Timely access to trial data in the context of a pandemic: the time is now.

OBJECTIVE: Clinical trial data sharing has the potential to accelerate scientific progress, answer new lines of scientific inquiry, support reproducibility and prevent redundancy. Vivli, a non-profit organisation, operates a global platform for sharing of individual participant-level trial data and associated documents. Sharing of these data collected from each trial participant enables combining of these data to drive new scientific insights or assess reproducibility-not possible with the aggregate or summary data tables historically made available. We report on our initial experience including key metrics, lessons learned and how we see our role in the data sharing ecosystem. We also describe how Vivli is addressing the needs of the COVID-19 challenge through a new dedicated portal that provides a direct search function for COVID-19 studies, availability for fast-tracked request review and data sharing. DATA SUMMARY: The Vivli platform was established in 2018 and has partnered with 28 diverse members from industry, academic institutions, government platforms and non-profit foundations. Currently, 5400 trials representing 3.6 million participants are shared on the platform. From July 2018 to September 2020, Vivli received 201 requests. To date, 106 of 201 requests received approval, 5 have been declined, 27 withdrew and 27 are in the revision stage. CONCLUSIONS: The pandemic has only magnified the necessity for data sharing. If most data are shared and in a manner that allows interoperability, then we have hope of moving towards a cohesive scientific understanding more quickly not only for COVID-19 but also for all diseases. Conversely, if only isolated pockets of data are shared then society loses the opportunity to close vital gaps in our understanding of this rapidly evolving epidemic. This current challenge serves to highlight the value of data sharing platforms-critical enablers that help researchers build on prior knowledge.

Immunosuppressant use and hospitalisations in adult patients with systemic lupus erythematosus admitted to a tertiary academic medical centre.

OBJECTIVES: To describe how immunosuppressant use and hospitalisation patterns for SLE have evolved by comparing admission statistics at one academic centre between 2005 and 2013. METHODS: We identified admissions for SLE and for all hospitalised patients by using the hospital electronic database. For adult patients with SLE, a comprehensive chart review was conducted to identify primary indications for hospitalisation, in-hospital mortality, mean length of stay and immunosuppressant use. RESULTS: The number of yearly SLE patient hospitalisations decreased from 178 to 86 between the two times of observation. Infection was the most common reason for hospitalisation accounting for 39.9% of hospitalisations in 2005 versus 31.4% of hospitalisations in 2013 (p=0.29). Lupus flare accounted for 9.6% of admissions in 2005 versus 8.1% of admissions in 2013 (p=0.72). Seven patients died during their hospitalisation (3.9% of admissions) in 2005 as opposed to no inpatient deaths in 2013. Of the 261 admissions between 2010 and 2013, six admissions resulted in death (2.3% of admissions). SLE patient mean length of hospital stay decreased from 7.6 days to 6.4 days (p=0.36) compared with all patient length of stay, which decreased from 6 days to 5.8 days. Corticosteroid use decreased (79.8% to 61.6%, p=0.11) while hydroxychloroquine (27.0% to 59.3%, p<0.001) use increased over time. CONCLUSIONS: The number of hospitalisations, mortality and length of stay among hospitalised patients with SLE decreased over time. Infection was the primary reason for inpatient hospitalisation. Hydroxychloroquine use more than doubled over this same time period with statistical significance. These pilot data suggest improvements in SLE hospitalisation outcomes over time, but larger studies are needed to examine these trends and to understand the relationship between changing medication prescribing patterns and hospitalisation outcomes in patients with SLE.

Impact of standard of care treatments and disease variables on outcomes in systemic lupus erythematosus trials: analysis from the Lupus Foundation of America Collective Data Analysis Initiative.

OBJECTIVE: Most clinical trials for systemic lupus erythematosus (SLE) study the efficacy and safety of investigational agents added to variable background immunosuppressants, which has resulted in high response rates in patients treated with placebo plus standard of care (SOC) plus rescue measures. This project compared the impact of different SOC treatments and disease variables on the outcomes of SLE trials. MATERIAL AND METHODS: Data were obtained from 981 patients receiving only SOC treatments in three nephritis and three general SLE trials to compare response and flare rates on the basis of the British Isles Lupus Assessment Group (BILAG) index, a measure common to all trials. RESULTS: For subjects enrolled in general SLE trials (n=173), those receiving mycophenolate mofetil (MMF) had more severe baseline disease, included more patients of African descent, and were administered higher baseline steroid doses compared with those receiving azathioprine (AZA) or methotrexate (MTX). BILAG responses at week 12 were MMF 35%, AZA 49%, MTX 34%, and no immunosuppressant (NIS) 65%. At week 52, MMF response rates increased to 41% despite reducing the steroid doses, but fell in all others (p=0.07, adjusted for steroids). Patients with severe disease activity at baseline (SDAB) who were defined as ≥1 BILAG A (severe) organ score had lower response rates to AZA or MTX but higher rates to MMF or NIS. Interim flares were highest with MMF [flares/patient-year (pt-yr)]. For all flares, rates were as follows: AZA 1.24, MMF 1.87, MTX 1.42, and NIS 0.81 and severe flares were as follows: AZA 0.66, MMF 1.29, MTX: 1.20, and NIS 0.55. Interim flares occurred in 71% of MMF-endpoint responders, 54% of AZA, 50% of MTX, and 22% of NIS. Patients with SDAB had more flares than moderate patients in the MMF and MTX groups: MMF: 2.39 vs. 1.03 flares/pt-yr (p=0.01), MTX: 2.33 vs. 0.63 (p=0.0002), severe flares: 1.87 vs. 0.34 for MMF (p=0.0013), 2.13 vs. 0.40 for MTX (p<0.0001). In nephritis trials (n=808), MMF subjects received less steroids than intravenous cyclophosphamide and response rates were similar, but MMF-treated patients had fewer severe flares (p=0.03). CONCLUSION: Compared with MMF, AZA and MTX were associated with lower response rates at week 52. AZA-treated subjects had fewer flares and remained more stable in trials while engendering lower placebo plus SOC responses. MMF-treated subjects had frequent responses but more flares, suggesting that flares should be included in endpoint definitions. Given the likelihood of treatment selection bias, these data do not provide conclusions regarding efficacy but may help future trial designs by distinguishing factors definable at entry that are predictive of outcomes.

Work disability, lost productivity and associated risk factors in patients diagnosed with systemic lupus erythematosus.

OBJECTIVE: To assess prevalence and correlates of work presenteeism, absenteeism and work disability (WD) in patients with systemic lupus erythematous (SLE) and matched controls. METHODS: Patients with SLE from six medical centres were recruited to complete a questionnaire consisting of several prevalidated survey instruments. The subject's rheumatologist completed medical history. Subjects recruited two non-SLE 'best friend' controls with matching demographics to complete a control survey. Analyses employed Student's t tests, χ(2) tests and logistic regression models. RESULTS: 344 subjects with SLE and 322 controls submitted completed questionnaires. Mean pain, fatigue, Brief Cognitive Symptoms Index (BCSI) scores and depressive symptoms were worse in patients with SLE with WD (all p<0.01). WD was associated with African-American race, older age (51-65 years) and less than 4-year college education (all p<0.01). High presenteeism was associated with low pain and fatigue levels, higher BCSI scores and negatively correlated with depressive symptoms (all p<0.05). Increased pain and fatigue were associated with elevated absenteeism (p<0.05). Subjects with physically and cognitively demanding work reported worse presenteeism compared with controls with similar jobs (77% vs 85%, p<0.05 and 75% vs 85%, p<0.001), respectively. Patients with most cognitively demanding jobs reported greater weekly absenteeism (mean, 5.9 h) compared with controls (mean, 6.9 overtime hours, p<0.05). CONCLUSIONS: The questionnaire demonstrated increased WD in SLE. Highly physical and highly cognitive jobs are challenging to patients with SLE and had increased absenteeism compared with controls. Depressive symptoms were correlated with better presenteeism without major socio-demographic determinants. Employability may be enhanced by improving treatment of depressive symptoms in patients with SLE.