Abstract
Objective:
To report patient-centered outcomes and finalization of key study procedures from a 9-month pilot Internet randomized controlled trial (RCT) of cherry extract vs. diet modification.
Methods:
We randomized 84 people with physician-confirmed gout in an Internet study to cherry extract (n=41) or dietitian-assisted diet modification for gout (n=43). All study outcomes were collected via Internet and phone calls. We finalized key study procedures. We assessed acceptability and feasibility of the intervention, and satisfaction with study website.
Results:
Study participant satisfaction with the intervention was high. The intervention was perceived as easy, enjoyable, understandable, and helpful (scores 65–88 for all; higher=better). The amount of time spent for study was acceptable. Participant satisfaction with website interaction and content was very high, 85% or more were moderately to extremely satisfied. Significantly lower total calories, total carbohydrate and saturated fat intake were noted at 6-months in the diet modification vs. cherry extract group; differences were insignificant at 9-months. Six of the eight HAQ sections/domains improved significantly from baseline to 9-months in cherry extract vs. two HAQ sections/domains in the diet modification group. Key study procedures were finalized for a future trial, including an Internet diet assessment tool, gout flare assessment, provider confirmation of gout diagnosis, patient-reporting of classification criteria and centralized laboratory-assisted serum urate (SU) testing.
Conclusions:
High patient acceptability and feasibility of study/intervention and finalization of key study procedures indicates that hypothesis-testing Internet gout trials of cherry extract and/or diet modification can be conducted in the future.
Background
Gout, the most common inflammatory arthritis affecting Americans with an increasing prevalence [1], is challenging to manage despite the availability of effective urate-lowering therapy (ULT) and anti-inflammatory drugs [2]. Management is challenging due to several factors, including concomitant comorbidities, patient and physician knowledge gaps, low adherence to urate-lowering therapy (ULT) and differences between patient preferences and physician recommendations [1–5]. Many patients believe that gout is primarily caused by diet and prefer diet modification and dietary supplements (e.g. cherry extract) as alternatives to pharmacological treatment [5–8]. Patients with gout consider studies of non-pharmacological therapies to be the highest priority for research [9], yet there is a lack of trials assessing the efficacy of diet modification and dietary supplements [10]. Assessment of complementary and alternative therapies is one of the national priorities in comparative effectiveness research [11]. Evaluation of non-pharmacological gout treatments using a rigorously designed trial can address this priority.
Therefore, we designed a 9-month Internet pilot feasibility study, coMparative feasibility study IN GOUt: CHerry extract vs. diet modification (mini-GOUCH) [12]. We reported study procedure completion rates (primary outcome), effect estimates for proposed outcomes for future RCT (gout flares and function) and key secondary outcomes (serum urate, pain, adverse events [AEs]) recently [12]. The objective of this report was to describe: (1) patient-reported outcomes including acceptability and feasibility of intervention and study, diet component modification, exploratory outcomes (HAQ sections, dietary changes, current pain, well-being, satisfaction with ULT medication); and (2) finalization of key study procedures/tools including modification of an Internet diet tool modified for gout, 2-weekly gout flare surveys, confirmation of gout diagnosis by healthcare provider, patient-reporting of the gout classification criteria and the use of a centralized laboratory to obtain serum urate (SU).
Methods
Study overview, Study Sample, Patient Enrollment and Screening Using an Internet website
We built an Internet website (www.cherries4gout.com) and modified VioScreen™, a reliable and user-friendly graphical NIH-funded Food Frequency Questionnaire (FFQ) [13–15] into an Internet tool, GoutWell, that sent gout education and adherence messages (details in the results section). Patients completed study follow-up assessments every 3-months and the gout flare assessments every 2-weeks, both via the Internet surveys. Non-responders received automatic reminder emails every 24 hours for 5 days, followed by a phone follow-up to complete the surveys. Details of study screening, enrollment and follow-up were described previously [12]. All participants were recruited online. Screening, baseline and follow-up “virtual visits” were completed via using the Internet and the phone in this Internet gout study. This pilot, parallel arm, 1:1 allocation ratio, randomized trial was open-label due to the nature of the interventions.
Briefly, potential participants were invited for study enrollment from 2/2016 to 10/2016 by providing an Internet link to the study website (www.cherries4gout.com) that provided description of the study and study procedures [12]. The study was approved by UAB Institutional Review Board (IRB).
Study Inclusion criteria
Study Inclusion criteria were: (1) adults ≥ 18 years; (2) a valid current U.S. mailing address and email address; (3) patient self-reported physician diagnosis of gout, confirmed by contacting participant’s healthcare provider who also provided ACR gout classification criteria [16], as did patients. Study exclusion criteria were: patient self-reported rheumatoid arthritis or spondyloarthritis (other inflammatory arthritides often confused with gout); physician confirmation that diagnosis was not gout; and the current use of cherry extract, juice or concentrate.
Randomization and Study Intervention
We randomized participants using an online computerized permuted variable block design with simple randomization in a 1:1 ratio to either group: 1200 mg of cherry extract (3 capsules) or individualized diet modification. Each study participant received either the 3-month supply of cherry capsules, or individualized diet recommendation (based on the most recent baseline FFQ data) via certified mail at 3-, 6- and 9-months and receipt was confirmed with email or a phone call. Each participant also received either study coordinator calls to encourage cherry extract adherence or dietitian calls to discuss specific recommendations (details below).
Baseline and Follow-up Assessments
At baseline, participants completed assessments of gout flare, activity limitation with Health assessment questionnaire (HAQ; co-primary measures), diet assessment using GoutWell (an online FFQ), self-reported comorbidity index, smoking and alcohol use, AEs and ULT use. Exploratory outcomes included HAQ sections/domains, FFQ, well-being, current pain intensity and serum urate (SU). Baseline blood draw for SU was performed at a closest/most convenient Quest® laboratory site (details in the results section).
Participants completed brief online questionnaires (<30-minutes total) every 3 months at 3-, 6- and 9-months (HAQ, AEs, gout medication use, well-being), sent to their email address via a link, using their unique login and password. Gout flare questionnaires were completed via email every 2-weeks. SU blood draws were done at the nearest Quest® laboratory site at 9-months only. We invited each study participant to join group teleconference call sessions lasting 30–60 minutes either at 0-, 1-, 4, 7-months with study coordinators (cherry extract group) or 0-, 6- and 9-months with a registered dietitian (A.W., or B.D.; diet modification group).
Feasibility, Acceptability, Satisfaction, Exploratory Study outcomes and Study De-briefing
Study and intervention acceptability
Study and intervention acceptability were assessed at 9-months using validated questionnaires, adapted for our study [17, 18]. Satisfaction with website content, function and other aspects were assessed at 9-months using a structured website evaluation form.
Dietary assessments
Dietary assessments were done at 0-, 3-, 6- and 9-months using GoutWell, a modified gout-specific (inclusion of additional food items such as anchovies etc.) version of VioScreen™, an online, reliable, self-reported Food Frequency Questionnaire (FFQ) that assesses food choices and portion sizes over the past 90 days [14].
Activity limitation Assessment
Activity limitation Assessment was done with Health Assessment Questionnaire (HAQ), a validated measure, at 0-, 3-, 6- and 9-months [19–21]. HAQ assesses difficulty in 8 sections/domains (dressing, arising, eating, walking, hygiene, reaching, gripping, and outside activity) using 20 items, score for each section is calculated as the worst score within the section and ranges from 0 (without any difficulty) to 3 (unable to do), i.e. if one question is scored 1 and another 2, then the score for the section is 2. Use of an aide or device or requiring help from another individual, makes the minimum score for that section to be 2. The total score is the sum of scores of 8 sections divided by 8 and ranges from 0 (no disability) to 3 (complete disability). The minimal clinically meaningful improvement threshold for the total HAQ sore is 0.22 [22]. To our knowledge, there are no MCID thresholds for HAQ sections.
Well-being and current pain intensity
Well-being and current pain intensity were each assessed on a 0–10 scale at 0-, 3-, 6- and 9-months, with lower scores indicating better outcomes for both.
Assessment of barriers and facilitators
Assessment of barriers and facilitators to GoutWell assisted cherry extract adherence and dietary changes was performed at 9-months using a brief pre-tested semi-structured interview guide [23] at the end of the study to gain additional insights for the future hypothesis-testing trial.
Exploratory outcomes within cherry extract and diet modification groups were compared to baseline values using paired t-tests for continuous outcomes (HAQ sections, pain intensity, well-being) and McNemar’s test for categorical outcomes (target SU).
Results
Study participant characteristics
In this study, 84 participants with gout were randomized to cherry extract (n=41) and diet modification (n=43; Appendix 1; CONSORT flow chart). Since cherry extract is not a drug, biologic, or device regulated by the U.S. Food and Drug Administration (FDA), study registration was not required on clinicaltrials.gov
Patient characteristics have been previously described [12], and were similar across the study treatment arms. The study participants had a mean (standard deviation (SD)) age of 56 years (SD, 14), mean BMI was 33 kg/m2 (SD, 9), mean gout flares in the last year were 4 (SD, 5.4), i.e. 0.33 gout flares/month. Of participants, 72% were male, 68% were white, 80% had ever had some sort of gout medication prescription, and 37% were currently on ULT. Satisfaction with ULT medications at baseline was moderate and similar for cherry extract vs. diet modification. Other patient characteristics were similar between the two arms and are shown in Table 1.
Table 1.
Patient characteristics at baseline
| All participants (N=84) Mean ± SD or n (%) | Cherry extract (N=41*) Mean ± SD or n (%) | Diet modification (N=43*) Mean ± SD or or n (%) | p-value: diff between the two arms | |
|---|---|---|---|---|
| Age, Mean (± SD) | 55.8±13.9 | 58.2±15.5 | 53.6 ±11.9 | 0.13 |
| Gender, Male n (%) | 61 (72%) | 31 (76%) | 30 (70%) | 0.54 |
| Race, n (%) | 0.55 | |||
| White | 57 (68%) | 30 (73%) | 27 (63%) | |
| Black or African American | 21 (25%) | 9 (22%) | 12 (28%) | |
| Asian/Other1/mixed | 6 (7%) | 2 (5%) | 4 (9%) | |
| Pt.-reported Last uric acid level (mg/dl), mean (SD) | 7.52±3.0 | 7.14±2.6 | 7.9±3.3 | 0.39 |
| Currently taking allopurinol, febuxostat or probenecid2 | 30 (37%) | 13 (33%) | 17 (42%) | 0.40 |
| Well-being - very well to very poor (0–10; lower =better) | 2.9±2.6 | 3.1±2.83 | 2.7±2.4 | 0.55 |
| Currently on Special diet | 24 (29%) | 12 (29%) | 12 (28%) | 0.89 |
| Validated gout flare at baseline3 | 24 (29%) | 13 (32%) | 11 (26%) | 0.53 |
| Pt. reported Current gout flare: Baseline | 30 (36%) | 18 (44%) | 12 (28%) | 0.13 |
| Pt. reported warm joint | 25 (30%) | 15 (37%) | 10 (23%) | 0.18 |
| Pt. reported swollen joint | 45 (54%) | 28 (68%) | 17 (40%) | 0.008 |
| Average pain 24 hrs >=3 | 26 (31%) | 13 (32%) | 13 (30%) | 1.0 |
| Pain Intensity (0–10) | ||||
| Now | 1.92±2.7 | 2.17±2.8 | 1.67±2.5 | 0.40 |
| Average pain 24 hrs | 2.05±2.6 | 2.19 ±2.6 | 1.90±2.6 | 0.62 |
| Maximum pain 24 hrs | 2.51±3.0 | 2.83±3.1 | 2.21±2.9 | 0.34 |
| Current gout flare severity: Baseline | 0.41 | |||
| Mild | 14 (47%) | 9 (50%) | 5 (42%) | |
| Moderate | 10 (33%) | 7 (39%) | 3 (25%) | |
| Severe | 5 (17%) | 2 (11%) | 3 (25%) | |
| Very Severe | 1 (3%) | 0 (0%) | 1 (8%) | |
| SATMED4 subscale and total scores | ||||
| Undesirable side effects | 14.0±26.0 | 18.6±29.7 | 9.6±21.3 | 0.18 |
| Treatment effectiveness | 60.6±32.9 | 54.8±34.6 | 66.1±30.7 | 0.17 |
| Convenience of use | 76.2±25.1 | 74.7±25.3 | 77.6±25.1 | 0.65 |
| Impact on daily activities | 65.3±32.3 | 57.0±35.1 | 73.0±27.7 | 0.05 |
| Medical care | 69.9±30.4 | 66.3±32.0 | 73.3±28.8 | 0.36 |
| Global satisfaction | 68.8±30.7 | 63.9±33.5 | 73.4±27.5 | 0.22 |
| Total score | 57.9±18.2 | 55.1±19.0 | 60.5±17.3 | 0.25 |
Other race includes: Native Hawaiian or other pacific islander, American Indian or Alaskan native, Asian, Other and mixed
Missing frequency, n=3
Validated gout flare was defined as the presence of 3 (ore more) of the 4 following criteria: Pt. reported gout flare, warm joint, swollen joint, average pain >=3 in the last 24 hrs
MD-reported confirmation of gout diagnosis was done for all 84 subjects
Patient satisfaction with ULT was assessed by validated Treatment Satisfaction with Medications questionnaire (SATMED) at baseline only. It has 17-items, each scored from 0 to 4. SATMED has six dimensions/sub-scales. A total raw score ranges from 0 to 68, with higher score indicating more satisfaction with treatment. Both dimension and total scores are transformed 0–100.
Bold indicates a significant p-value <0.05
Finalization of Key Study Procedures/Tools
GoutWell and 2-weekly gout flare assessments
We modified VioScreen™, an online highly reliable Food Frequency Questionnaire (FFQ) tool,[14] a self-reported assessment of food choices and portion sizes over the past 30 days, in to GoutWell to be gout-specific (inclusion of additional food items such as anchovies etc.) and used with modifications in our study (details below). It measured the 20 variables below (appendix 1): calories, carbohydrates, protein, fat, total saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), calcium, caffeine, alcohol consumption, cooked lean meat (beef, pork etc.), cooked lean meat (sausage, luncheon meats), cooked lean meat from organ meats, cooked lean meat (chicken, turkey, poultry), and total fat.
GoutWell provided participants with intervention-specific personalized message regarding diet or cherry extract adherence to increase the chance of success of each intervention. GoutWell also sent an automated personalized email reminder to all enrolled patients regularly every 2-weeks asking them if they have had a gout flare in the last 2-weeks.
After the study participant completed the baseline FFQ, a summary report was created from GoutWell, and the patient entered the Interactive Behavioral Feedback module of the system to guide them to develop a customized dietary plan (appendix 2). This report highlighted the amount and % excess/ deficient intake of various diet components, and by its cross-linking to risk imparted by these factors and an individual’s decision for the diet-related changes he/she was willing to make at a given time, a registered dietitian (A.W., or B.D.) generated an individualized and personalized diet modification plan. The plan included suggestions and assistance such as controlling food cues, priming the food environment to make beneficial food selections, increasing knowledge of positive gout-related diet changes to promote initial dietary changes; and tips on portion control of gout-related foods, advance food purchase planning, and consistency in healthy food selection for longer-term dietary adherence. The information related to diet modification recommendations was presented in easy graphics via email to enhance patient understanding [24] and enhanced during calls with dietitian.
GoutWell-assisted 2-weekly gout flare assessment was sent via an email link to each study participant. High initial completion rates were noted in the first 7 surveys (>80%), with some waning of response rate by the 12th assessment (>75%) and further decline by the 18th survey (62%; Appendix 3).
Confirmation of gout diagnosis by patient’s healthcare provider and patient self-report of gout classification criteria
The diagnosis of gout was confirmed in 90% (84/93) of the participants who self-reported gout, most (>90%) within 2-weeks of the first contact with the healthcare provider’s office. Diagnosis was not gout for two potential participants (2%; 2/93) and we were unable to get a response from healthcare provider office regarding the diagnosis for seven potential participants (8%; 7/93).
We obtained patient self-reported gout classification criteria from all participants (100%; 84/84) and 92% (77/84) participants met the 1977 ACR classification criteria for gout, but reporting rates were for healthcare provider-reported gout classification criteria: 80% provided data (67/84) and 67% (45/67) met gout classification criteria (Appendix 4). The overall patient-provider concordance for satisfying the 1977 ACR classification criteria for gout was 67% (45/67) with overlap of > 70% for seven gout classification criteria (Appendix 5). Mean (SD) gout classification criteria were higher for self-reported vs. healthcare provider-reported 8.6±3.1 vs. 4.8±2.6 (Appendix 4).
Centralized laboratory-assisted serum urate (SU) testing
The study coordinator identified the nearest Quest® laboratory site and requested all study participants to get a blood draw for baseline SU, scheduled based on their preference. A copy of the laboratory slip and confirmation slip was sent to each study participant via email to give to the laboratory personnel on arrival to the Quest® facility. Participants were reminded of the appointment via email and phone call 1 day before the blood draw. The blood draw was rescheduled for those who missed it. Test results were sent to the study team in a HIPAA-compliant manner over a secure server/fax and were recorded in the study database by a trained coordinator. Participants were provided additional incentive ($40 incentive per draw) for completing the baseline and 9-month SU blood draws to account for the inconvenience. Completion rates for baseline and 9-month SU blood draw were 100% and 77%, respectively.
Satisfaction with intervention and study website, Study feasibility and acceptability
Participant satisfaction with the intervention was high (0–100 scale) with intervention being easy, enjoyable, understandable, and helpful (Table 2). The overall satisfaction with intervention was moderate-high. No significant differences by treatment arm were noted except that cherry extract intake was more understandable than the diet modification intervention (p=0.01; Table 2).
Table 2.
Satisfaction with the intervention and of intervention components/goals and acceptability of the study assessed at 9-month end of study visit
| Cherry extract (N = 41) Mean ± SD | Diet Modification (N = 43) Mean ± SD | p-value, parametric test | |
|---|---|---|---|
| Feasibility of and satisfaction with the study intervention, 0–100 (higher=better) | |||
| Ease of doing the intervention | 83.5 (23.5) | 75.7 (22.6) | 0.14 |
| Intervention was understandable | 88.2 (18.4) | 74.3 (27.6) | 0.01 |
| Enjoyed the intervention | 72.6 (27.0) | 65.3 (28.7) | 0.70 |
| Intervention was helpful | 73.0 (25.9) | 69.8 (28.2) | 0.60 |
| Overall satisfaction with the intervention | 76.6 (23.8) | 70.9 (28.1) | 0.33 |
| Satisfied (Very or extremely satisfied) with intervention components/goals | |||
| Nutritional goal of 25% reduction in seafood | N/A | 16 (44%) | |
| Nutritional goal of 10% reduction in meat intake | N/A | 17 (47%) | |
| Nutrition goal of 10% increase in skim milk intake | N/A | 11 (31%) | |
| Take cherry extract with breakfast | 29 (73%) | N/A | |
| Keep cherry bottle next to the coffee maker | 15 (38%) | N/A | |
| Add daily reminder on cell phone for cherry | 15 (38%) | N/A | |
| Study Acceptability, 0–100 (higher=better) | |||
| Amount of time for study was acceptable | 87.2 (19.8) | 80.2 (18.5) | 0.11 |
| n (%) | n (%) |
N/A, not applicable; SD, standard deviation
Bold indicates a significant p-value <0.05
Subject satisfaction was high for the overall study participants with >70% people moderately to extremely satisfied with various aspects of study website (Table 3). Participants reported high rate of concordance of website content with the personalized plan (Table 3). Satisfaction ratings were similar across the two active comparator arms.
Table 3.
Web-based material consumer rating form at 3 month follow-up to assess patient satisfaction with the web based study material and the study intervention
| Combined (n=84) | Cherry (n=43) | Diet (n=41) | ||||||
|---|---|---|---|---|---|---|---|---|
| Question | Not at all | Slightly | Moderately | Very much so | Extremely | # Positive Responses | # Positive Responses | p-value |
| Website Interaction | ||||||||
| 1. How easy was it to use the website overall? | 7% | 0% | 21% | 31% | 42% | 95% | 92% | 0.54 |
| 2. How easy was it to use the website tabs? | 8% | 1% | 18% | 31% | 42% | 91% | 92% | 0.83 |
| 3. How pleasant or visually appealing was the website? | 9% | 3% | 29% | 29% | 31% | 90% | 86% | 0.57 |
| 4. To what extent did the icons or ‘tabs’ appear readable? | 8% | 1% | 25% | 31% | 35% | 90% | 92% | 0.83 |
| 5. How easy was it to follow the instructions for logging onto the website? | 8% | 1% | 18% | 37% | 37% | 90% | 92% | 0.83 |
| Website Content | ||||||||
| 6. To what extent did the website content maintain your interest in the website? | 13% | 1% | 35% | 35% | 16% | 82% | 89% | 0.46 |
| 8. Did it seem like the content related to your experience with trying to modify your diet /self-manage cherry extract supplementation was depicted in the website? | 17% | 8% | 33% | 27% | 16% | 73% | 78% | 0.64 |
| 9. To what extend did the setting or place distract you from attending to the website? | 47% | 6% | 27% | 12% | 8% | 42% | 53% | 0.32 |
| 10. To what extent did the written content for the health materials appear readable? | 12% | 1% | 29% | 38% | 21% | 86% | 89% | 0.64 |
| 11. To what extent do you think this information would help you in managing your diet/cherry capsule intake? | 16% | 1% | 34% | 33% | 17% | 83% | 83% | 0.96 |
| Website Self-monitoring Function | ||||||||
| 12. How easy was it to use the self-monitoring function for daily food intake? | 17% | 3% | 39% | 22% | 19% | 78% | 83% | 0.56 |
| 13. How easy was it to use the self-monitoring function for daily cherry extract intake? | 17% | 1% | 31% | 27% | 24% | 83% | 81% | 0.79 |
| Website content concordant with personalized plan | ||||||||
| 7. Did it seem like the content related to your experience with trying to modify your diet/self-manage cherry extract supplementation were depicted in the personalized plan? | 18% | 5% | 34% | 29% | 14% | 76% | 78% | 0.83 |
Answer choices: Not at All, Slightly, Moderately, Very much so, Extremely
Positive response implies that the respondent chose Moderately, Very much so, or Extremely
The amount of time spent for study was acceptable, with non-significantly higher score in cherry extract vs. diet modification group (Table 2).
Dietary Changes
There were no differences in baseline diet quality in cherry extract vs. diet modification groups (Table 4). No between group differences in dietary component intake were seen in cherry extract vs. diet modification groups from baseline to follow-up visits, except a significantly lower total calories and total carbohydrate intake at 6-months in the diet modification vs. cherry extract group (p<0.05), and borderline significantly lower total fat intake (p=0.05; Table 5), respectively. Some increase in all three diet components occurred from 6- to 9-months in the diet modification group, values were still lower than those at the baseline (Table 5). There was no meaningful BMI change in either group (Table 5).
Table 4.
Baseline dietary component for all participants and comparison between cherry extract vs. diet modification arms
| Variable name | All participants with MD confirmed gout (N= 84) Mean ± SD | Randomized to cherry extract (N = 41*) Mean ± SD | Randomized to diet modification (N=43*) Mean ± SD | p-value |
|---|---|---|---|---|
| Body Mass Index, kg/m2 | 32.7±8.5 | 32.5±7.9 | 34.0±10.0 | 0.49 |
| Total Calories, Kcal | 2099.4±728.7 | 2015.0±952.9 | 2012.5±954.7 | 0.99 |
| % calories from carbohydrate intake | 44%±10% | 43% ±10% | 46% ±11% | 0.15 |
| % calories from fat intake | 38%±9% | 38% ±10% | 37%±8% | 0.48 |
| % calories from protein intake | 16%±4% | 16% ±4% | 15% ±4% | 0.34 |
| Protein, grams | 80.62±30.7 | 78.2±35.3 | 75.7±35.6 | 0.75 |
| Carbohydrate, grams | 226.70±85.2 | 218.4±123.5 | 225.9±122.4 | 0.78 |
| Fat, grams | 88.42±38.6 | 83.8±42.9 | 83.3±42.5 | 0.95 |
| Total Saturated Fatty Acids (SFA), grams | 28.1±13.5 | 26.4±15.4 | 26.7±14.7 | 0.95 |
| Monounsaturated Fatty Acids (MUFA), grams | 32.3±14.8 | 19.6±12.0 | 19.8±10.5 | 0.79 |
| Polyunsaturated Fatty Acids (PUFA), grams | 21±10.8 | 31.1±14.6 | 30.1±17.1 | 0.94 |
| Fiber, grams | 21.1±9.6 | 19.9±10.3 | 20.1±9.1 | 0.94 |
| Calcium, mg | 957.3 ±456.5 | 885.0±473.7 | 915.8±508.7 | 0.78 |
| Alcohol, oz | 1.2 ±1.65 | 1.1 ± 1.6 | 1.0 ±1.7 | 0.73 |
| Caffeine, mg | 201.8 ±163.5 | 223.1±194.3 | 179.8±140.4 | 0.24 |
| Cooked lean meat beef, pork, veal, lamb, and game, oz | 1.35 ±1.51 | 1.6±1.6 | 1.1±1.5 | 0.12 |
| Cooked Lean Meat, frank, sausage, luncheon meats, oz | 0.6 ±0.6 | 0.6±0.6 | 0.6±0.7 | 0.88 |
| Cooked lean meat from organ meats, oz | 0.014±0.06 | 0.01±0.05 | 0.01±0.06 | 0.72 |
| Cooked lean meat chicken, turkey, and other poultry, oz | 1.48 ±1.2 | 1.3±1.0 | 1.6±1.3 | 0.25 |
| Healthy Eating Index (HEI) 2010 score | 64.3 ±10.0 | 64.6±11.8 | 62.7±10.7 | 0.42 |
SD, standard deviation
HEI2010: The Healthy Eating Index (HEI) is a measure of diet quality used to assess how well a set of foods aligns with key recommendations of the dietary guidelines for Americans. The HEI uses a scoring system to evaluate a set of foods. The scores range from 0 to 100.
Table 5.
Dietary component changes by treatment arm: Baseline and study follow-ups every 3-months
| Baseline | 3-Month | 6-Month | 9-Month | Overall p-value over 9-months | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Mean (SD) | p-value | N | Mean (SD) | p-value | N | Mean (SD) | p-value | N | Mean (SD) | p-value | ||
| Body Mass Index, Kg/m2 | 0.49 | 0.66 | 0.22 | 0.16 | 0.33 | ||||||||
| Cherry | 41 | 32.5 (7.9) | 40 | 32.5 (7.3) | 35 | 32.2 (7.9) | 31 | 32.0 (6.5) | |||||
| Diet | 40 | 34.0 (10.0) | 30 | 33.4 (8.7) | 27 | 35.2 (11.1) | 20 | 35.0 (8.8) | |||||
| Total Calories, Kcal | 0.99 | 0.47 | 0.03 | 0.40 | 0.39 | ||||||||
| Cherry | 41 | 2015.0 (952.9) | 40 | 1837.9 (714.4) | 35 | 1707.5 (754.1) | 31 | 1765.5 (813.6) | |||||
| Diet | 43 | 2012.5 (954.7) | 32 | 1697.8 (914.1) | 28 | 1307.1 (682.9) | 23 | 1537.6 (1172.9) | |||||
| % calories from carbohydrate intake | 0.16 | 0.13 | 0.80 | 0.21 | 0.13 | ||||||||
| Cherry | 41 | 43% (10%) | 40 | 43% (8%) | 35 | 45% (8%) | 31 | 42% (8%) | |||||
| Diet | 43 | 46% (11%) | 32 | 47% (9%) | 28 | 45% (10%) | 23 | 45% (13%) | |||||
| % calories from fat intake | 0.48 | 0.64 | 0.57 | 0.61 | 0.45 | ||||||||
| Cherry | 41 | 38% (10%) | 40 | 36% (8%) | 35 | 36% (7%) | 31 | 37% (8%) | |||||
| Diet | 43 | 37% (8%) | 32 | 36% (9%) | 28 | 35% (8%) | 23 | 36% (8%) | |||||
| % calories from protein intake | 0.35 | 0.62 | 0.14 | 0.48 | 0.82 | ||||||||
| Cherry | 41 | 16% (4%) | 40 | 16% (3%) | 35 | 16% (4%) | 31 | 18% (8%) | |||||
| Diet | 43 | 15% (4%) | 32 | 18% (3%) | 28 | 18% (8%) | 23 | 16% (6%) | |||||
| Protein, grams | 0.75 | 0.58 | 0.16 | 0.42 | 0.41 | ||||||||
| Cherry | 41 | 78.2 (35.3) | 40 | 73.6 (29.6) | 35 | 66.3 (28.7) | 31 | 73.3 (30.9) | |||||
| Diet | 43 | 75.7 (35.6) | 32 | 68.8 (43.7) | 28 | 55.5 (31.1) | 23 | 63.7 (54.3) | |||||
| Carbohydrate, grams | 0.78 | 0.78 | 0.02 | 0.69 | 0.60 | ||||||||
| Cherry | 41 | 218.4 (123.5) | 40 | 198.9 (90.4) | 35 | 193.1 (91.9) | 31 | 186.5 (99.5) | |||||
| Diet | 43 | 225.9 (122.4) | 32 | 192.4 (103.2) | 28 | 143.3 (76.9) | 23 | 173.3 (146.8) | |||||
| Fat, grams | 0.95 | 0.38 | 0.05 | 0.25 | 0.33 | ||||||||
| Cherry | 41 | 83.8 (42.9) | 40 | 74.7 (33.6) | 35 | 67.0 (30.1) | 31 | 73.3 (36.7) | |||||
| Diet | 43 | 83.3 (42.5) | 32 | 67.0 (40.9) | 28 | 51.7 (30.8) | 23 | 60.3 (45.7) | |||||
| Total Saturated Fatty Acids (SFA), grams | 0.75 | 0.47 | 0.04 | 0.25 | 0.36 | ||||||||
| Cherry | 41 | 26.4 (15.4) | 40 | 23.3 (12.9) | 35 | 21.1 (11.5) | 31 | 23.2 (12.8) | |||||
| Diet | 43 | 26.7 (14.7) | 32 | 21.1 (12.4 | 28 | 15.4 (9.1) | 23 | 19.1 (12.5) | |||||
| Monounsaturated Fatty Acids (MUFA), grams | 0.79 | 0.26 | 0.06 | 0.21 | 0.25 | ||||||||
| Cherry | 41 | 19.6 (12.0) | 40 | 28.3 (12.2) | 35 | 25.1 (10.8) | 31 | 27.3 (12.7) | |||||
| Diet | 43 | 19.8 (10.5) | 32 | 24.4 (16.4) | 28 | 19.4 (12.8) | 23 | 21.9 (18.1) | |||||
| Polyunsaturated Fatty Acids (PUFA), grams | 0.94 | 0.66 | 0.16 | 0.39 | 0.56 | ||||||||
| Cherry | 31.1 (14.6) | 40 | 16.9 (7.9) | 35 | 15.3 (7.0) | 31 | 16.8 (9.6) | ||||||
| Diet | 41 | 30.1 (17.1) | 32 | 16.0 (10.7) | 28 | 12.5 (8.4) | 23 | 14.2 12.5) | |||||
| Fiber, grams | 0.94 | 0.77 | 0.34 | 0.75 | 0.97 | ||||||||
| Cherry | 41 | 19.9 (10.3) | 40 | 19.0 (8.6) | 35 | 17.8 (8.2) | 31 | 17.1 (7.9) | |||||
| Diet | 43 | 20.1 (9.1) | 32 | 19.6 (10.3) | 28 | 15.8 (8.8) | 23 | 18.1 (14.5) | |||||
| Calcium, mg | 0.78 | 0.88 | 0.07 | 0.29 | 0.63 | ||||||||
| Chery | 41 | 885.0 (473.7) | 40 | 810.2 (394.8) | 35 | 762.1 (385.3) | 31 | 831.9 (462.1) | |||||
| Diet | 43 | 915.8 (508.7) | 32 | 828.2 (583.9) | 28 | 588.6 (349.1) | 23 | 684.4 (551.0) | |||||
| Alcohol, oz | 0.95 | 0.58 | 0.48 | ||||||||||
| Cherry | 41 | 1.1 (1.6) | 40 | 1.1 (1.4) | 35 | 1.0 (1.3) | 31 | 1.0 (1.5) | 0.67 | 0.59 | |||
| Diet | 43 | 1.0 (1.7) | 32 | 1.0 (1.7) | 28 | 0.8 (1.4) | 23 | 0.8 (1.6) | |||||
| Caffeine, mg | 0.73 | 0.28 | 0.65 | 0.78 | 0.59 | ||||||||
| Cherry | 41 | 223.1 (194.3) | 40 | 210.3 (172.5) | 35 | 160.0 (142.4) | 31 | 152.0 (147.4) | |||||
| Diet | 43 | 179.8 (140.4) | 32 | 167.8 (154.8) | 28 | 178.5 (178.7) | 23 | 162.5 (124.7) | |||||
| Cooked Lean Meat, frank, sausage, luncheon meats, oz | 0.12 | 0.75 | 0.75 | 0.82 | 0.95 | ||||||||
| Cherry | 41 | 1.6 (1.6) | 40 | 0.7 (1.0) | 35 | 0.6 (0.5) | 31 | 0.6 (0.8) | |||||
| Diet | 43 | 1.1 (1.5) | 32 | 0.7 (0.7) | 28 | 0.5 (0.5) | 23 | 0.6 (0.7) | |||||
| Cooked lean meat beef, pork, veal, lamb, and game, oz | 0.88 | 0.37 | 0.13 | 0.45 | 0.14 | ||||||||
| Cherry | 41 | 0.6 (0.6) | 40 | 1.3 (1.3) | 28 | 1.0 (1.0) | 31 | 1.3 (1.5) | |||||
| Diet | 43 | 0.6 (0.7) | 32 | 1.0 (1.2) | 18 | 0.7 (0.8) | 23 | 1.0 (1.4) | |||||
| Cooked lean meat from organ meats, oz | 43 | 0.72 | 0.13 | 1.0 | 0.25 | 0.90 | |||||||
| Cherry | 0.01 (0.05) | 40 | 0.02 (0.1) | 35 | 0 (0) | 31 | 0.002 (0.01) | ||||||
| Diet | 41 | 0.01 (0.06) | 32 | 0.002 (0.01) | 28 | 0 (0) | 23 | 0.02 (0.04) | |||||
| Cooked lean meat chicken, turkey, and other poultry, oz | 43 | 0.25 | 0.12 | 0.59 | 0.74 | 0.74 | |||||||
| Cherry | 41 | 1.3 (1.0) | 40 | 1.5 (1.3) | 35 | 1.3 (1.0) | 31 | 1.2 (0.8) | |||||
| Diet | 43 | 1.6 (1.3) | 32 | 1.0 (1.0) | 28 | 1.2 (1.0) | 23 | 1.1 (1.2) | |||||
| HEI2010Score | 0.42 | 0.58 | 0.25 | 0.50 | 0.99 | ||||||||
| Cherry | 41 | 64.6 (11.8) | 40 | 65.5 (11.6) | 35 | 64.4 (11.9) | 31 | 64.8 (10.7) | |||||
| Diet | 43 | 62.7 (10.7) | 32 | 67.1 (11.2) | 28 | 67.7 (10.2) | 23 | 62.6 (12.2) | |||||
Bold indicates a significant p-value <0.05
Exploratory Outcomes: HAQ section scores, current pain, well-being and proportion with target SU
Baseline HAQ domain scores were similar for cherry extract and diet modification arms (Table 6). Comparing 9-month to baseline scores, six of the eight HAQ domains improved significantly from baseline to 9-months in cherry extract vs. two HAQ domains in the diet modification group (Table 6).
Table 6.
Baseline and 9-month HAQ domain scores for participants with both values available
| All participants (N= 58) Mean ± SD | Cherry extract (N = 32*) Mean ± SD | Diet modification (N=26*) Mean ± SD | Cherry vs. diet p-value | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | 9-month FU | Baseline | 9-month FU | p-value | Baseline | 9-month FU | p-value | Baseline | 9-month | |
| HAQ-DI domains | ||||||||||
| Dressing | 0.41±0.8 | 0.20±0.5 | 0.44±0.8 | 0.22±0.8 | 0.05 | 0.38±0.8 | 0.15±0.5 | 0.13 | 0.97 | 0.37 |
| Arising | 0.50±0.7 | 0.22±0.5 | 0.53±0.8 | 0.28±0.8 | 0.04 | 0.46±0.6 | 0.15±0.4 | 0.03 | 0.11 | 0.02 |
| Eating | 0.17±0.5 | 0.10±0.4 | 0.22±0.5 | 0.16±0.5 | 0.16 | 0.12±0.4 | 0.04±0.2 | 0.42 | 0.51 | <0.001 |
| Walking | 0.78±0.9 | 0.34±0.7 | 0.84±1.0 | 0.38±0.8 | 0.009 | 0.69±0.8 | 0.31±0.7 | 0.048 | 0.33 | 0.61 |
| Hygiene | 0.67±1.0 | 0.26±0.7 | 0.66±0.9 | 0.31±0.9 | 0.006 | 0.69±1.0 | 0.19±0.6 | 0.009 | 0.42 | 0.29 |
| Reaching | 0.50±0.8 | 0.29±0.6 | 0.56±0.8 | 0.31±0.6 | 0.03 | 0.42±0.8 | 0.27±0.6 | 0.32 | 0.73 | 0.74 |
| Gripping | 0.33±0.7 | 0.17±0.5 | 0.31±0.6 | 0.16±0.5 | 0.06 | 0.35±0.7 | 0.19±0.5 | 0.25 | 0.44 | 0.82 |
| Outside activity | 0.79±1.0 | 0.47±0.9 | 0.84±1.0 | 0.44±0.9 | 0.003 | 0.73±1.0 | 0.50±0.9 | 0.30 | 0.77 | 0.76 |
| HAQ-DI score (mean ± SD) | 0.52±0.6 | 0.26±0.7 | 0.55±0.7 | 0.28±0.5 | 0.001 | 0.48±0.6 | 0.23±0.4 | 0.047 | 0.61 | 0.13 |
9-month, cherry vs. diet modification
HAQ; Health assessment questionnaire; HAQ, higher scores are worse and indicate more disability
Bold indicates a significant p-value <0.05
There were no significant differences in pain intensity (current, last 24 hours), well-being or target SU < 5 mg/dl or < 6 mg/dl, between groups over study follow-up (Table 7). Small with-in group improvements were noted in current pain intensity or well-being from baseline to follow-up (Table 7).
Table 7.
Exploratory Outcomes
| Baseline | 3-Month | 6-Month | 9-Month | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Mean (SD) | p-value | N | Mean (SD) | p-value | N | Mean (SD) | p-value | N | Mean (SD) | p-value | |
| Current Pain Intensity, 0–10 | ||||||||||||
| Cherry extract | 41 | 2.17 (2.82) | 0.40 | 41 | 1.27 (2.37) | 0.87 | 37 | 1.22 (2.17) | 0.67 | 32 | 1.03 (1.93) | 0.71 |
| Diet modification | 43 | 1.65 (2.52) | 37 | 1.35 (1.98) | 31 | 1.00 (1.98) | 26 | 0.85 (1.80) | ||||
| Average Pain in last 24 hrs, 0–10 | ||||||||||||
| Cherry extract | 41 | 2.19 (2.60) | 0.62 | 41 | 1.27 (2.31) | 0.69 | 37 | 1.11 (2.09) | 0.72 | 32 | 0.84 (1.44) | 0.99 |
| Diet modification | 43 | 1.91 (2.64) | 37 | 1.08 (1.79) | 31 | 0.94 (1.78) | 26 | 0.85 (1.69) | ||||
| Well-being (0–10; lower=better) | ||||||||||||
| Cherry extract | 41 | 3.10 (2.83) | 0.89 | 41 | 1.85 (2.57) | 0.40 | 37 | 1.86 (2.45) | 0.64 | 32 | 1.91 (2.51) | 0.50 |
| Diet modification | 43 | 2.70 (2.40) | 37 | 2.35 (2.67) | 31 | 1.61 (1.84) | 26 | 1.46 (2.44) | ||||
| % with sUA < 6 mg/dl | ||||||||||||
| Cherry extract | 41 | 11 (26.8%) | 0.43 | N/A | N/A | 34 | 7 (20.6%) | 0.62 | ||||
| Diet modification | 43 | 15 (34.9%) | N/A | N/A | 31 | 8 (25.8%) | ||||||
| % with sUA < 5 mg/dl | ||||||||||||
| Cherry extract | 41 | 6 (14.6%) | 0.84 | N/A | N/A | 34 | 2 (5.9%) | 0.18 | ||||
| Diet modification | 43 | 7 (16.3%) | N/A | N/A | 31 | 5 (16.1%) | ||||||
N/A, not applicable, since sUA were assessed at baseline and at 9-months only
Study End Qualitative De-Briefing
Qualitative debriefing of study participants at study exit revealed the following main messages: (1) overall study enjoyment; (2) future study improvements; (3) the preference for little more human vs. internet interaction; (4) the hassle of study assessment reminders; (5) gout flare surveys were too frequent; (6) suggestion to have larger number of people participate in each diet and cherry phone session; and (7) time commitment to the study (Appendix 6). Overall, patients reported a positive study experience, and constructive feedback regarding the frequency of assessments and the reminders and their preference to use a laboratory at their healthcare provider rather than the Quest® lab (more convenient).
Discussion
This report of patient-centered outcomes and key study procedure finalization adds to our previous report of primary and secondary study outcomes from our pilot Internet gout RCT, mini-GOUCH [12]. A CONSORT checklist provides the key details of the randomized trial (Appendix 7). Study limitations included open-label design, no placebo arm, possible regression to the mean, limited generalizability to non-Internet gout cohorts, and loss to follow-up. A low proportion of patients in our Internet study (37%) were currently on ULT, consistent with poor adherence with ULT in gout [25–27], and possibly may be due to selection bias among people being recruited in the study, who might be less interested in pharmacological therapies and more interested in alternative therapies. Poor adherence to gout therapy and suboptimal gout outcomes [25–27] have led to testing of a nurse-led management program [28], which dramatically improved allopurinol adherence and gout outcomes, and motivated us to search for complimentary therapies for gout. Several findings deserve further discussion.
We found that the Internet study procedures including the study interventions were feasible and acceptable to study participants, who were also satisfied with the Internet website content, function and interaction. This indicated that an Internet study design is acceptable and feasible to conduct of trials of dietary supplements and dietary modification in gout. Qualitative de-briefing of study participants at study exit revealed overall high satisfaction with study procedures by participants and provided important insights and improvements for the next step hypothesis-testing trial. These included re-designing study assessment reminders and gout flare surveys, more human interaction (instituting a baseline and three monthly coordinator phone calls), having larger numbers of participants in each diet and cherry phone session and clarifying time commitments for the study participation.
We noted a reduction in the intake of total calories and carbohydrates in both groups, and a greater reduction in the diet modification group at 6-months (non-significant at 9-months). Notably, our 0-, 3 and 6-month dietitian telephone sessions with participants were designed to motivate participants and potentially address this well-described phenomenon of short-term efficacy of dietary changes in observational or randomized trials [29]. However, the reduction in effect size noted between 6 and 9 months indicated that some loss of response was evident. This has implications for the future trials of diet modification in gout. More frequent diet sessions, larger groups for the calls with an opportunity to for more interaction, a different timing of diet sessions, or a more frequent contact by the study coordinator via phone and/or email, or inclusion of more behavioral components to keep participant involved might help increase the durability of the effect of diet modification intervention. Some improvements in the cherry extract group might be attributable to diet changes that patients made. Inclusion of a placebo arm and instructions to patients not to change their diet in the future placebo-controlled RCT of cherry extract will help reduce or eliminate the effect related to dietary changes.
We also finalized key study procedures including the modification of VioScreen™ an online dietary assessment tool, into a gout-specific FFQ, GoutWell, gout flare surveys, gout diagnosis confirmation by participant’s healthcare provider, collection of patient-reported gout classification criteria and the SU collection by a centralized national laboratory. Goutwell also sent gout flare assessments and reminders. Prospective collection of validated gout flares [30, 31] has been challenging in previous trials in patients with gout. In the current pilot study, we demonstrated successful prospective gout flare assessment, i.e., 82% in cherry extract and 69% in the diet modification groups completed these assessments overall with higher completion rates in the beginning compared to the end of the study. We performed 18 such assessments per participant, and based on constructive feedback in qualitative debriefing, we will modify the frequency of these assessments and modify use of technological solutions to improve response rates.
Physician confirmation of presence/absence of gout diagnosis was achieved in 92% of interested participants, indicating that this approach is practical for our future trial. Success in obtaining data on gout classification criteria from patients (100%) was higher than that from the healthcare provider offices (80%). More people met the classification criteria for gout in patient-reported (92%) vs. provider-reported criteria (67%). This could indicate either higher inaccuracy vs. better recall by patients vs. providers, and their relative contributions can not be determined with the current data. Physician-assessed classification criteria is usually the gold standard in typical pharmaceutical trials, but this study suggests that patient-reported criteria may be a practical alternative, since most criteria represent patient experience and are obtained with history rather than physical examination. We considered using the 2015 ACR gout classification but decided in favor of the 1977 gout classification criteria due to their simplicity. The details needed to document the 2015 ACR gout classification (time course and bursa involvement), and the use of new technology ( ultrasound and dual-energy CT), made this inappropriate for our study, since we were seeking historical documentation of these criteria as per the patient or healthcare provider report. A reasonably high rate of SU blood draw completion was noted at baseline (100%) and 9-month (77%) SU blood draw, indicating that this is a practical approach when additional study incentive is provided due to long driving distance and the inconvenience.
Our study provides data on exploratory outcomes including HAQ sections, current pain, well-being and dietary changes. Six of the eight HAQ sections improved notably in the cherry extract group vs. two HAQ sections in the diet modification group. This finding, in conjunction with our previous finding of improvement in overall HAQ score and gout flares with cherry extract [12], provides further insight into the mechanism of improvement of HAQ scores with cherry extract use. HAQ is an OMERACT-endorsed valid measure of function for clinical trials in gout [21]. This study provides insights into changes in HAQ section scores. We previously reported that the total mean HAQ scores significantly improved from baseline to 9-months, to 0.28 vs. 0.55 in cherry extract (p=0.001), but not in the diet modification group, 0.23 vs. 0.48 (p=0.06) [12]. Small, insignificant differences in pain intensity (current and last 24 hours) and well-being between treatment arms is consistent with observations for maximum pain intensity in our previous report [12].
In summary, this report of patient-centered outcomes including study/intervention feasibility and acceptability and finalization and implementation of key study procedures provides further evidence the Internet gout trials are possible for studies of complementary and alternative treatment strategies. Given the evidence of potential improvement of gout flares and HAQ scores in the cherry extract arm in our previous report [12], an adequately-powered hypothesis-testing trial of cherry extract vs. placebo is needed to assess whether cherry extract is efficacious in gout and to understand the underlying mechanisms. Borderline improvements in mean HAQ scores and gout flares in diet modification [12], and a strong patient preference for studies of diet as the top research agenda [9], indicates that a future assessment of diet modification vs. usual care, or intensification of diet modification with behavioral intervention vs. usual care may also be needed. Such studies can help us understand the role of diet and dietary supplements in the management of gout, and fill knowledge gaps highlighted by gout treatment guidelines [10].
Supplementary Material
Acknowledgements:
We thank all the patients for participating in the study.
Funding:
This study was funded by an intramural grant from the UAB Center for Outcomes and Effectiveness Research and Education (COERE)/ Minority Health Research Center (PI, Singh) and an intramural grant from the UAB Center for Clinical and Translational Studies (CCTS; PI, Singh). The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.
List of Abbreviations
- CONSORT
CONsolidated Standards of Reporting Trials
- IRB
Institutional Review Board
- UAB
University of Alabama at Birmingham
- RCT
randomized controlled trial
- HAQ
Health assessment questionnaire
- AEs
adverse events
- SU
serum urate
- ACR
American College of Rheumatology
Footnotes
Declarations
Ethics approval and consent to participate: The University of Alabama at Birmingham’s (UAB) Institutional Review Board (IRB) approved this study. Each patient participating in the study provided informed consent. All investigations were conducted in conformity with ethical principles of research.
Conflict to publish: Not applicable
Availability of data and materials: We will make data available to colleagues, after appropriate approvals and permissions from the respective IRBs including the UAB IRB have been obtained, and UAB data security and data transfer requirements are met.
Financial Conflict: JAS has received consultant fees from Crealta/Horizon, Fidia, UBM LLC, Medscape, WebMD, the National Institutes of Health and the American College of Rheumatology. JAS is a member of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS served as a member of the American College of Rheumatology’s (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. JAS is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. SM has no relevant disclosures. RW is the owner and CEO of Viocare, a company that markets online dietary assessment tools. KGS has received research grants from Amgen, Ironwood/AstraZeneca, Horizon, Merck, SOBI, and Takeda pharmaceuticals and consultant fees from Abbott, Amgen, Ironwood/AstraZeneca, Bayer, BMS, Horizon, Lilly, Merck, Pfizer, Radius, Roche/Genentech, SOBI, and Takeda pharmaceuticals. Other authors have no relevant disclosures.
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