Matthew J Parkes1,2, Michael J Callaghan3,4, Leslie Tive3,4, Mark Lunt3,4, David T Felson3,4. 1. From the Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester; UK National Institute for Health Research (NIHR) Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals National Health Service (NHS) Foundation Trust, Manchester Academic Health Science Centre; Faculty of Health, Psychology, and Social Care, Department of Health Professions, Manchester Metropolitan University, Manchester, UK; Pfizer Inc., New York, New York; Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA. matthew.parkes@manchester.ac.uk. 2. M.J. Parkes, BSc (Hons), Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre; M.J. Callaghan, PhD, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, and Faculty of Health, Psychology, and Social Care, Department of Health Professions, Manchester Metropolitan University; L. Tive, PhD, Pfizer Inc.; M. Lunt, PhD, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre; D.T. Felson, MD, MPH, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, and Clinical Epidemiology Unit, Boston University School of Medicine. matthew.parkes@manchester.ac.uk. 3. From the Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester; UK National Institute for Health Research (NIHR) Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals National Health Service (NHS) Foundation Trust, Manchester Academic Health Science Centre; Faculty of Health, Psychology, and Social Care, Department of Health Professions, Manchester Metropolitan University, Manchester, UK; Pfizer Inc., New York, New York; Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA. 4. M.J. Parkes, BSc (Hons), Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre; M.J. Callaghan, PhD, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, and Faculty of Health, Psychology, and Social Care, Department of Health Professions, Manchester Metropolitan University; L. Tive, PhD, Pfizer Inc.; M. Lunt, PhD, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre; D.T. Felson, MD, MPH, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, and Clinical Epidemiology Unit, Boston University School of Medicine.
Abstract
OBJECTIVE: In rheumatoid arthritis, composite outcomes constructed from a combination of outcome measures are widely used to enhance responsiveness (sensitivity to change) and comprehensively summarize response. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain is the primary outcome measure in many osteoarthritis (OA) trials. Information from other outcomes, such as rescue medication use and other WOMAC subscales, could be added to create composite outcomes, but the sensitivity of such a composite has not been tested. METHODS: We used data from a completed trial of tanezumab for knee OA (NCT00733902). The WOMAC questionnaire and rescue medication use were measured at several timepoints, up to 16 weeks. Pain and rescue medication outcomes were standardized and combined into 3 composite outcomes through principal components analysis to produce 1 score (composite outcome) and their responsiveness was compared to WOMAC pain, the standard. We pooled all treatment doses of tanezumab into 1 treatment group, for simplicity, and compared this to the control group (placebo). RESULTS: The composite outcomes showed modestly, but not statistically significantly greater responsiveness when compared to WOMAC pain alone. Adding information on rescue medication to the composite improved responsiveness. While improvements in sensitivity were modest, the required sample sizes for trials using composites was 20-40% less than trials using WOMAC pain alone. CONCLUSION: Combining information from related but distinct outcomes considered relevant to a particular treatment improved responsiveness, could reduce sample size requirements in OA trials, and might offer a way to better detect treatment efficacy in OA trials.
OBJECTIVE: In rheumatoid arthritis, composite outcomes constructed from a combination of outcome measures are widely used to enhance responsiveness (sensitivity to change) and comprehensively summarize response. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain is the primary outcome measure in many osteoarthritis (OA) trials. Information from other outcomes, such as rescue medication use and other WOMAC subscales, could be added to create composite outcomes, but the sensitivity of such a composite has not been tested. METHODS: We used data from a completed trial of tanezumab for knee OA (NCT00733902). The WOMAC questionnaire and rescue medication use were measured at several timepoints, up to 16 weeks. Pain and rescue medication outcomes were standardized and combined into 3 composite outcomes through principal components analysis to produce 1 score (composite outcome) and their responsiveness was compared to WOMAC pain, the standard. We pooled all treatment doses of tanezumab into 1 treatment group, for simplicity, and compared this to the control group (placebo). RESULTS: The composite outcomes showed modestly, but not statistically significantly greater responsiveness when compared to WOMAC pain alone. Adding information on rescue medication to the composite improved responsiveness. While improvements in sensitivity were modest, the required sample sizes for trials using composites was 20-40% less than trials using WOMAC pain alone. CONCLUSION: Combining information from related but distinct outcomes considered relevant to a particular treatment improved responsiveness, could reduce sample size requirements in OA trials, and might offer a way to better detect treatment efficacy in OA trials.
Entities:
Keywords:
OSTEOARTHRITIS; OUTCOMES; PAIN; RESPONSIVENESS; SENSITIVITY TO CHANGE
Authors: D M van der Heijde; M A van 't Hof; P L van Riel; L A Theunisse; E W Lubberts; M A van Leeuwen; M H van Rijswijk; L B van de Putte Journal: Ann Rheum Dis Date: 1990-11 Impact factor: 19.103
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Authors: D M van der Heijde; M A van't Hof; P L van Riel; M A van Leeuwen; M H van Rijswijk; L B van de Putte Journal: Ann Rheum Dis Date: 1992-02 Impact factor: 19.103