Christian Patry1, Lukas D Sauer2, Britta Höcker3, Burkhard Tönshoff3, Anja Sander2, Kai Krupka3, Alexander Fichtner3, Jolanda Brezinski2, Yvonne Geissbühler4, Elodie Aubrun4, Anna Grinienko5, Luca Dello Strologo6, Dieter Haffner7, Jun Oh8, Ryszard Grenda9, Lars Pape10, Rezan Topaloğlu11, Lutz T Weber12, Antonia Bouts13, Jon Jin Kim14, Agnieszka Prytula15, Jens König16, Mohan Shenoy17. 1. Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany. Christian.Patry@med.uni-heidelberg.de. 2. Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany. 3. Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany. 4. Novartis Pharma AG, Basel, Switzerland. 5. Novartis Pharmaceuticals, East Hanover, NJ, USA. 6. Renal Transplant Unit, Bambino Gesù Children's Hospital, Pediatric subspecialities, Rome, Italy. 7. Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany. 8. Pediatric Nephrology, University Hospital Hamburg, Hamburg, Germany. 9. Department of Nephrology, Kidney Transplantation and Hypertension, Children's Memorial Health Institute, Warsaw, Poland. 10. Clinic for Paediatrics III, Essen University Hospital, Essen, Germany. 11. Department of Pediatric Nephrology, School of Medicine, Hacettepe University, Ankara, Turkey. 12. Pediatric Nephrology, Children's and Adolescents' Hospital, University Hospital Cologne, Medical Faculty University of Cologne, Cologne, Germany. 13. Department of Pediatric Nephrology, Amsterdam University Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands. 14. Department of Paediatric Nephrology, Nottingham University Hospital, Nottingham, UK. 15. Pediatric Nephrology and Rheumatology Department, Ghent University Hospital, Ghent, Belgium. 16. Department of General Pediatrics, University Children's Hospital, Munster, Germany. 17. Paediatric Nephrology, Royal Manchester Children's Hospital, Manchester, UK.
Abstract
BACKGROUND: Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far. METHODS: In this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554). RESULTS: Most baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m2 P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable. CONCLUSIONS: In conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.
BACKGROUND: Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far. METHODS: In this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554). RESULTS: Most baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m2 P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable. CONCLUSIONS: In conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.
Authors: R Grenda; A Watson; K Vondrak; N J A Webb; J Beattie; M Fitzpatrick; M A Saleem; R Trompeter; D V Milford; N E Moghal; D Hughes; F Perner; S Friman; R Van Damme-Lombaerts; F Janssen Journal: Am J Transplant Date: 2006-07 Impact factor: 8.086
Authors: Burkhard Tönshoff; Robert Ettenger; Luca Dello Strologo; Stephen D Marks; Lars Pape; Helio Tedesco-Silva; Anna Bjerre; Martin Christian; Matthias Meier; El-Djouher Martzloff; Barbara Rauer; Jennifer Ng; Patricia Lopez Journal: Am J Transplant Date: 2018-10-18 Impact factor: 8.086
Authors: Zhaoyi Chen; Hansi Zhang; Yi Guo; Thomas J George; Mattia Prosperi; William R Hogan; Zhe He; Elizabeth A Shenkman; Fei Wang; Jiang Bian Journal: NPJ Digit Med Date: 2021-05-14