Towards a Novel Clinician-Reported Outcome Measure for SLE - Outcomes of an International Consensus Process

Kathryn Connelly¹, Laura Eades², Rachel Koelmeyer³, Darshini Ayton³, Vera Golder², Rangi Kandane-Rathnayake², Kate Gregory-Wong³, Hussein Al-Mossawi⁴, Jeanette Andersen⁵, Cynthia Aranow⁶, Laurent Arnaud⁷, Anca Askanase⁸, Subhashis Banerjee⁹, Catherine Barbey¹⁰, Hermine Brunner¹¹, Joy Buie¹², Laurie Burke¹³, Alain Cornet¹⁴, Karen Costenbader¹⁵, Maria Dall'Era¹⁶, Khadija Dantata¹⁷, Nikolay Delev⁹, Ann Eldred¹⁸, Alan Friedman¹⁹, Richard Furie²⁰, Sandra Garces²¹, Dennis Grasela²², Heath Guay²³, Oliver Guenther²⁴, Maria Juarez²⁵, Shelly Kafka²⁶, Kenneth Kalunian²⁷, Elaine Karis²⁸, Youmna Lahoud²⁹, Catharina Lindholm³⁰, Jeffrey Lockman³¹, Charlotte Lupton³², Justine Maller³³, Ashley Marion³⁴, Patrick Marquis³⁵, Joan Merrill³⁶, Thomas Morel³⁷, Marta Mosca³⁸, Yulia Pincus³⁹, Samantha Pomponi⁴⁰, Guillermo Pons-Estel⁴¹, Jorge Ross Terres³³, Cailin Sibley⁴², Maria Silk⁴³, Sanjeev Roy⁴⁴, Lee S Simon⁴⁵, Alessandro Sorrentino⁴⁶, Christian Stach⁴⁷, George Stojan⁴⁸, Ying Sun²⁴, Yoshiya Tanaka⁴⁹, Erik Thomas⁵⁰, Ronald van Vollenhoven⁵¹, Cristina Vazquez Mateo⁵⁰, Edward M Vital⁵², Victoria Werth⁵³, Eric Zollars²⁸, Qing Zuraw⁵⁴ and Eric Morand⁵⁵, ¹Monash Health, Camberwell, Australia, ²Monash University, Clayton, Australia, ³Monash University, Melbourne, Australia, ⁴AstraZeneca, Bucks, United Kingdom, ⁵Lupus Europe, Lupus DK, EULAR PARE, ERN ReCONNECT, Brussels, Belgium, ⁶Feinstein Institutes for Medical Research, Manhasset, NY, ⁷Hautepierre Hospital, University Hospital of Strasbourg, Rheumatology, Strasbourg, France, ⁸Columbia University Medical Center, New York, NY, ⁹Bristol Myers Squibb, Princeton, NJ, ¹⁰Biogen, Baar, Switzerland, ¹¹Division of Rheumatology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Department of Pediatrics, Cincinnati, OH, ¹²Lupus Foundation of America, Charleston, SC, ¹³LORA Group, Royal Oak, MD, ¹⁴Lupus Europe, Brussels, Belgium, ¹⁵Brigham and Women's Hospital, Boston, MA, ¹⁶University of California, Division of Rheumatology, San Francisco, CA, ¹⁷Lupus Foundation of America, Richmond Hill, GA, ¹⁸AbbVie, Inc., Lake Bluff, IL, ¹⁹AbbVie, Inc., Libertyville, IL, ²⁰Northwell Health, Great Neck, NY, ²¹Amgen, Inc., Almada, Portugal, ²²Bristol Myers Squibb, Lawrencevile, NJ, ²³AbbVie, Inc., Worcester, MA, ²⁴Merck KGaA, Darmstadt, Germany, ²⁵UCB Pharma, Slough, United Kingdom, ²⁶AbbVie, Inc., Norristown, PA, ²⁷University of California San Diego, La Jolla, CA, ²⁸Amgen, Inc., Thousand Oaks, CA, ²⁹Biogen International GmbH, Milton, MA, ³⁰AstraZeneca, Gothenburg, Sweden, ³¹Bristol-Myers Squibb, New York, NY, ³²AstraZeneca, Cambridge, United Kingdom, ³³Genentech, San Francisco, CA, ³⁴Lupus Foundation of America, Washington, DC, ³⁵Modus Outcomes, Cambridge, MA, ³⁶Oklahoma Medical Research Foundation, Oklahoma City, OK, ³⁷UCB Pharma, Brussels, Belgium, ³⁸University of Pisa, Pisa, Italy, ³⁹Janssen, Flemington, NJ, ⁴⁰Bristol Myers Squibb, Lawrence Township, NJ, ⁴¹Centro Regional de Enfermedades Autoinmunes y Reumáticas, Rosario, Argentina, ⁴²Janssen Research & Development, San Diego, CA, ⁴³Eli Lilly, Carmel, IN, ⁴⁴Global Clinical Development, Ares Trading SA, an affiliate of Merck KGaA, Darmstadt, Germany,⁴⁵SDG LLC, West Newton, MA,⁴⁶AstraZeneca, Sollentuna, Sweden, ⁴⁷UCB Pharma, Monheim, ⁴⁸UCB Pharma, Baltimore, MD, ⁴⁹University of Occupational and Environmental Health, Kitakyusyu Fukuoka, Japan, ⁵⁰EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany, ⁵¹Amsterdam University Medical Centers, Amsterdam, Netherlands, ⁵²Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, ⁵³University of Pennsylvania and Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, ⁵⁴Janssen Research and Development, LLC, Spring House, PA, ⁵⁵Monash University, Victoria; Department of Rheumatology, Monash Health, Melbourne, Australia

Meeting: ACR Convergence 2022

Keywords: clinical trial, Measurement, Measurement Instrument, Outcome measures, Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 14, 2022

Title: SLE – Diagnosis, Manifestations, and Outcomes Poster III: Outcomes

Session Type: Poster Session D

Session Time: 1:00PM-3:00PM

Background/Purpose: Most late-phase randomised controlled trials (RCTs) of novel drugs for systemic lupus erythematosus (SLE) have failed to meet their primary endpoint or shown contradictory efficacy results(1). While many factors contribute to RCT failure, how best to measure treatment benefit remains a challenge(1). For product approval, regulators require evidence of clinical benefit, defined as a positive effect on how patients “feel, function or survive”(2). Current endpoint assessments are based on legacy disease activity measures not designed for use in RCTs or pursuant to current guidelines, and lacking patient input in their development. They are further limited by use of binary variables, glossary-defined thresholds and weighting, and inclusion of concepts not proven to reflect meaningful health aspects for SLE patients. We report the formation and initial outcomes of a global academic-industry partnership to develop a novel, patient-centred, clinician-reported outcome measure (ClinRO) for SLE RCTs: Treatment Response Measure for SLE (TRM-SLE).

Methods: A global panel of clinical-academic, metrology and regulatory experts, patient representatives and experts from 10 companies developing SLE drugs, was convened. Using consensus and participatory methods, we generated a conceptual definition for the setting, manner and purpose of TRM-SLE, with reference to regulatory guidance and using the PICO-C (Patient; Intervention; Comparator; Outcome; Context) framework. Literature review, item generation and grouping, moderated discussion and real-time voting via virtual platforms were used, with a predefined threshold of 70% agreement set to establish consensus.

Results: 45 experts from North and Latin America, Europe, and the AsiaPacific participated. 212 items were generated, including items for Patient (64), Intervention (48), Comparator (26), Outcome (50), and Context (24). Via moderated discussion and multiple rounds of voting, disagreements, which tended to be over semantic rather than definition or scope disparities, were resolved. The conceptual definition for TRM-SLE was defined with high agreement (81-100%, Table 1).

A protocol has been designed for subsequent steps that will use structured methods involving clinician researchers, industry, regulatory and metrology experts, SLE patients, and patient organisation representatives. These steps will determine the concepts of interest and measurements to be included in TRM-SLE, according to its defined context of use. Construct validity and measurement properties will be established before integration in an SLE RCT endpoint for regulatory approval worldwide.

Conclusion: A global academic-industry partnership has completed the first steps in development of an SLE ClinRO that, by design, is a measure of treatment response rather than disease activity and conforms to modern best practice and regulatory guidance.

References
1. Dolgin E. Lupus in crisis: as failures pile up, clinicians call for new tools. Nat Biotechnol. 2019;37(1):7-8.
2. Powers, J. H. et al. Clinician-Reported Outcome Assessments of Treatment Benefit: Report of the ISPOR Clinical Outcome Assessment Emerging Good Practices Task Force. Value Health 2017; 20:2–14.

Table 1: Conceptual definition for the setting, manner, & purpose of TRM-SLE and levels of consensus achieved after moderated discussion and voting

Disclosures: K. Connelly, AstraZeneca; L. Eades, None; R. Koelmeyer, None; D. Ayton, None; V. Golder, None; R. Kandane-Rathnayake, None; K. Gregory-Wong, None; H. Al-Mossawi, AstraZeneca; J. Andersen, None; C. Aranow, None; L. Arnaud, AstraZeneca, Novartis, GlaxoSmithKlein(GSK), Bristol-Myers Squibb(BMS), Bristol-Myers Squibb(BMS); A. Askanase, AstraZeneca, GlaxoSmithKlein(GSK), Aurinia, Amgen, Pfizer, Idorsia, Eli Lilly, UCB, AbbVie/Abbott, Janssen, Bristol-Myers Squibb(BMS); S. Banerjee, Bristol Myers Squibb; C. Barbey, Biogen; H. Brunner, Cincinnati Children's Hospital, Pfizer, GlaxoSmithKlein(GSK), AbbVie/Abbott, AstraZeneca, Medimmune, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb(BMS), Celgene, Eli Lilly, EMD Serono, Idorsia, Cerecor, Janssen, Roche, Merck/MSD, Novartis, R-Harm, Sanofi; J. Buie, None; L. Burke, Amgen, Novartis, Avidity, Numind, Nerre, Alelxion, PureTech; A. Cornet, None; K. Costenbader, Eli Lilly, Janssen, Amgen, AstraZeneca Pharmaceuticals LP, GlaxoSmithKline(GSK), Gilead, Exagen, Neutrolis, Cel-Sci, Alkermes; M. Dall'Era, GlaxoSmithKline (GSK), AstraZeneca, Aurinia, BMS, Amgen; K. Dantata, None; N. Delev, Bristol-Myers Squibb(BMS); A. Eldred, AbbVie/Abbott; A. Friedman, AbbVie/Abbott; R. Furie, AstraZeneca, Biogen; S. Garces, Amgen; D. Grasela, Bristol-Myers Squibb(BMS); H. Guay, AbbVie/Abbott; O. Guenther, the healthcare business of Merck KGaA, Darmstadt, Germany; M. Juarez, UCB Pharma; S. Kafka, AbbVie/Abbott; K. Kalunian, AbbVie/Abbott, Amgen, AstraZeneca, Aurinia, Biogen, Bristol Myers Squibb (BMS), Eli Lilly, Equillium, Genentech, Gilead, Janssen, Roche, Lupus Research Alliance, Pfizer, Sanford Consortium, Viela, Nektar; E. Karis, Amgen, Inc.; Y. Lahoud, Biogen; C. Lindholm, AstraZeneca; J. Lockman, Bristol-Myers Squibb(BMS); C. Lupton, AstraZeneca; J. Maller, Genentech; A. Marion, None; P. Marquis, Modus Outcomes; J. Merrill, None; T. Morel, UCB; M. Mosca, Eli Lilly, AstraZeneca, UCB, GlaxoSmithKlein(GSK); Y. Pincus, Janssen; S. Pomponi, Bristol Myers Squibb; G. Pons-Estel, Janssen, GlaxoSmithKlein(GSK), Pfizer, Werfen/Inova, Sanofi, Novartis; J. Ross Terres, Genentech; C. Sibley, Janssen; M. Silk, Eli Lilly; S. Roy, Ares Trading SA (an affiliate of Merck KGaA); L. Simon, None; A. Sorrentino, AstraZeneca, Gilead, AbbVie/Abbott; C. Stach, UCB Pharma, UCB Biosciences GmbH; G. Stojan, UCB; Y. Sun, the healthcare business of Merck KGaA, Darmstadt, Germany; Y. Tanaka, Lilly, AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Pfizer, Mitsubishi Tanabe, GlaxoSmithKline, Asahi Kasei, Takeda, Astellas, Janssen, Novartis, Sanofi, UCB, YL Biologics, MSD, Ono, Taisho Toyama, Celltrion, Gilead, Boehringer-Ingelheim, Corrona, Kowa, Amgen, AstraZeneca, AstraZeneca, Eli Lilly; E. Thomas, EMD Serono, AstraZeneca; R. van Vollenhoven, Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK), UCB, Merck/MSD, Pfizer, Roche, AbbVie, AstraZeneca, Biogen, Galapagos, Janssen, Miltenyi, R-Pharma; C. Vazquez Mateo, EMD Serono, Billerica, MA, USA; E. Vital, Sandoz, AstraZeneca, Eli Lilly, UCB, Novartis, Ostuka, Modus Therapeutics, Aurinia; V. Werth, AbbVie/Abbott, Amgen, AstraZeneca, Bristol Myers Squibb (BMS), Celgene, Eli Lilly, Genentech, GlaxoSmithKline (GSK), Janssen, Merck/MSD, Gilead, Novartis, Pfizer, Rome Pharmaceuticals, Horizon Therapeutics, Regeneron, argenx, CSL Behring, AnaptysBio, Biogen, Corbus, EMD Serono, Galderma, Nektar, Octapharma, Principia, Resolve, Sanofi, Syntimmune, Viela; E. Zollars, Amgen; Q. Zuraw, Janssen Research & Development, LLC; E. Morand, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb(BMS), Eli Lilly, Genentech, GlaxoSmithKlein(GSK), Janssen, Novartis, Servier, UCB, EMD Serono, Billerica, MA, USA.

To cite this abstract in AMA style:

Connelly K, Eades L, Koelmeyer R, Ayton D, Golder V, Kandane-Rathnayake R, Gregory-Wong K, Al-Mossawi H, Andersen J, Aranow C, Arnaud L, Askanase A, Banerjee S, Barbey C, Brunner H, Buie J, Burke L, Cornet A, Costenbader K, Dall'Era M, Dantata K, Delev N, Eldred A, Friedman A, Furie R, Garces S, Grasela D, Guay H, Guenther O, Juarez M, Kafka S, Kalunian K, Karis E, Lahoud Y, Lindholm C, Lockman J, Lupton C, Maller J, Marion A, Marquis P, Merrill J, Morel T, Mosca M, Pincus Y, Pomponi S, Pons-Estel G, Ross Terres J, Sibley C, Silk M, Roy S, Simon L, Sorrentino A, Stach C, Stojan G, Sun Y, Tanaka Y, Thomas E, van Vollenhoven R, Vazquez Mateo C, Vital E, Werth V, Zollars E, Zuraw Q, Morand E. Towards a Novel Clinician-Reported Outcome Measure for SLE – Outcomes of an International Consensus Process [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/towards-a-novel-clinician-reported-outcome-measure-for-sle-outcomes-of-an-international-consensus-process/. Accessed .

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