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. 2025 May 6;12(1):e001484.
doi: 10.1136/lupus-2024-001484.

Domains for inclusion in a novel Treatment Response Measure for Systemic Lupus Erythematosus (TRM-SLE): results of a modified Delphi study

Kathryn Connelly #  1 , Rachel Koelmeyer #  2 , Darshini Ayton  3 , John May  1 , Kate Gregory  1 , Laura E Eades  1 , Raychel Barallon  1 , Rangi Kandane-Rathnayake  4 , Vera Golder  1 , Afia Anzum  1 , Maisarah Mydin  1 , Munni Akther  1 , Alan Friedman  5 , Anca D Askanase  6 , Cynthia Aranow  7 , Edward Vital  8 , Guillermo Pons-Estel  9 , Hermine Brunner  10 , Kenneth Kalunian  11 , Khadija Dantata  12 , Laurent Arnaud  13   14 , Laurie Burke  15 , Lee S Simon  16 , Qing Zuraw  17 , Sandra Garces  18 , Victoria P Werth  19 , Ying B Sun  20 , Yoshiya Tanaka  21 , Youmna Lahoud  22 , Alain Cornet  23 , Alessandro Sorrentino  24 , Anisur Rahman  25 , Anna Stevens  26 , Catherine Barbey  27 , Ida Dzifa Dey  28 , Elaine Karis  18 , Eloisa Bonfá  29 , Erika Noss  30 , Eve M D Smith  31 , George Stojan  32 , Jeanette Andersen  23 , Joseph F Merola  33   34 , Jorge A Ross Terres  35 , Joy Buie  36 , Justine Maller  35 , Marta Mosca  37 , Maja Hojnik  38 , Maria Dall'Era  39 , Richard A Furie  40 , Ronald F van Vollenhoven  41 , Subhashis Banerjee  26 , Eric Morand  42   43 ; TRM-SLE Taskforce Members; Delphi Participants
Collaborators, Affiliations

Domains for inclusion in a novel Treatment Response Measure for Systemic Lupus Erythematosus (TRM-SLE): results of a modified Delphi study

Kathryn Connelly et al. Lupus Sci Med. .

Abstract

Objectives: To achieve consensus on domains of active disease for inclusion in a novel outcome measure for SLE randomised controlled trials (RCTs), the Treatment Response Measure for SLE (TRM-SLE).

Methods: Domains nominated by TRM-SLE Taskforce members were rated in a two-stage modified Delphi study. Each stage comprised two online survey rounds separated by a structured discussion meeting. In Stage 1, expert lupus clinicians and patient representatives rated domain 'importance' (impact on symptoms, function or survival). In Stage 2, clinicians rated 'important' domains on three characteristics relevant to RCT utility: 'appropriateness' for evaluating change in disease activity, 'representation' in patients with active SLE and 'measurability' in an RCT context. Consensus for domain inclusion was prespecified as all four characteristics achieving a rating ≥7 on a 1-9 scale by ≥70% of participants.

Results: Domain nominations from 36/59 (61%) TRM-SLE Taskforce members yielded 34 potential domains which were rated in the modified Delphi study. At least one Delphi round was completed by 87 clinicians and 13 patient representatives. In Stage 1, 14 domains met consensus on 'importance' in both clinician and patient groups, and 11 domains met consensus among patients only. After Stage 2, eight of these domains also reached consensus on 'appropriateness', 'representation' and 'measurability': alopecia, arthritis, haemolytic anaemia, nephritis, mucosal ulcers, rash, serositis and thrombocytopenia.

Conclusions: Considering patient and clinician perspectives, we reached consensus to include eight disease activity domains for future development into the novel TRM-SLE clinical trial outcome measure, aiming to improve trial interpretability and success.

Keywords: Clinical Trial; Patient Reported Outcome Measures; Severity of Illness Index; Systemic Lupus Erythematosus.

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Conflict of interest statement

Competing interests: RK reports grants/research support from GSK and Novartis. AF reports shares in AbbVie and consulting fees from Eli Lilly, Merck, Sun Pharmaceuticals and Tenet, and previous employment by AbbVie. AA reports consulting fees from AbbVie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer and UCB. CA reports consulting fees from Synthekine, Bristol Myers Squibb, Kezar, AstraZeneca, GSK and received grants/research support from GSK. EV reports speaker fees from AstraZeneca, UCB, Novartis; consulting fees from Roche, Pfizer, UCB, AstraZeneca, Novartis, AbbVie, Merck, Lilly, Otsuka and grants/research support from AstraZeneca and Sandoz. GP-E reports grants, consulting fees and participation as a speaker and/or advisor and/or steering committee for: Alumis, AstraZeneca, Boehringer Ingelheim, GSK, Janssen, Novartis, Pfizer, RemeGen, Sanofi and Werfen Diagnostics. HB reports consulting fees from AstraZeneca, BI, Novartis, Pfizer, UCB, BMS, Takeda, Eli Lilly, J&J, Biogen and received grants/research support from Pfizer. KK reports consulting fees from BMS, GSK, Artiva, Cabaletta Bio, Roche/Genentech, AstraZeneca, Artiva, Eli Lilly, Kezar, Aurinia and AbbVie. LA reports consulting fees from Alexion, Amgen, AstraZeneca, AbbVie, Alpine Pharmaceuticals, Biogen, BMS, Boehringer Ingelheim, Chugai, GSK, Grifols, Janssen, Kezar, LFB, Lilly, Menarini France, Medac, Novartis, Pfizer, Roche, UCB. LB reports consulting fees from multiple companies across many different therapeutic areas; with no active consulting in SLE. SG reports shares in Amgen and employment by Amgen. QZ reports shares in Remegen Biosciences and employment by Remegen Biosciences, and previous employment by Janssen. VPW reports consulting fees from Pfizer, Janssen, Neovacs, Idera, Octapharma, CSL Behring, Corbus, Rome, AstraZeneca, Biogen, Celgene, Gilead, Lilly, BMS, Nektar, AbbVie, Akira, Viela, GSK, EMD Serona, Sanofi, Xencor, ONO, Cabaletta and received grants/research support from Pfizer, Corbus, Amgen, Janssen, Biogen, Gilead, Viela, Ventus, Regeneron, Argenx. YBS reports employment at Merck KGaA. YT reports speaker fees from Eli Lilly, AstraZeneca, AbbVie, Gilead, Chugai, Boehringer Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol Myers, Pfizer, Taiho and grants/research support from Mitsubishi Tanabe, Eisai, Chugai, Taisho. YL reports shares in Biogen and is an emplyoee of Biogen. ASo reports shares in Galapagos and is an employee of Sanofi and previous employee of AstraZeneca. AR reports speaker fees from Elli Lilly. ASt reports consulting fees from AbbVie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer and UCB. CB reports shares in Biogen and is an emplyoee of Biogen. IDD reports speaker fees from Pfizer, Roche. EK reports shares in Amgen and is an emplyoee of Amgen. EN reports shares in Johnson and Johnson and is an employee of Janssen Research and Development, a Johnson and Johnson company. GS reports shares in UCB. JFM reports consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Moonlake, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma. JART reports shares in Genentech/Roche and is an emplyoee of Genentech/Roche. JB reports consulting fees from Novartis and grants/research support from Aurinia. JMal reports shares in Genentech/Roche and is an emplyoee of Genentech/Roche. MMo reports speaker fees for GSK, AstraZeneca, Janssen; consulting fees from AstraZeneca, AbbVie, UCB, GSK, Otsuka and grants/research support from GSK. MH reports shares in Eli Lilly. MD’E reports consulting fees from Genentech, Aurinia, GSK, AstraZeneca, Janssen. RAF reports speaker fees from AZ, GSK; consulting fees from BMS, GSK, Genentech, AstraZeneca and Biogen, and received grants/research support from GMS, GSK, Genentech, Biogen, Kyverna. RFvV reports speaker fees from AbbVie, AstraZeneca, BMS, Galapagos, GSK, Janssen, Pfizer, UCB; consulting fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, Pfizer, RemeGen, UCB and; grants/research support from AstraZeneca, BMS, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. SB reports shares in BMS and is an emplyoee of BMS. EM reports speaker fees from AstraZeneca, Merck, Gilead, Roche; consulting fees from EMD Serono, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Genentech, GlaxoSmithKline, Janssen, Novartis, AbbVie, Galapagos, IgM and grants/research support from AbbVie, Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB (all institutional). The remaining authors have no disclosures.

Figures

Figure 1
Figure 1. Overview of the domain selection process, in the context of the five stages of TRM-SLE instrument development. TRM-SLE, Treatment Response Measure for SLE.
Figure 2
Figure 2. Domain generation process and participants. SLEDAI, SLE Disease Activity Index; TRM-SLE, Treatment Response Measure for SLE.
Figure 3
Figure 3. Detailed results from the two-stage Delphi study for the eight domains meeting consensus on all four characteristics: ‘importance’, ‘appropriateness’, ‘representation’ and ‘measurability’. Full results for all domains are provided in the online supplemental material. Red ≤30% agreement, yellow >30–<70% agreement, green ≥70% agreement. DI, disagreement index (<1 indicates high agreement).
Figure 4
Figure 4. Detailed results from the two-stage Delphi study for example domains that did not meet consensus for inclusion in our novel instrument. Full results for all domains are provided in the online supplemental material. Red ≤30% agreement, yellow >30–<70% agreement, green ≥70% agreement. DI, disagreement index (<1 indicates high agreement).
Figure 5
Figure 5. Summary of domain selection outcomes based on ratings of ‘importance’, ‘appropriateness’, ‘representation’ and ‘measurability’ and potential implications for domain measurement in clinical trials.
See this image and copyright information in PMC

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