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Meta-Analysis
. 2022 Jul;81(7):979-989.
doi: 10.1136/annrheumdis-2021-222054. Epub 2022 Apr 7.

Development and preliminary validation of the Sjögren's Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjögren's syndrome

Raphaele Seror  1   2 , Gabriel Baron  3   4 , Marine Camus  5   2 , Divi Cornec  6   7 , Elodie Perrodeau  3   4 , Simon J Bowman  8   9   10 , Michele Bombardieri  11 , Hendrika Bootsma  12 , Jacques-Eric Gottenberg  13   14 , Benjamin Fisher  15   16 , Wolfgang Hueber  17 , Joel A van Roon  18 , Valérie Devauchelle-Pensec  6   7 , Peter Gergely  19 , Xavier Mariette #  5   2 , Raphael Porcher #  3   4 ; NECESSITY WP5 - STAR development working group; NECESSITY WP5- STAR development working group
Collaborators, Affiliations
Meta-Analysis

Development and preliminary validation of the Sjögren's Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjögren's syndrome

Raphaele Seror et al. Ann Rheum Dis. 2022 Jul.

Abstract

Objective: To develop a composite responder index in primary Sjögren's syndrome (pSS): the Sjögren's Tool for Assessing Response (STAR).

Methods: To develop STAR, the NECESSITY (New clinical endpoints in primary Sjögren's syndrome: an interventional trial based on stratifying patients) consortium used data-driven methods based on nine randomised controlled trials (RCTs) and consensus techniques involving 78 experts and 20 patients. Based on reanalysis of rituximab trials and the literature, the Delphi panel identified a core set of domains with their respective outcome measures. STAR options combining these domains were proposed to the panel for selection and improvement. For each STAR option, sensitivity to change was estimated by the C-index in nine RCTs. Delphi rounds were run for selecting STAR. For the options remaining before the final vote, a meta-analysis of the RCTs was performed.

Results: The Delphi panel identified five core domains (systemic activity, patient symptoms, lachrymal gland function, salivary gland function and biological parameters), and 227 STAR options combining these domains were selected to be tested for sensitivity to change. After two Delphi rounds, a meta-analysis of the 20 remaining options was performed. The candidate STAR was then selected by a final vote based on metrological properties and clinical relevance.

Conclusion: The candidate STAR is a composite responder index that includes all main disease features in a single tool and is designed for use as a primary endpoint in pSS RCTs. The rigorous and consensual development process ensures its face and content validity. The candidate STAR showed good sensitivity to change and will be prospectively validated by the NECESSITY consortium in a dedicated RCT.

Keywords: Sjogren's syndrome; outcome assessment, health care; patient reported outcome measures.

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Conflict of interest statement

Competing interests: RS has received consulting fees from GlaxoSmithKline, Boehringer, Janssen and Novartis, participated in an advisory board for Janssen, and received support for attending meeting from GlaxoSmithKline and Amgen. DC has received consulting fees from GlaxoSmithKline, Bristol Myers Squibb, Janssen, Amgen, Pfizer and Roche. J-EG has received honoraria from AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, Sanofi, Novartis, MSD, CSL Behring and Genzyme and received grant from Bristol Myers Squibb. SJB and BF receive funding from the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Birmingham, UK. SJB has provided consultancy services in the field of clinical trial design for Sjögren’s syndrome for AbbVie, AstraZeneca, Galapagos and Novartis Pharmaceuticals in 2018–2021. BF has received grants from Servier, Galapagos and Janssen, provided consultancy services for Novartis, Bristol Myers Squibb, Janssen and Servier, and received honoraria from Bristol Myers Squibb and Novartis. MB has received grants from Amgen/MedImmune, Janssen and GlaxoSmithKline, and personal fees from UCB, Amgen/MedImmune, Janssen and GlaxoSmithKline. HB has received grants from Bristol Myers Squibb and Roche, and consulting fees from Bristol Myers Squibb, Roche, Novartis, MedImmune and Union Chimique Belge. WH and PG are employees of Novartis Pharma and recipients of Novartis stocks. XM has received a grant from Ose Pharmaceuticals and consultancy fees from Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB. GB, MC, EP, JAvR, VD-P and RP declare no competing interests.

Figures

Figure 1
Figure 1
STAR development process. STAR, Sjögren’s Tool for Assessing Response.
Figure 2
Figure 2
Sensitivity to change of each individual outcome in the combined analysis of the TEARS and TRACTISS rituximab trials. Sensitivity to change is represented by the Cohen’s effect size and the 95% CI. Analyses relied on a combined analysis of data from TEARS and TRACTISS rituximab trials. Cohen’s effect size and 95% CI for the standardised difference in mean change from baseline to W24 were computed for each outcome in the four responder subsets and in the whole population of the two trials. ESR, erythrocyte sedimentation rate; ESSDAI, EULAR Sjögren’s Syndrome Disease Activity Index; ESSPRI, EULAR Sjögren’s Syndrome Patient Reported Index; PtGA, patient global assessment; PhGA, physician global assessment; RF, rheumatoid factor; TEARS, Tolerance and Efficacy of Rituximab in primary Sjögren Syndrome; TRACTISS, TRial of Anti-B Cell Therapy In patients with primary Sjögren Syndrome; UWSF, unstimulated whole salivary flow; VAS, Visual Analogue Scale; W, duration in weeks.
Figure 3
Figure 3
Results of meta-analyses on six studies considered positive and three considered negative by the experts. Meta-analyses were performed for the 20 STAR options that reach the final step and are presented for binary endpoints (panel A) et continuous endpoints (panel B). Interpretation: a score that is sensitive to change and specific to the treatment should have a treatment effect close to the null effect in the negative trials and as far as possible from the null effect in the positive trials. cont, continuous; CRESS, Composite of Relevant Endpoints for Sjögren’s Syndrome; SMD, standardised mean difference; STAR, Sjögren’s Tool for Assessing Response; th5, threshold 5; th6, threshold 6; V, version.
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