Bénédicte Sautenet1, Allison Tong2, Gabrielle Williams2, Brenda R Hemmelgarn3, Braden Manns3, David C Wheeler4, Peter Tugwell5, Wim van Biesen6, Wolfgang C Winkelmayer7, Sally Crowe8, Tess Harris9, Nicole Evangelidis2, Carmel M Hawley10, Carol Pollock11, David W Johnson10, Kevan R Polkinghorne12, Kirsten Howard13, Martin P Gallagher14, Peter G Kerr12, Stephen P McDonald15, Angela Ju2, Jonathan C Craig2. 1. Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Sydney, Australia; University Francois Rabelais, Tours, France; Department of Nephrology and Clinical Immunology, Tours Hospital, Tours, France; INSERM, U1246, Tours, France. Electronic address: benedicte.sautenet@univ-tours.fr. 2. Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Sydney, Australia. 3. Department of Medicine, University of Calgary, Calgary, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Canada; Libin Cardiovascular Institute, University of Calgary, Calgary, Canada; O'Brien Institute of Public Health, University of Calgary, Calgary, Canada; University of Calgary, Calgary, Canada. 4. Centre for Nephrology, University College London, London, United Kingdom. 5. Department of Medicine, University of Ottawa, Ottawa, Canada. 6. Renal Division, Ghent University Hospital, Ghent, Belgium. 7. Selzman Institute for Kidney Health, Section of Nephrology, Baylor College of Medicine, Houston, TX. 8. Crowe Associates, Oxon, United Kingdom. 9. PKD International, Geneva, Switzerland. 10. Queensland School of Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia; Translational Research Institute, Brisbane, Australia; Metro South and Ipswich Nephrology and Transplant Services (MINTS), Brisbane, Australia. 11. Renal Division, Kolling Institute, Sydney, New South Wales, Australia. 12. Monash Medical Centre and Monash University, Clayton, Australia; Department of Epidemiology & Preventative Medicine, Monash University, Clayton, Australia. 13. Sydney School of Public Health, The University of Sydney, Sydney, Australia. 14. Concord Clinical School, The University of Sydney, Sydney, Australia. 15. Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, Australia; Faculty of Health Science, University of Adelaide, Adelaide, Australia.
Abstract
BACKGROUND: Clinical trials are most informative for evidence-based decision making when they consistently measure and report outcomes of relevance to stakeholders. We aimed to assess the scope and consistency of outcomes reported in trials for hemodialysis. STUDY DESIGN: Systematic review. SETTING & POPULATION: Adults requiring maintenance hemodialysis enrolled in clinical trials. SELECTION CRITERIA: All Cochrane systematic reviews of interventions published by August 29, 2016, and the trials published and registered in ClinicalTrials.gov since January 2011. INTERVENTIONS: Any hemodialysis-related interventions. OUTCOMES: Frequency and characteristics of the reported outcome domains and measures. RESULTS: From the 362 trials, we extracted and classified 10,713 outcome measures (a median of 21 [IQR, 10-39] per trial) into 81 different outcome domains, of which 42 (52%) were surrogate; 25 (31%), clinical; and 14 (17%), patient reported. The number of outcome measures reported significantly changed over time. The 5 most commonly reported domains were all surrogates: phosphate (125 [35%] trials), dialysis adequacy (120 [33%]), anemia (115 [32%]), inflammatory markers (114 [31%]), and calcium (109 [30%]). Mortality, cardiovascular diseases, and quality of life were reported very infrequently (73 [20%], 44 [12%], and 32 [9%], respectively). LIMITATIONS: For feasibility, we included a sampling frame that included only trials identified in Cochrane systematic reviews or ClinicalTrials.gov. CONCLUSIONS: Outcomes reported in clinical trials involving adults receiving hemodialysis are focused on surrogate outcomes, rather than clinical and patient-centered outcomes. There is also extreme multiplicity and heterogeneity at every level: domain, measure, metric, and time point. Estimates of the comparative effectiveness of available interventions are unreliable and improvements over time have been inconsistent.
BACKGROUND: Clinical trials are most informative for evidence-based decision making when they consistently measure and report outcomes of relevance to stakeholders. We aimed to assess the scope and consistency of outcomes reported in trials for hemodialysis. STUDY DESIGN: Systematic review. SETTING & POPULATION: Adults requiring maintenance hemodialysis enrolled in clinical trials. SELECTION CRITERIA: All Cochrane systematic reviews of interventions published by August 29, 2016, and the trials published and registered in ClinicalTrials.gov since January 2011. INTERVENTIONS: Any hemodialysis-related interventions. OUTCOMES: Frequency and characteristics of the reported outcome domains and measures. RESULTS: From the 362 trials, we extracted and classified 10,713 outcome measures (a median of 21 [IQR, 10-39] per trial) into 81 different outcome domains, of which 42 (52%) were surrogate; 25 (31%), clinical; and 14 (17%), patient reported. The number of outcome measures reported significantly changed over time. The 5 most commonly reported domains were all surrogates: phosphate (125 [35%] trials), dialysis adequacy (120 [33%]), anemia (115 [32%]), inflammatory markers (114 [31%]), and calcium (109 [30%]). Mortality, cardiovascular diseases, and quality of life were reported very infrequently (73 [20%], 44 [12%], and 32 [9%], respectively). LIMITATIONS: For feasibility, we included a sampling frame that included only trials identified in Cochrane systematic reviews or ClinicalTrials.gov. CONCLUSIONS: Outcomes reported in clinical trials involving adults receiving hemodialysis are focused on surrogate outcomes, rather than clinical and patient-centered outcomes. There is also extreme multiplicity and heterogeneity at every level: domain, measure, metric, and time point. Estimates of the comparative effectiveness of available interventions are unreliable and improvements over time have been inconsistent.
Authors: Simon A Carter; Talia Gutman; Charlotte Logeman; Dan Cattran; Liz Lightstone; Arvind Bagga; Sean J Barbour; Jonathan Barratt; John Boletis; Dawn Caster; Rosanna Coppo; Fernando C Fervenza; Jürgen Floege; Michelle Hladunewich; Jonathan J Hogan; A Richard Kitching; Richard A Lafayette; Ana Malvar; Jai Radhakrishnan; Brad H Rovin; Nicole Scholes-Robertson; Hérnan Trimarchi; Hong Zhang; Karolis Azukaitis; Yeoungjee Cho; Andrea K Viecelli; Louese Dunn; David Harris; David W Johnson; Peter G Kerr; Paul Laboi; Jessica Ryan; Jenny I Shen; Lorena Ruiz; Angela Yee-Moon Wang; Achilles Hoi Kan Lee; Samuel Fung; Matthew Ka-Hang Tong; Armando Teixeira-Pinto; Martin Wilkie; Stephen I Alexander; Jonathan C Craig; Allison Tong Journal: Clin J Am Soc Nephrol Date: 2020-04-30 Impact factor: 8.237
Authors: Karine E Manera; David W Johnson; Jonathan C Craig; Jenny I Shen; Lorena Ruiz; Angela Yee-Moon Wang; Terence Yip; Samuel K S Fung; Matthew Tong; Achilles Lee; Yeoungjee Cho; Andrea K Viecelli; Benedicte Sautenet; Armando Teixeira-Pinto; Edwina Anne Brown; Gillian Brunier; Jie Dong; Tony Dunning; Rajnish Mehrotra; Saraladevi Naicker; Roberto Pecoits-Filho; Jeffrey Perl; Martin Wilkie; Allison Tong Journal: Clin J Am Soc Nephrol Date: 2018-12-20 Impact factor: 8.237
Authors: Karine E Manera; Allison Tong; Jonathan C Craig; Jenny Shen; Shilpa Jesudason; Yeoungjee Cho; Benedicte Sautenet; Armando Teixeira-Pinto; Martin Howell; Angela Yee-Moon Wang; Edwina A Brown; Gillian Brunier; Jeffrey Perl; Jie Dong; Martin Wilkie; Rajnish Mehrotra; Roberto Pecoits-Filho; Saraladevi Naicker; Tony Dunning; Nicole Scholes-Robertson; David W Johnson Journal: Kidney Int Date: 2019-03-29 Impact factor: 10.612
Authors: Simon A Carter; Liz Lightstone; Dan Cattran; Allison Tong; Arvind Bagga; Sean J Barbour; Jonathan Barratt; John Boletis; Dawn J Caster; Rosanna Coppo; Fernando C Fervenza; Jürgen Floege; Michelle A Hladunewich; Jonathan J Hogan; A Richard Kitching; Richard A Lafayette; Ana Malvar; Jai Radhakrishnan; Brad H Rovin; Nicole Scholes-Robertson; Hernán Trimarchi; Hong Zhang; Samaya Anumudu; Yeoungjee Cho; Talia Gutman; Emma O'Lone; Andrea K Viecelli; Eric Au; Karolis Azukaitis; Amanda Baumgart; Amelie Bernier-Jean; Louese Dunn; Martin Howell; Angela Ju; Charlotte Logeman; Melissa Nataatmadja; Benedicte Sautenet; Ankit Sharma; Jonathan C Craig Journal: Clin J Am Soc Nephrol Date: 2021-12-30 Impact factor: 8.237
Authors: Allison Tong; Nicole Scholes-Robertson; Carmel Hawley; Andrea K Viecelli; Simon A Carter; Adeera Levin; Brenda R Hemmelgarn; Tess Harris; Jonathan C Craig Journal: Nat Rev Nephrol Date: 2022-06-06 Impact factor: 42.439
Authors: Allison Tong; Braden Manns; Angela Yee Moon Wang; Brenda Hemmelgarn; David C Wheeler; John Gill; Peter Tugwell; Robert Pecoits-Filho; Sally Crowe; Tess Harris; Wim Van Biesen; Wolfgang C Winkelmayer; Adeera Levin; Aliza Thompson; Vlado Perkovic; Angela Ju; Talia Gutman; Amelie Bernier-Jean; Andrea K Viecelli; Emma O'Lone; Jenny Shen; Michelle A Josephson; Yeoungjee Cho; David W Johnson; Bénédicte Sautenet; Marcello Tonelli; Jonathan C Craig Journal: Kidney Int Date: 2018-10-22 Impact factor: 10.612
Authors: Aminu K Bello; Ikechi G Okpechi; Mohamed A Osman; Yeoungjee Cho; Htay Htay; Vivekanand Jha; Marina Wainstein; David W Johnson Journal: Nat Rev Nephrol Date: 2022-02-22 Impact factor: 42.439
Authors: Sara S Jdiaa; Nedaa M Husainat; Razan Mansour; Mohamad A Kalot; Kerri McGreal; Fouad T Chebib; Ronald D Perrone; Alan Yu; Reem A Mustafa Journal: Kidney Int Rep Date: 2022-07-05
Authors: Emily Duncanson; Paul N Bennett; Andrea Viecelli; Kathryn Dansie; William Handke; Allison Tong; Suetonia Palmer; Shilpanjali Jesudason; Stephen P McDonald; Rachael L Morton Journal: BMJ Open Date: 2020-11-06 Impact factor: 2.692