scales of index joint swelling and tenderness and 5-point PGART instruments meet the criteria for the OMERACT filter.
gout; pain; measurement; outcome
Systemic sclerosis (SSc) is associated with a marked economic burden, high treatment costs and decreased productivity. Although treatment strategies for SSc can have a substantial effect on patients’ outcomes, it is not known whether patients with SSc consistently receive such care. Evaluation of process-of-care quality requires specification of quality indicators (QIs), clinically detailed statements of the eligible patients and the care they should receive to achieve a minimal level of quality of care. Our objective was to develop QIs for patients with SSc.
We performed a comprehensive literature review of diagnosis and treatment of SSc and proposed QIs that were evaluated by a national Expert Panel (n=9) who were asked to review the supporting literature and individually rank the validity of each QI. These rankings formed the basis of discussion at a face-to-face meeting following the RAND/UCLA method to integrate expert opinion with literature review to identify a set of final QIs. We then presented these QIs to members of the Scleroderma Clinical Trials Consortium (SCTC).
Thirty-two QIs for SSc care were judged valid by the Expert Panel. The QI set includes 9 QIs for newly diagnosed with SSc, 12 follow-up QIs for management of SSc, and 11 treatment QIs. The SCTC experts agreed with the validity of each of the 32 QI and agreed that for all but one QI the specified tests, procedures and treatments recommended in the QI were generally available.
We have developed 32 QIs for SSc using a rigorous methodology that can be employed to evaluate and improve care for patients with SSc, as well as inform policy decisions supporting appropriate care for SSc patients.
Systemic sclerosis; quality indicator
To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10).
During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9.
One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure.
With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group.
PATIENT-REPORTED OUTCOMES; CHRONIC GOUT; VALIDATION; PAIN; PATIENT GLOBAL; FUNCTIONAL LIMITATION
NSAIDs; COX-2 inhibitor; colchicine; corticosteroid therapy; prednisone; intra-articular glucocorticosteroids; ACTH; anakinra; canakinumb; rilonacept; IL-1
Allopurinol; Febuxostat; Probenecid; Pegloticase; Uricosuric; Xanthine Oxidase; Tophi
The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Roadmap initiative is a cooperative group program of research designed to develop, evaluate, and standardize item banks to measure patient-reported outcomes relevant across medical conditions. For adults, 11 domains have been developed in physical, mental, and social health.
The objective of the current study was to assess feasibility and construct validity of PROMIS item banks versus legacy measures in a observational study in systemic sclerosis (SSc).
Patients with SSc in a single academic center completed computerized adaptive technology (CAT) administered PROMIS item banks during the clinic visit and legacy domains (using paper-and-pencil). The construct validity of PROMIS items was evaluated by examining correlations with corresponding legacy measures using multitrait-multimethod analysis.
Participants consisted of 143 SSc patients with an average age of 51.5 years; 71% were female and 68% were Caucasian. The average number of items completed for each CAT-administered item bank ranged from 5 to 8 (69 CAT items per patient), and the average time to complete each CAT-administered item bank ranged from 48 seconds to 1.9 minutes per patient (average time= 11.9 minutes/per patient for 11 banks). All correlations between PROMIS domains and respective legacy measures were large and in the hypothesized direction (ranged from .61 to .82).
Our study supports the construct validity of the CAT-administered PROMIS item banks and shows that they can be administered successfully in a clinic with support staff. Future studies should assess the feasibility of PROMIS item banks in a busy clinical practice
Systemic sclerosis; PROMIS; health-related quality of life; construct validity
The prevalence of gout is increasing, and most research on the associated burden has focused on serum urate (sUA) levels. The present study quantifies the impact of the presence of tophi and frequency of acute gout attacks on health-related quality of life (HRQOL), productivity, and healthcare resource utilization.
Patients with self-reported gout (n = 620; 338 in US and 282 across France, Germany, and UK) were contacted based on inclusion in the 2010 US and EU National Health and Wellness Surveys (Kantar Health) and the Lightspeed Research ailment panel. Respondents were categorized into mutually-exclusive groups based on number of gout flares experienced in the past 12 months (0/don’t recall, 1–2, 3, 4–5, 6+), current presence of tophi (none, 1+, or not sure), and sUA level awareness (yes, no). HRQOL (SF-12v2), healthcare provider visits in the last 6 months, and work productivity and activity impairment (WPAI) were compared across groups.
Most patients were males, mean age of 61 years, who reported experiencing at least one acute gout flare in the past 12 months, and 12.3% (n = 76) reported presence of tophi. Among the 27.7% (n = 172) of patients who were aware of their sUA levels, higher sUA was associated with more flares and tophi. Decreased HRQOL was associated with more frequent flares and presence of tophi. In multivariable models predicting outcomes based on presence of tophi and number of flares, both flares (≥4) and tophi (≥1) were associated with HRQOL decrements on physical and mental component summary scores and health utilities (all p < 0.05), after adjustment for age, gender, and time since diagnosis. Flares were also associated with greater activity impairment.
Impairments associated with gout flares and presence of tophi, across patients in the US and EU, underscore the importance of effective management of this potentially curable condition.
Gout; Quality of life; Productivity; Refractory chronic gout
Objective. The Gout Impact Scale (GIS) is a gout-specific quality of life instrument that assesses impact of gout during an attack and impact of overall gout. The GIS has five scales and each is scored from 0 to 100 (worse health). Our objective was to assess minimally important differences (MIDs) for the GIS administered in a randomized controlled trial (RCT) assessing rilonacept vs placebo for prevention of gout flares during initiation of allopurinol therapy.
Methods. Trial subjects ( n = 83) included those with two or more gout flares (self-reported) in the past year. Of these, 73 had data for Weeks 8 vs 4 and formed the MID analysis group and were analysed irrespective of the treatment assignment. Subjects completed the GIS and seven patient-reported anchors. Subjects with a one-step change (e.g. from very poor to poor) were considered as the MID group for each anchor. The mean change in GIS scores and effect size (ES) was calculated for each anchor’s MID group. The average of these created the overall summary MID statistics for each GIS. An ES of 0.2–0.5 was considered to represent MID estimates.
Results. Trial subjects (n = 73) were males (96.0%), White (90.4%), with mean age of 50.5 years and serum uric acid of 9.0 mg/dl. The mean change score for the MID improvement group for scales ranged from −5.24 to −7.61 (0–100 scale). The ES for the MID improvement group for the four scales ranged from 0.22 to 0.38.
Conclusion. The MID estimates for GIS scales are between 5 and 8 points (0–100 scale). This information can aid in interpreting the GIS results in future gout RCTs.
Trial Registration. Clinicaltrials.gov, www.clinicaltrials.gov, NCT00610363.
Gout assessment questionnaire; Gout impact scale; Minimally important difference; Minimal clinically important differences; Rilonacept; Clinical trial design; Health-related quality of life; Health status
Objective. Short Form-36 (SF-36) is a validated outcome measure to assess health-related quality of life (HRQOL) in patients with gout. We assessed responsiveness to change of SF-36 in patients with gout.
Methods. SF-36 was administered at baseline and at yearly intervals. We assessed the minimal clinically important differences (MCIDs) at the first and second year. We also assessed the responsiveness to change (effect size) and interpreted it based on Cohen’s criteria. We modelled the improvement (defined as ≥MCID) in SF-36 scales and summary scores. Covariates included age, presence of tophi, comorbidities, baseline joint involvement, baseline serum urate, change in serum urate and the number of flares from baseline to 12 months.
Results. Of 99 subjects, 96 were male, mean age was 57.1 years, disease duration was 8.2 years and 40.4% had tophi. Ninety-two patients were treated with urate-lowering therapy (ULT) and daily colchicine, and seven were only on colchicine. Baseline mean serum urate level was 8.9 mg/dl and mean number of flares was 4.7 over last year. ULTs were associated with reduction in serum uric acid and number of flares (P < 0.001 for both) over 12 months. Therapy was associated with 22–70% of the patients achieving MCID in SF-36 scores at 12 months. Effect size estimates ranged from negligible to large (SF-36 mental component summary 0.08–bodily pain 1.09). Reduction in flares independently predicted improvements in three SF-36 physical scales (P = 0.001–0.06). Improvement in SF-36 scores was maintained at 2 years.
Conclusion. In our real-life observational cohort, chronic urate lowering therapy and colchicine was associated with clinically meaningful improvements in HRQOL at 1 year and then maintained at 2 years. SF-36, especially physical domains and physical component summary, are responsive to change in gout.
Gout; Health-related quality of life; Quality of life; Flares; Urate-lowering therapy; Minimal clinically important differences; Minimally important differences; Short Form-36, Gout prophylaxis
Objective. Although the incidence of dcSSc is higher in African-American and Hispanic populations compared with European Caucasian patients, it is not clear whether there are differences in subsequent disease course. Also, the potential impact of gender on the disease course of dcSSc is not well defined. Our objective was to assess the course of modified Rodnan skin score (MRSS), HAQ-disability index (HAQ-DI) and forced vital capacity per cent (FVC%) predicted between men vs women and three ethnic groups with dcSSc participating in three randomized clinical trials (RCTs).
Method. Data from RCTs (n = 495) were pooled and analysed. Baseline characteristics were compared in men vs women and among ethnic groups. A linear mixed effects model was used to assess the predictors of MRSS, HAQ-DI and FVC%. The primary independent variables were time-in-study and its interaction with gender and ethnicity. The models were adjusted for other covariates that were significant at baseline between gender and ethnicity analyses.
Results. Men had lower HAQI-DI scores compared with women (P < 0.05). Among the three ethnic groups, Caucasians were older, African-Americans had lower FVC% predicted and Hispanics had greater tender joint counts (P < 0.05). The course of MRSS, HAQ-DI and FVC% predicted during the study period was not significantly different between gender and three ethnicities. Time-in-study was an independent predictor of improvement in MRSS and HAQ-DI.
Conclusion. Our analysis explores the influence of gender and ethnicity on disease course in RCTs. These findings are relevant to issues of future trial design.
Scleroderma; Randomized clinical trial; Clinical trials; Systemic sclerosis; Gender; Race; Ethnicity; Diffuse cutaneous systemic sclerosis
Fatigue is a common symptom in RA and used as an outcome measure in RA clinical trials. We studied a large academic clinical practice to estimate the minimally important difference (MID) for a fatigue visual analog scale using patient-reported anchors (fatigue, pain and overall health).
RA patients (N=307) had clinic visits at 2 time points at a median of 5.9 months apart. They completed fatigue visual analog scale (VAS; 0–10) and retrospective anchor items, “How would you describe your overall fatigue/pain/overall health since the last visit?” Much worsened, Somewhat worsened, Same, Somewhat better, or Much better. The fatigue anchor was used for primary analysis and the pain/ overall health anchors for sensitivity analyses. The minimally changed group was defined by those reporting they were somewhat better or somewhat worsened.
The mean (SD) age was 59.4 (13.2) years, disease duration was 14.1 (11.5) years, and 83% of patients were women. The baseline mean (SD) HAQ-DI score was 0.84 (0.75). The baseline fatigue VAS score was 4.2 (2.9) and at follow up was 4.3 (2.8) (mean change of −0.07 [2.5], p=NS). The fatigue change score (0–10 scale) for somewhat better and somewhat worsened for fatigue anchor averaged −1.12 and 1.26, respectively. Using pain anchor, the fatigue changed score for somewhat better and somewhat worsened averaged −0.87 and 1.13 and using global anchor, the fatigue changed score for somewhat better and somewhat worsened averaged −0.82 and 1.17, respectively.
Effect size (ES) estimates using 3 anchors were small for somewhat better (range: 0.27 to 0.39) and somewhat worsened (range: 0.40 to 0.44) groups but larger than the no-change group (range: 0.03 to 0.08).
The MID for fatigue VAS is between −0.82 to −1.12 for improvement and 1.13 to 1.26 for worsening on 0–10 scale in a large RA clinical practice and similar to that seen in RA clinical trials. This information can aid in interpreting fatigue VAS in day-to-day care in clinical practice.
Minimally important differences; Minimal clinically important differences; rheumatoid arthritis; fatigue; visual analog scale; reliable change index; clinical practice
Objectives. To characterize the baseline tendon friction rubs (TFRs) in early dcSSc and to evaluate the association of change in TFR over 6 and 12 months with changes in modified Rodnan skin score (MRSS) and HAQ-Disability Index (HAQ-DI) over 12 and 24 months, respectively.
Methods. We analysed data from the d-Pen study, a 2-year study in early dcSSc (⩽18 months from first non-Raynaud’s symptom). TFR was scored as present/absent at seven anatomical sites at baseline and every 6 months thereafter. Multivariable linear regression models assessed associations between TFR and change in MRSS, and change in the HAQ-DI, over 12 and 24 months, respectively. Covariates included baseline TFR, change in the TFR over 6 and 12 months, age, sex, duration of SSc, MRSS, and tender joint count and swollen joint count (SJC).
Results. Forty-nine (37%) of 134 patients had TFR at baseline, 50% had resolution of their TFR, whereas 21% developed new TFRs. Patients with baseline TFRs were likely to be Caucasian (86 vs 58%) and had a higher HAQ-DI score (P = 0.008). In regression analyses, change in TFR (P = 0.04) and baseline MRSS (P = 0.03) predicted change in MRSS over a 12-month period (Model R2 = 0.14). For the HAQ-DI model, independent predictors were change in TFR at 6 months (P = 0.008) and baseline SJC (P = 0.04, Model R2 = 0.19). Results were similar for 24-month models.
Conclusions. We document the presence of TFR very early in the course of dcSSc. Changes in TFR over 6 and 12 months predict changes in MRSS and HAQ-DI over 12 and 24 months, respectively.
Early scleroderma; Diffuse SSc; D-Penicillamine study; Tendon friction rubs; Scleroderma clinical trial
Psoriatic arthritis (PsA) and scleroderma (SSc) are chronic rheumatic disorders with detrimental effects on health-related quality of life. Our objective was to assess health values (utilities) from the general public for health states common to people with PsA and SSc for economic evaluations.
Adult subjects from the general population in a Midwestern city (N = 218) completed the SF-12 Health Survey and computer-assisted 0-100 rating scale (RS), time trade-off (TTO, range: 0.0-1.0) and standard gamble (SG, range: 0.0-1.0) utility assessments for several hypothetical PsA and SSc health states.
Subjects included 135 (62%) females, 143 (66%) Caucasians, and 62 (28%) African-Americans. The mean (SD) scores for the SF-12 Physical Component Summary scale were 52.9 (8.3) and for the SF-12 Mental Component Summary scale were 49.0 (9.1), close to population norms. The mean RS, TTO, and SG scores for PsA health states varied with severity, ranging from 20.2 to 63.7 (14.4-20.3) for the RS 0.29 to 0.78 (0.24-0.31) for the TTO, and 0.48 to 0.82 (0.24-0.34) for the SG. The mean RS, TTO, and SG scores for SSc health states were 25.3-69.7 (15.2-16.3) for the RS, 0.36-0.80 (0.25-0.31) for the TTO, and 0.50-0.81 (0.26-0.32) for the SG, depending on disease severity.
Health utilities for PsA and SSc health states as assessed from the general public reflect the severity of the diseases. These descriptive findings could have implications regarding comparative effectiveness research for tests and treatments for PsA and SSc.
Objective. The modified Rodnan skin score (MRSS) is a standard outcome measure for skin disease in SSc and calculated by summation of skin thickness in 17 different body sites (total score = 51). Our objective was to evaluate the sensitivity of change over time of individual body sites used in the calculation of total MRSS.
Methods. We analysed two randomized placebo controlled clinical trials investigating the effect of either recombinant human relaxin or type I oral collagen in dcSSc. Both trials used MRSS as the primary outcome measure. We used a change of >10 mm (on a 0–100 VAS) in the patient global assessment (PGA) as the clinically important improvement. We calculated the mean change and the effect size (ES) for each individual body site used in the total MRSS for each study. Magnitude of ES was assessed using Cohen's rule of thumb for ES.
Results. In the relaxin and collagen studies, 71 of 199 patients (36%) and 54 of 129 (42%) of patients had an improvement >10 mm on the PGA at 6 and 12 months, respectively. Total MRSS had large ES in both studies (0.85–0.98); the chest, forearms and hands had moderate ES (0.50–0.74); and the lower extremities, face, abdomen and fingers had small ES (0.16–0.49).
Conclusion. Certain body sites (hands, forearms and chest) are more sensitive to change compared with other body sites in two randomized clinical trials. It remains to be seen whether decreasing the number of body sites by exclusion of relatively static areas would further increase the sensitivity to change over time of the total MRSS.
Modified Rodnan skin score; Clinical trials; Scleroderma; Outcome measures
The Raynaud’s Condition Score (RCS) is a validated outcome measure for Raynaud’s phenomenon (RP). Our objective was to assess the minimally important difference (MID) and Patient Acceptable Symptom State (PASS) for RCS in patients with RP.
Subjects and Methods
Patients with active RP (N=162) [mean RCS > 25 (0–100 VAS)] participated in a placebo-controlled, cross over randomized clinical trial (RCT). Data from the 2 treatment groups were combined for this analysis. We administered retrospective and prospective anchors during the RCT. MID groups were defined as the group who reported being somewhat better (anchor#1) and a 1-step change from “unbearable” to “very severe” etc. (anchor#2). We considered patients as achieving PASS if they rated their Raynaud’s condition as ‘very mild’ or ‘mild’ at the last study visit.
The mean age of participants was 48.9 years and the mean baseline RCS score was 46.4. The RCS change score for the MID improvement group ranged from − 13.9 to − 14.3 points and PASS estimate was 34.0 points.
The MID and PASS estimates for RCS are 14–15 points for improvement and 34 points, respectively on a 0–100 scale in a large RCT of patients with active RP. This information can aid in interpreting RCS in future RP trials.
Systemic sclerosis; Patient Acceptable Symptom State; minimally important differences; Rayanud’s phenomenon
To assess the course of modified Rodnan skin score (MRSS) in patients with diffuse cutaneous systemic sclerosis (dcSSc) with different baseline disease durations (defined from the date of onset of first non-Raynaud’s phenomenon symptom) in 3 large randomized controlled trials (RCT).
Data from RCTs were pooled and analyzed: high dose versus low dose D-Penicillamine (D-Pen), recombinant human relaxin vs. placebo (relaxin), and oral bovine type I collagen vs. placebo (collagen) studies. Patients were divided into 5 groups according to their disease durations at baseline. The linear mixed model for correlated data was used to model the two predictors of MRSS: Time (in months) and disease duration.
At entry, mean MRSS score was 21.0 units in the D-Pen, 27.3 units in the relaxin, and 26.1 units in the collagen studies. Time in study was a significant predictor of improvement of MRSS regardless of disease duration at baseline (P-value: < 0.0001). Patients with disease duration ≥ 2 years showed a greater rate of decline compared to patients with < 2 years (P-values: < 0.05). Similar results were obtained when disease duration was reclassified by including Raynaud’s phenomenon in the definition.
Our study confirms recent findings that patients entered in the clinical trials do not follow the same trend in natural history of skin thickening as seen in the dcSSc populations previously reported in early open longitudinal studies. These findings have important implications in study design where “prevention of worsening” is the main objective.
Natural history; scleroderma; systemic sclerosis; clinical trials; modified Rodnan skin score