US Food and Drug Administration Analysis of Patient-Reported Diarrhea and Its Impact on Function and Quality of Life in Patients Receiving Treatment for Breast Cancer |
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| Institution: | 1. ORISE, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA;2. Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD, USA;3. Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA;1. Health Economic Assessment Network, Paris, France;2. French National Center for Scientific Research, Paris, France;3. Sciences Po, Center of the Sociology of Organizations, Paris, France;4. Sociology and Anthropology Department, Paris 8 University, Paris, France;5. Rhumatology Department, Cochin Hospital, Paris, France;6. French League Against Rheumatism (AFLAR), Paris, France;7. UCB Pharma, Colombes, France;8. Rhumatology Department, Grenobles Alpes University Hospital, Echirolles, France;9. Kantar Health, Gentilly, France;1. Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC, USA;2. Department of Veterans Affairs, Durham VA Medical Center, Durham, NC, USA;3. Duke University Medical Center, Durham, NC, USA;4. Department of Veterans Affairs, VA Boston Healthcare System, Boston, MA, USA;5. Duke Cancer Institute, Durham, NC, USA;6. Duke Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA;7. Section of Hematology/Oncology, Raymond G. Murphy New Mexico Veterans Affairs Medical Center, Albuquerque, NM, USA;8. Division of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;9. Department of Veterans Affairs, National Oncology Program, Durham, NC, USA;1. Univ Lyon, Université Lumière Lyon 2, GATE UMR 5824, Ecully, France;2. Centre d’Etudes et de Recherches Interdisciplinaires sur la Sécurité Civile, Aix-en-Provence, France;1. School of Population Health, Curtin University, Perth, Australia;2. Department of Community Medicine, University of Tromsø, Tromsø, Norway;3. Division of Health Services, Norwegian Institute of Public Health, Oslo, Norway;1. Exeter Test Group, University of Exeter Medical School, St Luke’s Campus, Exeter, England, UK;2. Health Economics Group, University of Exeter Medical School, St Luke’s Campus, Exeter, England, UK;3. PenTAG, University of Exeter Medical School, St Luke’s Campus, Exeter, England, UK;4. University of Exeter, Exeter, England, UK;1. Centre for Health Economics, Monash University, Melbourne, Australia;2. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia;3. Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia;4. Department of Cardiothoracic Surgery, Monash Health, Monash University, Melbourne, Australia;5. Department of Haematology, Monash Health, Monash University, Melbourne, Australia;6. School of Public Health, Curtin University, Perth, Australia |
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| Abstract: | ObjectivesMany trials conclude “no clinically meaningful detriment” to health-related quality of life (HRQL) or function between arms, even when notable differential toxicity is observed. Mean change from baseline analyses of function or HRQL can possibly obscure important change in subgroups experiencing symptomatic toxicity. We evaluate the impact of diarrhea, a key treatment arm toxicity, on patient-reported HRQL and functioning in clinical trials submitted to US Food and Drug Administration.MethodsThis study used 4 randomized, breast cancer trials (adjuvant to late-line metastatic) as case examples. Diarrhea, physical functioning (PF), and global health status and quality of life (GHS/QoL) from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 were analyzed at baseline and approximately 3 and 6 months.ResultsGenerally, patients reporting very much diarrhea at months 3 and 6 had worse PF (9-19 points lower) and GHS/QoL (16-19 points lower) than patients reporting no diarrhea regardless of treatment arm. In the change from baseline analysis, patients reporting very much diarrhea also experienced a greater decrease in PF (6-13 points) and GHS/QoL (6-16 points) versus patients reporting no diarrhea in both arms.ConclusionsIn trials with moderate to large differences in symptomatic toxicity by arm, reporting “no meaningful difference in functioning and HRQL between arms” based on mean change from baseline analysis is insufficient and may obscure important impacts on subgroups experiencing symptomatic adverse events. Additional exploratory analyses with simple data visualizations evaluating functioning or HRQL in patient subgroups experiencing expected symptomatic toxicities can further inform the safety and tolerability of an investigational agent. |
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| Keywords: | diarrhea health-related quality of life patient-reported outcome physical functioning tolerability |
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