2262: Identifying Important Domains for Inclusion in a Novel Treatment Response Measure for Systemic Lupus Erythematosus (TRM-SLE): Results of a Modified Delphi Study

Kathryn Connelly¹, Rachel Koelmeyer¹, Darshini Ayton¹, Raychel Barrallon¹, Laura Eades², Vera Golder³, Kate gregory¹, John May¹, Rangi Kandane-Rathnayake³, Maisarah Mydin¹, Munni Akther¹, Afia Anzum¹, Jeanette Andersen⁴, Hermine Brunner⁵, Cynthia Aranow⁶, Laurent Arnaud⁷, Anca Askanase⁸, Catherine Barbey⁹, Joy Buie¹⁰, Laurie Burke¹¹, Alain Cornet¹², Karen Costenbader¹³, Maria Dall'Era¹⁴, Joan Merrill¹⁵, Khadija Dantata¹⁶, Alan Friedman¹⁷, Richard Furie¹⁸, Sandra Garces¹⁹, Maja Hojnik²⁰, Kenneth Kalunian²¹, Justine Maller²², Patrick Marquis²³, Marta Mosca²⁴, Erika Noss²⁵, Guillermo Pons-Estel²⁶, Lee Simon²⁷, Eve Smith²⁸, Alessandro Sorrentino²⁹, Anna Stevens³⁰, George Stojan³¹, Ying Sun³², Yoshiya Tanaka³³, Ed Vital³⁴, Ronald van Vollenhoven³⁵, Victoria P. Werth³⁶ and Eric Morand³⁷, ¹Monash University, Clayton, Australia, ²Monash Health and Monash University, Clayton, Australia, ³Monash University, Department of Medicine, Sub-faculty of Clinical and Molecular Medicine, Clayton, Australia, ⁴Lupus Europe, Knebel, Denmark, ⁵Cincinnati Children's Hospital Medical Center, Division of Rheumatology, Cincinnati, OH, ⁶Feinstein Institutes for Medical Research, Manhasset, NY, ⁷University Hospitals of Strasbourg, Strasbourg, France, ⁸Columbia University Medical Center, New York, NY, ⁹Biogen, Baar, Switzerland, ¹⁰Lupus Foundation of America, York, SC, ¹¹LORA Group, Normal, IL, ¹²Lupus Europe, Brussels, Belgium, ¹³Brigham and Women's Hospital and Harvard Medical School, Boston, MA, ¹⁴University of California San Francisco, San Francisco, CA, ¹⁵Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹⁶Lupus Foundation of America, Richmond Hill, GA, ¹⁷AbbVie, Inc., North Chicago, IL, ¹⁸Northwell Health, Manhasset, NY, ¹⁹Amgen, Inc., Thousand Oaks, CA, ²⁰Eli Lilly and Company, Indianapolis, IN, ²¹University of California San Diego, La Jolla, CA, ²²Genentech, Inc., Half Moon Bay, CA, ²³Modus Outcomes, Newton, MA, ²⁴Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, ²⁵Janssen Research and Development, Dresher, PA, ²⁶CREAR, Rosario, Argentina, ²⁷SDG LLC, West Newton, MA, ²⁸University of Liverpool, Liverpool, United Kingdom, ²⁹Medical Affairs, AstraZeneca, Cambridge, United Kingdom, ³⁰Bristol Myers Squibb, Groton, CT, ³¹UCB, Baltimore, MD, ³²the healthcare business of Merck KGaA, Darmstadt, Germany, ³³University of Occupational and Environmental Health, Kitakyushu, Japan, ³⁴University of Leeds, Leeds, United Kingdom, ³⁵Amsterdam University Medical Centers, Amsterdam, Netherlands, ³⁶University of Pennsylvania, Wynnewood, PA, ³⁷Monash University, Centre for Inflammatory Diseases, Melbourne, Australia

Background/Purpose: The Treatment Response Measure for Systemic Lupus Erythematosus (TRM-SLE) is a novel clinical outcome assessment (COA) for SLE randomized controlled trials (RCTs), being developed by an international clinician-industry-patient taskforce. Current COA development guidelines require that outcome measures used in RCTs should capture treatment effects relevant to how patients "feel, function or survive" to support regulatory approval (1). The aim of this study was to identify domains to be considered for inclusion in TRM-SLE from the perspective of expert SLE clinicians and patients based on this paradigm.

Methods: Candidate domains were identified via surveying a multinational panel of clinicians, patients and industry representatives. Domains were then rated in a modified Delphi study (two online survey rounds separated by a discussion meeting) in which clinicians with SLE expertise and patient advisory panellists were invited to rate the "importance" of candidate domains on a 1-9 scale (where 1 = not important and 9 = critically important). Importance was defined as domain activity having an impact on how a patient "feels, functions or survives", when assessing response to treatment in an SLE RCT. A literature review summarising associations of each candidate domain with key SLE symptoms, functional impact, damage and mortality was provided to participants to support participant ratings. The consensus threshold was prespecified as a rating of at least 7 by 70% of participants in both clinician and patient groups.

Results: The domain generation survey yielded 64 nominations, grouped into a core list of 34 candidate domains. Of 118 invitees to the modified Delphi study, 87 clinicians with a median (interquartile range; IQR) of 21 (11, 30) years' experience and 13 patients/representatives with a median (IQR) disease duration of 19 (16,33) years participated, with representation from six continents. Of the 34 candidate domains, 6 met the consensus threshold after Round 1 of voting, increasing to 14 after Round 2 (Table 1). An additional 11 domains met consensus in the patient group only. Notably, some domains meeting consensus on importance (e.g. fatigue) are not measured in current primary SLE trial endpoints, while others (e.g. anti-dsDNA, complement) included in current response measures did not reach consensus for inclusion.

Conclusion: When rated for importance, consensus was reached in both SLE clinician and patient groups on multiple candidate domains for inclusion in a novel COA for SLE trials. Discrepancies between clinician and patient perspectives were also identified. Important domains will next be rated on other characteristics relevant to inclusion in a COA (appropriateness, representation and measurability), with selected domains to proceed to definition of response measurement.

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




K. Connelly: AstraZeneca, 2; R. Koelmeyer: None; D. Ayton: None; R. Barrallon: None; L. Eades: None; V. Golder: None; K. gregory: None; J. May: None; R. Kandane-Rathnayake: None; M. Mydin: None; M. Akther: None; A. Anzum: None; J. Andersen: None; H. Brunner: AbbVie, 2, AstraZeneca-Medimmune, 2, Biogen, 2, Boehringer-Ingelheim, 2, Bristol-Myers Squibb (BMS), 2, 5, Celgene, 2, Eli Lilly, 2, 5, EMD Serono, 2, F-Hoffman La Roche, 2, 5, GlaxoSmithKlein (GSK), 2, 5, 6, Horizon, 2, 2, Janssen, 5, Merck, 2, Novartis, 2, 5, 6, Pfizer, 2, 5, 6; C. Aranow: AstraZeneca, 2, Bristol-Myers Squibb(BMS), 2, GlaxoSmithKlein(GSK), 2, 5, kezar Inc, 2; L. Arnaud: AbbVie, 6, Alexion, 6, Alpine, 2, 6, Amgen, 6, AstraZeneca, 1, 2, 6, Biogen, 6, Boehringer Ingelheim, 6, Bristol-Myers Squibb(BMS), 2, 6, Eli Lilly, 6, GlaxoSmithKlein(GSK), 1, 2, 6, Grifols, 6, Janssen, 6, Kezar Life Sciences, 2, 6, LFB, 6, Medac, 6, Novartis, 2, 6, Pfizer, 6, Roche-Chugaï, 6, UCB, 6; A. Askanase: AbbVie, 2, Amgen, 2, AstraZeneca, 2, Aurinia, 2, Bristol-Myers Squibb, 2, Celgene, 2, Eli Lilly, 2, Genentech, 2, GSK, 2, Idorsia, 2, Janssen, 2, Mallinckrodt, 2, Pfizer, 2, UCB Pharma, 2; C. Barbey: Biogen, 3, 11; J. Buie: None; L. Burke: Amgen, 1, Biogen, 1; A. Cornet: None; K. Costenbader: Amgen, 2, 5, AstraZeneca, 5, Bristol-Myers Squibb(BMS), 2, Cabaletta, 2, Eli Lilly, 2, Exagen Diagnostics, 5, Gilead, 5, GlaxoSmithKlein(GSK), 2, 5, Janssen, 2, 5; M. Dall'Era: Annexon Biosciences, 2, 5, AstraZeneca, 2, Aurinia, 2, Biogen, 2, GlaxoSmithKlein, 2, 5, Pfizer, 2; J. Merrill: AbbVie, 2, Alexion, 2, Alumis, 2, Amgen, 2, AstraZeneca, 2, 5, Aurinia, 2, Bristol Myers Squibb, 2, 5, EMD Serono, 2, Genentech, 2, Gilead, 2, GlaxoSmithKline, 2, 5, Lilly, 2, Merck, 2, Pfizer, 2, Provention, 2, Remegen, 2, Sanofi, 2, UCB Pharma, 2, Zenas, 2; K. Dantata: None; A. Friedman: AbbVie, 3, 11; R. Furie: Biogen, 2, 5; S. Garces: Amgen, 3, 11; M. Hojnik: None; K. Kalunian: AbbVie/Abbott, 2, Amgen, 5, AstraZeneca, 2, Aurinia, 2, Bristol-Myers Squibb(BMS), 2, Eli Lilly, 2, EquilliumBio, 2, Genentech, 2, Gilead, 2, Janssen, 2, KezarBio, 1, Merck/MSD, 2, Novartis, 2, Pfizer, 2, Remegene, 2, Roche, 2, UCB, 5; J. Maller: Genentech, 3; P. Marquis: Alexion, 2, Biogen, 2, Eli Lilly, 2, GlaxoSmithKlein(GSK), 2, Mitsubishi Tanabe Pharma, 2, Otsuka, 2, Takeda, 2, UCB, 2; M. Mosca: AstraZeneca, 2, Bristol-Myers Squibb(BMS), 2, Eli Lilly, 2, GlaxoSmithKlein(GSK), 2, Otsuka, 2, UCB, 2; E. Noss: Janssen, 3; G. Pons-Estel: GlaxoSmithKlein(GSK), 1, 5, 6, Janssen, 1, 5, 6, Novartis, 1, 6, Pfizer, 5, 6, Werfen/Inova, 5, 6; L. Simon: Horizon, 2, 7, Pfizer, 2, 12, Member of DSMB; E. Smith: None; A. Sorrentino: AbbVie/Abbott, 12, Own stocks, AstraZeneca, 3, Galapagos, 12, Own stocks, Gilead, 12, Own stocks, Moderna, 12, Own stocks; A. Stevens: Bristol-Myers Squibb(BMS), 3, 11; G. Stojan: UCB Pharma, 3, 11; Y. Sun: The healthcare business of Merck KGaA, Darmstadt, Germany, 3; Y. Tanaka: AbbVie, 6, AstraZeneca, 6, BMS, 6, Boehringer-Ingelheim, 6, Chugai, 5, 6, Eisai, 5, 6, Eli Lilly, 6, Gilead, 6, GSK, 6, Mitsubishi-Tanabe, 5, Pfizer, 6, Taiho, 6, Taisho, 5, 6; E. Vital: F. Hoffmann-La Roche Ltd, 2, Genentech, Inc., 2, Sandoz, 5; R. van Vollenhoven: AbbVie, 2, 6, AstraZeneca, 2, 5, 6, Biogen, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, Galapagos, 2, 5, 6, GlaxoSmithKline, 6, Janssen, 2, 6, MSD/Merck Sharp and Dohme, 5, Novartis, 5, Pfizer, 2, 5, 6, RemeGen, 2, Roche, 5, Sanofi, 5, UCB, 2, 5, 6; V. Werth: AbbVie, 2, Amgen, 2, 5, Anaptysbio, 2, Argenx, 5, AstraZeneca, 2, Biogen, 2, 5, Bristol Myers Squibb, 2, Celgene, 2, 5, Corbus, 5, CSL Behring, 2, 5, EMD Serono, 2, Galderma, 2, Genentech, 5, Gilead, 2, 5, GlaxoSmithKline, 2, Horizon Therapeutics, 5, Idera, 2, Incyte, 2, Janssen, 2, Kyowa Kirin, 2, Lilly, 2, MedImmune, 2, Medscape, 2, Merck, 2, Nektar, 2, Novartis, 2, Octapharma, 2, Pfizer, 2, 5, Principia, 2, Regeneron, 5, Resolve, 2, 2, Rome Therapeutics, 2, 5, Sanofi, 2, Ventus, 5, Viela, 2, 5, Xencor, 2; E. Morand: AbbVie, 2, 5, Amgen, 5, AstraZeneca, 2, 5, 6, Biogen, 2, 5, Bristol Myers Squibb, 2, 5, Eli Lilly, 2, 5, EMD Serono, 2, 5, Galapagos, 2, Genentech, 2, 5, GlaxoSmithKline, 2, 5, IgM, 2, Janssen, 2, 5, Novartis, 2, Servier, 2, Takeda, 2, UCB, 5.