patient and observer reported outcome measurements in inborn errors of metabolism

Conditions: Inborn Errors of Metabolism; Urea Cycle Disorder; Maple Syrup Urine Disease; Phenylketonurias; Methylmalonicacidemia; OTC Deficiency; Aminoacidopathy; Patient Reported Outcome Measurements

Summary: lnborn errors of metabolism (iem) are a heterogeneous group of rare, sometimes debilitating or even fatal diseases . in iem, both definition and assessment of meaningful outcome parameters is often extremely difficult resulting in a limited body of evidence. limited evidence results in weak recommendations which are perceived as unbinding and thus sustains heterogeneous study designs, choice of outcomes and interventions again producing non-uniform data. the goal of the current study is to identify and select reliable instruments, that measure patients' and their parents' perception about relevant (social, emotional, cognitive and physical) aspects in their lives. this set of instruments will secure the comparability of future research findings. furthermore this instruments will improve the screening of paediatric iem patients regarding their need for additional (psychosocial or consultative) support in daily hospital routine.

1. background limitations to the body of evidence on effects of interventions on important outcome parameters in iem and thus to evidence-based recommendations or guidelines are manifold. due to the rarity of each disease, knowledge about the natural history may be poor. most iem are clinically heterogeneous with severity of the disease determined by mutation type, residual enzyme activity and additional, often unidentified factors. consecutively, studies in iem are variable regarding outcome parameters, treatment regimens and targets. often the evidence on meaningful outcomes is scarce because only small subgroups of studies address them in a structured and standardized manner. in iem, there is a long-standing preference for biochemical outcome parameters, such as for example phenylalanine (phe) concentrations in phenylketonuria or total homocysteine levels in patients with remethylation disorders. however, even these at first glance objective outcome parameters have their drawbacks: phe targets differ significantly between countries and for the remethylation disorders there is no general agreement on precise target ranges for total homocysteine. due to these circumstances, studies set different targets. moreover, for same iem no meaningful biochemical parameters are even available (e.g. pompe disease). more and more patient-reported outcome measures are recognized as valid additional, complementary parameters for evaluating pharmacological, dietary or disease-management interventions in chronic diseases. proms are directly reported by the patient (and their parents). proms can be used as single measurements to assess the patient's current situation or to report changes from a previous measure (e.g. following an intervention). in contrast to the well-established parameters such as biochemical markers or disease-related mortality, proms allow direct insight into experience and performance of a patient and / or his caregivers in everyday life. furthermore, use of proms in the clinical setting improves survival rates as well as patients' satisfaction with care, disease management as well as health-related quality of life (hrqol). 2. current study in the current study the relevance of patient reported outcomes (pros) for paediatric iem patients and their families will be identified via delphi method. 35 iem experts (physicians, psychologists, nutritionists) and 30 patients and parents (anticipated 15 patients / 15 parents) will fill out a survey including potentially relevant aspects of life in paediatric iem (preselected by the interdisciplinary research team based on conducted focus groups in a previous study). participants will be asked to rate every pro regarding their relevance. a second survey, including only the important aspects (criteria based on delphi manuals), will then be completed by the participants, to reach further deduction. afterwards, a focus group with participants of the two surveys (6 metabolic experts / 3 parents / 3 patients \> 12 years) will be held at the university children's hospital in zurich, to discuss unclear ratings and additional pro suggestions. for the remaining pros, corresponding proms will be selected by the interdisciplinary research team based on the criteria of reliability, (face-, construct-) validity, quality of norm data, and frequency of usage in research.

Eligibility criteria:
\*statements above refer to iem patients included in the study inclusion criteria (patients): * suffering from rare iem (e.g. phenylketonuria, urea cycle disorders, maple syrup urine disease, methylmalonic acidemia) * ability to understand german language * cognitive ability to complete the basic survey items inclusion criteria (parents): * ability to understand german language * parents of a child suffering from iem inclusion criteria (experts): * more than 1 year of practical experience in the field of iem * ability to understand written english exclusion criteria (patients): * older than 18 years * severe cognitive impairment (ability to complete the survey not existent) inclusion criteria (parents): * no ability to understand german language exclusion criteria (experts): * less than 1 year of practical experience in the field of iem * no ability to understand written english