Abstract
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.
Highlights
Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life
Potter et al Trials (2017) 18:603 (Continued from previous page). This protocol is a crucial step in developing the capacity to launch randomized controlled trials (RCTs) with meaningful outcomes that address comparative effectiveness questions in the field of paediatric IMD
Rapid review and evidence map The rapid review and evidence map will address the following primary research question: “What outcomes are reported in key publications related to children diagnosed with phenylketonuria and medium-chain acylCoA dehydrogenase deficiency?” A secondary research question is “Among key publications as described above, what outcome measurement instruments are described or used to collect data for these outcomes?” The review will build on Canadian Inherited Metabolic Diseases Research Network (CIMDRN)’s previous work, including a scoping review of patient/parent-reported outcomes in chronic paediatric illness [66] and qualitative studies of patient/family priorities [6, 66]
Summary
Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. With promising new interventions for IMD (including drug, dietary, stem cell, and surgical therapies) rapidly emerging [9], it is vital that their efficacy be evaluated in explanatory studies within controlled settings and that their effectiveness comparative to current standard treatment be assessed in pragmatic studies within real-world settings [8, 10, 11] Such evaluations should be based upon outcomes of greatest clinical importance and of importance to patients and their family members and should capture measures of cost and health system impact [11, 12]. The careful consideration of these different perspectives is critical when studying treatments for rare diseases, including IMD, since the relative benefits and harms of alternative therapies may differ depending on which outcomes are studied from across Berwick and colleagues’ ‘triple aim’ (i.e., medically-defined outcomes, patient experiences and quality of life, and health system impacts) [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
