• Beth K Potter, Brian Hutton, Tammy J Clifford, Nicole Pallone, Maureen Smith, Sylvia Stockler, Pranesh Chakraborty, Pauline Barbeau, Chantelle M Garritty, Michael Pugliese, Alvi Rahman, Becky Skidmore, Laure Tessier, Kylie Tingley, Doug Coyle, Cheryl R Greenberg, Lawrence Korngut, Alex MacKenzie, John J Mitchell, Stuart Nicholls, Martin Offringa, Andreas Schulze, Monica Taljaard, and Canadian Inherited Metabolic Diseases Research Network.
• School of Epidemiology and Public Health, University of Ottawa, 600 Peter Morand Drive, Ottawa, ON, K1G 5Z3, Canada. bpotter@uottawa.ca.
• Trials. 2017 Dec 19; 18 (1): 603.

BackgroundInherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. There are important evidence gaps related to the comparative effectiveness of therapies for IMD, which are in part due to challenges in conducting randomized controlled trials (RCTs) for rare diseases. Registry-based RCTs present a unique opportunity to address these challenges provided the registries implement standardized collection of outcomes that are important to patients and their caregivers and to clinical providers and healthcare systems. Currently there is no core outcome set (COS) for studies evaluating interventions for paediatric IMD. This protocol outlines a study that will establish COS for each of two relatively common IMD in children, phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.MethodsThis two-part study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Part 1 includes a rapid review and development of an evidence map to identify a comprehensive listing of outcomes reported in past studies of PKU and MCAD deficiency. The review follows established methods for knowledge synthesis, including a comprehensive search strategy, two stages of screening citations against inclusion/exclusion criteria by two reviewers working independently, and extraction of important data elements from eligible studies, including details of the outcomes collected and outcome measurement instruments. The review findings will inform part 2 of our study, a set of Delphi surveys to establish consensus on the highest priority outcomes for each condition. Healthcare providers, families of children with PKU or MCAD deficiency, and health system decision-makers will be invited to participate in two to three rounds of Delphi surveys. The design of the surveys will involve parents of children with IMD who are part of a family advisory forum.DiscussionThis protocol is a crucial step in developing the capacity to launch RCTs with meaningful outcomes that address comparative effectiveness questions in the field of paediatric IMD. Such trials will contribute high-quality evidence to inform decision-making by patients and their family members, clinicians, and policy-makers.

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