Dinesh Khanna1, Veronica J Berrocal1, Edward H Giannini2, James R Seibold3, Peter A Merkel4, Maureen D Mayes5, Murray Baron6, Philip J Clements7, Virginia Steen8, Shervin Assassi5, Elena Schiopu1, Kristine Phillips1, Robert W Simms9, Yannick Allanore8, Christopher P Denton10, Oliver Distler11, Sindhu R Johnson12, Marco Matucci-Cerinic13, Janet E Pope14, Susanna M Proudman15, Jeffrey Siegel16, Weng Kee Wong7, Athol U Wells17, Daniel E Furst7. 1. University of Michigan, Ann Arbor. 2. Cincinnati Children's Hospital, Cincinnati, Ohio. 3. Scleroderma Research Consultants, Litchfield, Connecticut. 4. University of Pennsylvania, Philadelphia. 5. University of Texas Health Science Center at Houston. 6. Jewish General Hospital and McGill University, Montreal, Quebec, Canada. 7. University of California, Los Angeles. 8. Paris Descartes University and Cochin Hospital, AP-HP, Paris, France. 9. Boston University, Boston, Massachusetts. 10. Royal Free and University College London Medical School, London, UK. 11. University Hospital Zurich, Zurich, Switzerland. 12. Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada. 13. Azienda Ospedaliero-Universitaria Careggi (AOUC) and University of Florence, Florence, Italy. 14. Schulich School of Medicine, Western University, London Campus, and St. Joseph's Health Care, London, Ontario, Canada. 15. Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, Australia. 16. Genentech/Roche, San Francisco, California. 17. Royal Brompton Hospital, London, UK.
Abstract
OBJECTIVE:Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs). METHODS: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT. RESULTS: Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02). CONCLUSION: We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc.
RCT Entities:
OBJECTIVE: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs). METHODS: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc. Forty scleroderma experts rated 20 patient profiles each and assessed whether each patient had improved or not improved over a period of 1 year. Using the profiles for which raters had reached a consensus on whether the patients were improved versus not improved (79% of the profiles examined), we fit logistic regression models in which the binary outcome referred to whether the patient was improved or not, and the changes in the core set items from baseline to followup were entered as covariates. We tested the final index in a previously completed RCT. RESULTS: Sixteen of 31 core items were included in the patient profiles after a consensus meeting and review of test characteristics of patient-level data. In the logistic regression model in which the included core set items were change over 1 year in the modified Rodnan skin thickness score, the forced vital capacity, the patient and physician global assessments, and the Health Assessment Questionnaire disability index, sensitivity was 0.982 (95% confidence interval 0.982-0.983) and specificity was 0.931 (95% confidence interval 0.930-0.932), and the model with these 5 items had the highest face validity. Subjects with a significant worsening of renal or cardiopulmonary involvement were classified as not improved, regardless of improvements in other core items. With use of the index, the effect of methotrexate could be differentiated from the effect of placebo in a 1-year RCT (P = 0.02). CONCLUSION: We have developed a CRISS that is appropriate for use as an outcome assessment in RCTs of early dcSSc.
Authors: P A Merkel; N P Silliman; P J Clements; C P Denton; D E Furst; M D Mayes; J E Pope; R P Polisson; J B Streisand; J R Seibold Journal: Arthritis Rheum Date: 2012-10
Authors: Lorinda Chung; Christopher P Denton; Oliver Distler; Daniel E Furst; Dinesh Khanna; Peter A Merkel Journal: Clin Exp Rheumatol Date: 2012-05-30 Impact factor: 4.473
Authors: Marius M Hoeper; Harm Jan Bogaard; Robin Condliffe; Robert Frantz; Dinesh Khanna; Marcin Kurzyna; David Langleben; Alessandra Manes; Toru Satoh; Fernando Torres; Martin R Wilkins; David B Badesch Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094
Authors: Peter A Merkel; Nancy P Silliman; Christopher P Denton; Daniel E Furst; Dinesh Khanna; Paul Emery; Vivien M Hsu; James B Streisand; Richard P Polisson; Anita Akesson; John Coppock; Frank van den Hoogen; Ariane Herrick; Maureen D Mayes; Douglas Veale; James R Seibold; Carol M Black; Joseph H Korn Journal: Arthritis Rheum Date: 2008-05-15
Authors: Alexandra B Wiese; Veronica J Berrocal; Daniel E Furst; James R Seibold; Peter A Merkel; Maureen D Mayes; Dinesh Khanna Journal: Arthritis Care Res (Hoboken) Date: 2014-11 Impact factor: 4.794
Authors: Tanja A Stamm; Malin Mattsson; Carina Mihai; Juliane Stöcker; Alexa Binder; Bettina Bauernfeind; Georg Stummvoll; Gunvor Gard; Roger Hesselstrand; Gunnel Sandqvist; Oana Draghicescu; Ana Maria Gherghe; Malina Voicu; Klaus P Machold; Oliver Distler; Josef S Smolen; Carina Boström Journal: Ann Rheum Dis Date: 2011-06 Impact factor: 19.103
Authors: Vivek Nagaraja; Marco Matucci-Cerinic; Daniel E Furst; Masataka Kuwana; Yannick Allanore; Christopher P Denton; Ganesh Raghu; Vallerie Mclaughlin; Panduranga S Rao; James R Seibold; John D Pauling; Michael L Whitfield; Dinesh Khanna Journal: Arthritis Rheumatol Date: 2020-05-18 Impact factor: 10.995
Authors: Dinesh Khanna; Cathie Spino; Sindhu Johnson; Lorinda Chung; Michael L Whitfield; Christopher P Denton; Veronica Berrocal; Jennifer Franks; Bhavan Mehta; Jerry Molitor; Virginia D Steen; Robert Lafyatis; Robert W Simms; Anna Gill; Suzanne Kafaja; Tracy M Frech; Vivien Hsu; Robyn T Domsic; Janet E Pope; Jessica K Gordon; Maureen D Mayes; Elena Schiopu; Amber Young; Nora Sandorfi; Jane Park; Faye N Hant; Elana J Bernstein; Soumya Chatterjee; Flavia V Castelino; Ali Ajam; Yue Wang; Tammara Wood; Yannick Allanore; Marco Matucci-Cerinic; Oliver Distler; Ora Singer; Erica Bush; David A Fox; Daniel E Furst Journal: Arthritis Rheumatol Date: 2019-12-10 Impact factor: 10.995
Authors: Michael B Arnold; Dinesh Khanna; Christopher P Denton; Jacob M van Laar; Tracy M Frech; Marina E Anderson; Murray Baron; Lorinda Chung; Gerhard Fierlbeck; Santhanam Lakshminarayanan; Yannick Allanore; Gabriela Riemekasten; Virginia Steen; Ulf Müller-Ladner; Helen Spotswood; Laura Burke; Jeffrey Siegel; Angelika Jahreis; Daniel E Furst; Janet E Pope Journal: Rheumatology (Oxford) Date: 2018-01-01 Impact factor: 7.580
Authors: Murray Baron; Bashar Kahaleh; Elana J Bernstein; Lorinda Chung; Philip J Clements; Christopher Denton; Robyn T Domsic; Nava Ferdowsi; Ivan Foeldvari; Tracy Frech; Jessica K Gordon; Marie Hudson; Sindhu R Johnson; Dinesh Khanna; Zsuzsannah McMahan; Peter A Merkel; Sonali Narain; Mandana Nikpour; John D Pauling; Laura Ross; Antonia Maria Valenzuela Vergara; Alessandra Vacca Journal: J Scleroderma Relat Disord Date: 2018-07-18
Authors: Dana E Orange; Jessica K Gordon; Kimberly Showalter; Robert Spiera; Cynthia Magro; Phaedra Agius; Viktor Martyanov; Jennifer M Franks; Roshan Sharma; Heather Geiger; Tammara A Wood; Yaxia Zhang; Caryn R Hale; Jackie Finik; Michael L Whitfield Journal: Ann Rheum Dis Date: 2020-10-07 Impact factor: 19.103