Ab0982 Domains for Inclusion in a Novel Treatment Response Measure for Systemic Lupus Erythematosus (Trm-Sle): Results of a Modified Delphi Study

Background: The Treatment Response Measure for Systemic Lupus Erythematosus (TRM-SLE) is a novel clinical outcome assessment (COA) to define meaningful improvement in disease activity for the purpose of SLE randomised clinical trials (RCTs), being developed by an international taskforce of clinicians, patient partners and industry representatives. To support regulatory approval of new treatments, contemporary guidelines require that clinical trials must demonstrate treatment benefit relevant to how patients "feel, function or survive", as measured by COAs specific for the RCT context of use 1. Objectives: The aim of this study was to establish consensus on the outcome domains with which to define meaningful improvement in disease activity in the novel TRM-SLE instrument, considering both patient and clinician perspectives as well as clinical trial utility. Methods: Candidate domains identified by surveying 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 clinicians and patient partners rated domain "importance" (impact on SLE symptoms, function or survival). In Stage 2, clinicians rated "important" domains on three further characteristics relevant to RCT utility: "appropriateness" for evaluating disease activity, "representation" among patients with active SLE, and "measurability" in an RCT context. Ratings of "importance" and "representation" were supported by the results of targeted literature reviews. The prespecified consensus threshold for each Delphi round was a rating of 7 or more (0-9) by at least 70% of participants, with consensus on all four characteristics rated across the two Delphi stages required for inclusion in TRM-SLE. Results: The domain generation survey completed by 36/59 (61%) TRM-SLE Taskforce members yielded 34 candidate outcome domains. Of 118 invitees to the modified Delphi study, 87/102 (85%) clinicians with a median (IQR) of 21 (11, 30) years' experience and 13/16 (81%) patient partners with median (IQR) disease duration 19 (16,33) years completed at least one Delphi round, with representation from six continents. In Stage 1, 14 domains met consensus on "importance" in both clinician and patient groups, and 11 domains met consensus on "importance" amongst patients only (Table 1). These 25 "important" domains were rated in Stage 2, after which eight domains (alopecia, arthritis, haemolytic anaemia, mucosal ulcers, nephritis, rash, serositis and thrombocytopenia) also reached consensus on all of "appropriateness", "representation" and "measurability" (Table 2). Notably, two domains ultimately meeting consensus for inclusion in TRM-SLE were rated "important" in Stage 1 by patients only, highlighting the vital contribution of the patient perspective. Conclusion: We reached consensus on eight domains (alopecia, arthritis, haemolytic anaemia, mucosal ulcers, nephritis, rash, serositis and thrombocytopenia) which will define meaningful change in disease activity in TRM-SLE, considering patient and clinician perspectives on importance, and utility in an RCT context. In the next stage of the TRM-SLE project working groups will reach consensus on the measurement, scoring and thresholds defining response for each of these domains. REFERENCES: 1 FDA Patient Focused Drug Development Guidance: Selecting, Developing or Modifying Fit-for-Purpose Clinical Outcome Assessments. https://www.fda.gov/media/159500/download Table 1. Proportion of participants rating domains highly based on "importance", defined as being associated with how a patient feels, functions or survives when assessing treatment effect in an SLE clinical trial, after two Delphi voting rounds. Table 2. Proportion of participants rating "important" domains highly on "appropriateness", "representation" and "measurability" when assessing treatment effect in an SLE clinical trial, after two Delphi voting rounds. Acknowledgements: We would like to acknowledge all members of the TRM-SLE Taskforce and those who generously contributed their time and expertise to our Delphi study. Disclosure of Interests: Kathryn Connelly: None declared, Rachel Koelmeyer: None declared, Darshini Ayton: None declared, John May: None declared, Kate Gregory: None declared, Laura Eades: None declared, Raychel Barallon: None declared, Rangi Kandane-Rathnayake GSK, Novartis (Institutional research grants), Vera Golder: None declared, Afia Anzum: None declared, Maisarah Mydin: None declared, Munni Akther: None declared, Alan Friedman Abbvie, Anca Askanase Investigator/Consultant for Abbvie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer and UCB, Cynthia Aranow AstraZeneca, GSK, Kezar Inc, Bristl Myers Squibb, Kezar Inc., Edward M. Vital Novartis, AstraZeneca, UCB, Novartis, Roche, Pfizer, UCB, AstraZeneca, Novartis, Abbvie, Merck, Lilly, Otsuka, AstraZeneca, Sandoz, Guillermo Pons-Estel Boehringer Ingelheim, GSK, Janssen, Novartis and Pfizer, AstraZeneca, Boehringer Ingelheim, GSK, Janssen, Novartis, Pfizer and RemeGen, Janssen, Hermine Brunner AZ, BI, Novartis, Pfizer, UCB, BMS, TAKEDA, Kenneth C. Kalunian BMS, GSK, Artiva, Cabaletta Bio, Roche/Genentech, AstraZeneca, Artiva, Eli Lilly, Kezar, Aurinia, Abbvie, Khadija Dantata: None declared, Laurent Arnaud Alexion, Amgen, Astra-Zeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, Cêmka, GSK, Grifols, Janssen, LFB, Lilly, Menarini France, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, Sêmeia, UCB, Laurie Burke Multiple across many different therapeutic areas; no active consulting in SLE., Lee Simon: None declared, Qing Zuraw: None declared, Sandra Garces Amgen, Amgen- Executive role, Victoria Werth Gilead, Lilly, BMS, Nektar, Abbvie, Akira, Viela, GSK, EMD Serona, Sanofi, Xencor, ONO, Cabaletta, Pfizer, Corbus, Amgen, Janssen, Biogen, Gilead, Viela, Ventus, Regeneron, Argenx, Ying Sun Yes, Merck KGaA, Darmstadt, Germany, Yoshiya Tanaka Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho, Mitsubishi-Tanabe, Eisai, Chugai, Taisho, Youmna Lahoud Biogen, Biogen, Alain Cornet: None declared, Alessandro Sorrentino: None declared, Anisur Rahman Lilly, Anna Stevens Multiple - Abbvie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer and UCB, Catherine Barbey Biogen, Biogen, Dzifa Dey Pfizer, Roche, Elaine Karis Amgen Inc, Amgen Inc, Eloisa Bonfa: None declared, Erika Noss Johnson and Johnson Innovative Medicine, Eve MD Smith: None declared, George Stojan UCB, Jeanette Andersen: None declared, Joan Merrill UCB, GlaxoSmithKline, Abbvie, EMD Serono, Janssen, Lilly, Genentech, Aurinia, Provention, Remegen, Celgene/Bristo Myers Squibb, AstraZeneca, Amgen, Astellas, Alexion, Sanofi, Zenas, Joseph F. Merola Consultant and/or investigator for multiple complanies - Amgen, Astra-Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Incyte, Moonlake, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma, Jorge A. Ross Terres Genentech/Roche, Genentech/Roche, Joy Buie Novartis, Aurinia, Justine Maller Genentech/Roche, Genentech/Roche, Karen Costenbader BMS, GSK, Cabaletta Bio, Merck, Gilead, Marta Mosca GSK, Astra Zeneca, Janssen, ASTRA ZENECA, ABBVIE, UCB, GKS, OTSUKA, GSK, Maja Hojnik Eli Lilly and Company (Lilly), Maria Dall'Era Genentech, Aurinia, GSK, AstraZeneca, Janssen, Nikolay Delev BMS, Richard A. Furie AZ; GSK, BMS, GSK, Genentech, AZ, Biogen, GMS, GSK, Genentech, Biogen, Kyverna, Ronald F. van Vollenhoven AbbVie, AstraZeneca, BMS, Galapagos, GSK, Janssen, Pfizer, UCB, AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, Pfizer, RemeGen, UCB, AstraZeneca, BMS, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Subhashis Banerjee BMS, BMS, Eric Morand AstraZeneca, Merck, Gilead, Roche, EMD Serono, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Genentech, GlaxoSmithKline, Janssen, Novartis, AbbVie, Galapagos, IgM, AbbVie, Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, EMD Serono, Genetech, GSK, Janssen, UCB (all institutional).