Individualized decision aid for diverse women with lupus nephritis (IDEA-WON): A randomized controlled trial.

BACKGROUND: Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis. METHODS AND FINDINGS: In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence. CONCLUSIONS: An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02319525.

Development and content validity of the Lupus Foundation of America rapid evaluation of activity in lupus (LFA-REAL™): a patient-reported outcome measure for lupus disease activity.

BACKGROUND/PURPOSE: The LFA REAL™ is a measurement system for evaluating lupus disease activity from both clinician and patient perspectives. Patients' viewpoints are captured using a patient-reported outcome (PRO) questionnaire. A series of visual analog scales are designed to rate disease severity and progress over the past 4 weeks. Brief instructions guide the patient to distinguish between active, potentially reversible symptoms and chronic pain or discomfort that are more likely due to damage. Beyond its simplicity and efficiency, the PRO can provide versatile assessments from a global, organ-based, and symptom-specific level. This paper describes the patient-centered approach used to evaluate the content validity of the LFA-REAL PRO. METHODS: The PRO was developed in accordance with FDA guidance. A two-phase qualitative study was performed with 25 lupus patients, 10 who participated in concept elicitation (Phase 1) and 15 in cognitive debriefing interviews (Phase 2). Qualitative data were analyzed using ATLAS.ti software v7.5. Upon completion of the interviews, participants completed the draft PRO and additional measures to characterize the sample. RESULTS: The mean age of participants was 45.6 and 88% were female, as expected in a lupus population. The mean SF-36 physical component score was 29.8 and the mean mental component score was 46.4. Phase 1 elicited symptom saturation and mapping of the draft PRO. Fatigue was reported by 100% of patients, highlighting its importance as a measurable domain. Additionally, 100% of patients spontaneously mentioned arthritis, which may be more important to this group than previously estimated, substantiating the approach of this PRO to break down components of arthritis into joint pain, stiffness, and swelling. Shortness of breath and fever were reported more frequently than expected. Phase 2 data demonstrated that participants found the instrument easy to use and offered recommendations to improve clarity, leading to adjustments in wording and formatting. CONCLUSIONS: Results suggest that the LFA-REAL PRO has content validity and, with some modifications suggested by participants, is ready for quantitative validation, including tests of reliability, validity, responsiveness to change, and performance relative to other PROs used in lupus trials. After validation, the LFA-REAL system is intended for use in clinical practice and research.

The ALPHA Project: Establishing consensus and prioritisation of global community recommendations to address major challenges in lupus diagnosis, care, treatment and research.

The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus effort to identify, prioritise and address top barriers in lupus impacting diagnosis, care, treatment and research. To conduct this process, the ALPHA Project convened a multistakeholder Global Advisory Committee (GAC) of lupus experts and collected input from global audiences, including patients. In phase I, the ALPHA Project used expert interviews and a global survey of lupus experts to identify and categorise barriers into three overarching pillars: drug development, clinical care and access to care. In phase II, reported here, the GAC developed recommended actionable solutions to address these previously identified barriers through an in-person stakeholder meeting, followed by a two-round scoring process. Recommendations were assessed for feasibility, impact and timeline for implementation (FIT), where potential FIT component values were between 1 and 3 and total scores were between 3 and 9. Higher scores represented higher achievability based on the composite of the three criteria. Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.

Establishing Consensus Understanding of the Barriers to Drug Development in Lupus.

OBJECTIVE: Due to the extreme heterogeneity of lupus and the lack of consensus among stakeholders, pharmaceutical and biotechnology companies have had limited success in developing treatments for lupus. For this reason, the Lupus Foundation of America (LFA), researchers at the Center for the Study of Drug Development at Tufts University School of Medicine (Tufts CSDD) and an advisory committee of 13 international lupus experts collaborated to launch the Addressing Lupus Pillars for Health Advancement (ALPHA) project. METHODS: To inform the ALPHA project, 17 in-depth interviews among lupus experts and a global survey among lupus drug development and clinical care professionals was conducted to identify, characterize, and prioritize fundamental barriers and validate findings. RESULTS: The global survey received 127 responses from experts across 20 countries. Results of the in-depth interviews and the survey findings were consistent. Top barriers to developing new medical treatments for lupus included the lack of a clear definition of the disease with respondents identifying 30 autoimmune conditions that may be lupus-related; lack of predictive biomarkers; flaws in clinical trial designs; and a lack of reliable outcome measures. CONCLUSION: The study findings encourage drug development professionals to validate disease-specific measures and to identify if specific symptoms are caused by lupus. This original research also provides a methodology that can be applied to highly heterogenous diseases where low consensus on diagnosis and treatment exists among drug development and health professionals.

The Spectrum of Health Domains Important to Lupus Patients Early Development of a Disease Activity Patient Reported Outcome.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) face lifelong challenges from chronic and disabling symptoms. The toolkit for assessing patient progress lacks a simple, scalable index that includes both physician assessments and patient experiences. Clinician and patient reported outcomes (ClinROs and PROs) were developed in isolation and discrepancies in their results promote confusion. The Lupus Foundation of America-Rapid Evaluation of Activity in Lupus (LFA-REAL™) was designed as a simple, versatile instrument of simple additive scales. Dual physician and patient components allow for a complete evaluation of disease activity. This report presents the early development of the LFA-REAL™ PRO. METHODS: An initial focus group was conducted consisting of 10 SLE patients who ranked 32 areas of health and identified additional domains that are important to people with lupus. Subsequently, 19 domains were ranked by 100 consecutive patients with SLE from New York and Oklahoma City. RESULTS: The 10 focus group participants were female and had a mean age of 38.6. The dimensions they identified were generally in two categories: symptoms and impacts. The main symptoms were fatigue, joint and muscle pain, and general pain. The main impacts were sleep, drug side effects, and physical well-being. The 100 patients with SLE (90% female, mean age 37.5 years) ranked the 19 fields of health in order of importance. The top eight domains ranked were joint and muscle pain, fatigue, experience of quality of life, general pain, physical well-being, emotional well-being, organ involvement, and family life. Clinicians reviewed the data and decided on an instrument that would differentiate between lupus related symptoms and impact on quality of life as well as differentiate active symptoms from chronic damage. The disease activity instrument draft included all the identified symptoms: rash, joint symptoms (pains, stiffness, and swelling), muscle pain, fatigue, organ involvement symptoms (fever, chest pain, shortness of breath, leg swelling, and other), and hair loss. DISCUSSION: The PRO derived here is a composite disease activity instrument to accompany the physician reported assessment. The ClinRO and the PRO will provide the spectrum of lupus disease activity and bring the patient's experience and provide essential quantitative data to the evaluation of lupus in routine clinical care and clinical research.

Comparison of the Lupus Foundation of America-Rapid Evaluation of Activity in Lupus to More Complex Disease Activity Instruments As Evaluated by Clinical Investigators or Real-World Clinicians.

OBJECTIVE: Lupus disease measures such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index are challenging to interpret. The Lupus Foundation of America-Rapid Evaluation of Activity in Lupus (LFA-REAL) is intended to provide an efficient application of anchored visual analog scores, each representing the individual severity of active symptoms, with the sum of individual scores deriving an overall disease activity assessment. Our objective was to compare the performance of LFA-REAL to systemic lupus erythematosus disease activity assessments and compare scores between trained lupus clinical investigators and clinicians. METHODS: Investigators scored the SLEDAI, BILAG, physician's global assessment (PGA), and LFA-REAL, while the clinicians scored the LFA-REAL. The level of agreement between physicians and instruments was determined. RESULTS: The study included 99 patients (93% women, 31% white, mean ± SD ages 43.4 ± 13.2 years). At the first visit, the mean ± SD SLEDAI score was 5.5 ± 4.5, BILAG score 6.7 ± 7.8, and PGA score 33.6 ± 24.5. The mean ± SD investigator LFA-REAL score was 46.2 ± 42.9, and clinician LFA-REAL score 56.1 ± 53.6. At the second visit, the mean ± SD investigator LFA-REAL score was 41.3 ± 36.7, and clinician LFA-REAL score 48.3 ± 42.6. Total LFA-REAL scores correlated positively with PGA, SLEDAI, and BILAG (ρ = 0.58-0.88, P < 0.001). LFA-REAL scores produced correlation coefficients of ρ > 0.7 for musculoskeletal, mucocutaneous, and renal BILAG domains. The intraclass correlation coefficient between the LFA-REAL scores of investigators and clinicians was 0.79 for visit 1 (P < 0.001) and 0.86 for visit 2 (P < 0.001). CONCLUSION: The LFA-REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians.