Range and Heterogeneity of Outcomes in Randomized Trials of Pediatric Chronic Kidney Disease

Lauren S H Chong; Benedicte Sautenet; Allison Tong; Camilla S Hanson; Susan Samuel; Michael Zappitelli; Allison Dart; Susan Furth; Allison A Eddy; Jaap Groothoff; Nicholas J A Webb; Hui-Kim Yap; Detlef Bockenhauer; Aditi Sinha; Stephen I Alexander; Stuart L Goldstein; Debbie S Gipson; Gayathri Raman; Jonathan C Craig

doi:10.1016/j.jpeds.2017.03.034

Range and Heterogeneity of Outcomes in Randomized Trials of Pediatric Chronic Kidney Disease

J Pediatr. 2017 Jul:186:110-117.e11. doi: 10.1016/j.jpeds.2017.03.034. Epub 2017 Apr 24.

Authors

Lauren S H Chong¹, Benedicte Sautenet², Allison Tong³, Camilla S Hanson¹, Susan Samuel⁴, Michael Zappitelli⁵, Allison Dart⁶, Susan Furth⁷, Allison A Eddy⁸, Jaap Groothoff⁹, Nicholas J A Webb¹⁰, Hui-Kim Yap¹¹, Detlef Bockenhauer¹², Aditi Sinha¹³, Stephen I Alexander¹⁴, Stuart L Goldstein¹⁵, Debbie S Gipson¹⁶, Gayathri Raman¹⁷, Jonathan C Craig¹

Affiliations

¹ Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
² Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia; University Francois Rabelais, Tours, France; Department of Nephrology and Clinical Immunology, Tours Hospital, Tours, France; INSERM (U1153), Paris, France.
³ Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. Electronic address: allison.tong@sydney.edu.au.
⁴ Department of Pediatrics, Section of Nephrology, University of Calgary, Calgary, Canada.
⁵ Department of Pediatrics, Division of Pediatric Nephrology, Montreal Children's Hospital, McGill University Health Centre, McGill University, Montreal, Canada.
⁶ Department of Pediatrics and Child Health, The Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Canada.
⁷ Departments of Pediatrics and Epidemiology, Perelman School of Medicine, Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, PA.
⁸ Department of Pediatrics, University of British Columbia and the British Columbia Children's Hospital, Vancouver, Canada.
⁹ Department of Pediatric Nephrology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
¹⁰ Department of Pediatric Nephrology and National Institute for Health Research/Wellcome Trust Clinical Research Facility, University of Manchester, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Manchester, United Kingdom.
¹¹ Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
¹² University College London Centre for Nephrology, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, United Kingdom.
¹³ Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, India.
¹⁴ Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
¹⁵ Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
¹⁶ Department of Pediatrics, School of Medicine, University of Michigan, Ann Arbor, MI.
¹⁷ Sydney School of Public Health, The University of Sydney, Sydney, Australia.

PMID: 28449820
DOI: 10.1016/j.jpeds.2017.03.034

Abstract

Objective: To determine the range and heterogeneity of outcomes reported in randomized controlled trials of interventions for children with chronic kidney disease (CKD).

Study design: The Cochrane Kidney and Transplant Specialized Register was searched to March 2016. Randomized trials involving children across all stages of CKD were selected. All outcome domains and measurements were extracted from included trials. The frequency and characteristics of the outcome domains and measures were evaluated.

Results: From 205 trials included, 6158 different measurements of 100 different outcome domains were reported, with a median of 22 domains per trial (IQR 13-41). Overall, 52 domains (52%) were surrogate, 38 (38%) were clinical, and 10 (10%) were patient-reported. The 5 most commonly reported domains were blood pressure (76 [37%] trials), relapse/remission (70 [34%]), kidney function (66 [32%]), infection (61 [30%]), and height/pubertal development (51 [25%]). Mortality (14%), cardiovascular disease (4%), and quality of life (1%) were reported infrequently. The 2 most frequently reported outcomes, blood pressure and relapse/remission, had 56 and 81 different outcome measures, respectively.

Conclusions: The outcomes reported in clinical trials involving children with CKD are extremely heterogeneous and are most often surrogate outcomes, rather than clinical and patient-centered outcomes such as cardiovascular disease and quality of life. Efforts to ensure consistent reporting of outcomes that are important to patients and clinicians will improve the value of trials to guide clinical decision-making. In our study, non-English articles were excluded.

Keywords: children; chronic kidney disease; outcomes; systematic review.

MeSH terms

Adolescent
Age Factors
Blood Pressure
Child
Child, Preschool
Humans
Infant
Infant, Newborn
Kidney Function Tests
Outcome Assessment, Health Care*
Quality of Life
Randomized Controlled Trials as Topic
Recurrence
Renal Insufficiency, Chronic / therapy*
Young Adult