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Published in: Trials 1/2017

Open Access 01-12-2017 | Study protocol

Establishing core outcome sets for phenylketonuria (PKU) and medium-chain Acyl-CoA dehydrogenase (MCAD) deficiency in children: study protocol for systematic reviews and Delphi surveys

Authors: 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, In collaboration with the Canadian Inherited Metabolic Diseases Research Network

Published in: Trials | Issue 1/2017

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Abstract

Background

Inherited 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.

Methods

This 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.

Discussion

This 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.
Appendix
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Metadata
Title
Establishing core outcome sets for phenylketonuria (PKU) and medium-chain Acyl-CoA dehydrogenase (MCAD) deficiency in children: study protocol for systematic reviews and Delphi surveys
Authors
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
In collaboration with the Canadian Inherited Metabolic Diseases Research Network
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-2327-3

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