Michael Pugliese1, Kylie Tingley1, Andrea Chow1, Nicole Pallone2, Maureen Smith3, Pranesh Chakraborty4,5, Michael T Geraghty5, Julie K Irwin6, John J Mitchell7, Sylvia Stockler8, Stuart G Nicholls9, Martin Offringa10,11, Alvi Rahman1, Laure A Tessier4, Nancy J Butcher11,12, Ryan Iverson1, Monica Lamoureux4, Tammy J Clifford1, Brian Hutton1,9, Karen Paik1, Jessica Tao13, Becky Skidmore9, Doug Coyle1, Kathleen Duddy8, Sarah Dyack14, Cheryl R Greenberg15, Shailly Jain Ghai16, Natalya Karp17, Lawrence Korngut18, Jonathan Kronick10,11, Alex MacKenzie19, Jennifer MacKenzie20, Bruno Maranda21, Murray Potter22, Chitra Prasad16, Andreas Schulze9,23, Rebecca Sparkes18, Monica Taljaard1,7, Yannis Trakadis24, Jagdeep Walia25, Beth K Potter. 1. School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada. 2. Patient partner, Canadian Organization for Rare Disorders, Toronto, Canada. 3. Newborn Screening Ontario, Ottawa, Canada. 4. Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada. 5. Divisions of Medical Genetics and Pediatric Endocrinology, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada. 6. Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada. 7. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada. 8. Department of Pediatrics, University of Toronto, Toronto, Canada. 9. Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada. 10. Department of Psychiatry, University of Toronto, Toronto, Canada. 11. Department of Pediatrics, Dalhousie University, Halifax, Canada. 12. Patient partner, Canadian Phenylketonuria & Allied Disorders Inc, Toronto, Canada. 13. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada. 14. Department of Medical Genetics, University of Alberta, Edmonton, Canada. 15. Department of Pediatrics, Western University, London, Canada. 16. Departments of Clinical Neurosciences, University of Calgary, Calgary, Canada. 17. Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada. 18. Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada. 19. Division of Metabolics, Children's Hospital of Eastern Ontario, Ottawa, Canada. 20. Department of Pediatrics, McMaster University, Hamilton, Canada. 21. Pathology and Molecular Medicine, McMaster University, Hamilton, Canada. 22. Department of Pediatrics, Université de Sherbrooke, Sherbrooke, Canada. 23. Faculty of Medicine, University of Ottawa, Ottawa, Canada. 24. Medical Genetics, and Pediatrics, University of Calgary, Calgary, Canada. 25. Department of Human Genetics, McGill University, Montreal, Canada.
Abstract
BACKGROUND: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies. METHODS: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU. Delphi participants rated the importance of outcomes on a nine-point scale (1-3: not important, 4-6: important but not critical, 7-9: critical). Candidate outcomes were progressively narrowed down over 3 survey rounds. At the workshop, participants evaluated the remaining candidate outcomes using an adapted nominal technique, open discussion, and voting. After the workshop, we finalized the COSs and recommended measurement instruments for each outcome. RESULTS: There were 85, 61, and 53 participants across 3 Delphi rounds, respectively. The candidate core outcome lists were narrowed down to 20 outcomes per disease to be discussed at the consensus workshop. Voting by 18 workshop participants led to COSs composed of 8 and 9 outcomes for MCAD deficiency and PKU, respectively, with measurement recommendations. CONCLUSIONS: These are the first known pediatric COSs for MCAD deficiency and PKU. Adoption in future studies will help to ensure best use of limited research resources to ultimately improve care for children with these rare diseases.
BACKGROUND: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies. METHODS: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU. Delphi participants rated the importance of outcomes on a nine-point scale (1-3: not important, 4-6: important but not critical, 7-9: critical). Candidate outcomes were progressively narrowed down over 3 survey rounds. At the workshop, participants evaluated the remaining candidate outcomes using an adapted nominal technique, open discussion, and voting. After the workshop, we finalized the COSs and recommended measurement instruments for each outcome. RESULTS: There were 85, 61, and 53 participants across 3 Delphi rounds, respectively. The candidate core outcome lists were narrowed down to 20 outcomes per disease to be discussed at the consensus workshop. Voting by 18 workshop participants led to COSs composed of 8 and 9 outcomes for MCAD deficiency and PKU, respectively, with measurement recommendations. CONCLUSIONS: These are the first known pediatric COSs for MCAD deficiency and PKU. Adoption in future studies will help to ensure best use of limited research resources to ultimately improve care for children with these rare diseases.
Authors: Shelley M Vanderhout; Maureen Smith; Nicole Pallone; Kylie Tingley; Michael Pugliese; Pranesh Chakraborty; Sylvia Stockler; Martin Offringa; Nancy Butcher; Stuart G Nicholls; Beth K Potter Journal: Res Involv Engagem Date: 2021-09-14