Inborn Errors of MetabolismMetaPROMNCT04248062
Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism
An observational study of Inborn Errors of Metabolism and Urea Cycle Disorder, run by University Children's Hospital, Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Inborn Errors of Metabolism, Urea Cycle Disorder, Maple Syrup Urine Disease
- What is being tested?
- Survey
- How many people
- 69 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Aug 2019to 16 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: The included groups (experts, patients, parents/patient representatives) were all not randomly chosen. Experts are recruited based on the criteria of profession, specialization, experience and location. A sample as balanced as possible is intended. Patients and their parents are recruited based on IEM disease, disease severity, age and gender. A sample as balanced as possible is intended.
Who may be able to join
- 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
- Ability to understand German language
- Parents of a child suffering from IEM
- More than 1 year of practical experience in the field of IEM
- Ability to understand written English
- No ability to understand German language
Who cannot join
- Older than 18 years
- Severe cognitive impairment (ability to complete the Survey not existent)
- Less than 1 year of practical experience in the field of IEM
- No ability to understand written English
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification and Validation of Relevant Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism
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.
Read the detailed description
- 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).
- 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.
- Conditions
- Inborn Errors of Metabolism, Urea Cycle Disorder, Maple Syrup Urine Disease, Phenylketonurias, Methylmalonicacidemia, OTC Deficiency
- Being tested
- Survey
- Medical subject headings
- Metabolism, Inborn Errors, Urea Cycle Disorders, Inborn, Maple Syrup Urine Disease, Phenylketonurias, Methylmalonic acidemia, Ornithine Carbamoyltransferase Deficiency Disease, Amino Acid Metabolism, Inborn Errors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurveyOther
Survey: 38 preselected patient and parent reported outcomes; rating scale: 9 point likert scale (1=not at all important - 9=very important)
| Study group | Role | What they receive |
|---|---|---|
| IEM experts | Heterogeneous group of health professionals (physicians, psychologists, nutritionists) working in the field of Inborn Errors of Metabolism (IEM) Receives: Other: Survey | |
| Paediatric IEM patients | IEM patients between 10 and 18 years Receives: Other: Survey | |
| Parents of paediatric IEM patients and patient representatives | * Parents of IEM patients (between 0 and 18 years)
* Patient representatives Receives: Other: Survey |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average importance of patient reported outcomes (PRO) after first Delphi survey
Average importance-rating of the PROs in the total sample (experts, patients, parents, patient representatives); 9-point Likert scale (1 = not at all important, 2 = very important); Sum-Score for each PRO divided by number of survey-participants; Consensus about the importance of a PRO achieved if at least 70% of the voting participants from each stakeholder group scored between 7 and 9
Measured: 15 minutes (for Delphi survey 1)
Average importance of patient reported outcomes (PRO) after second Delphi survey
Average importance-rating of the PROs in the total sample (experts, patients, parents, patient representatives); 9-point Likert scale (1 = not at all important, 2 = very important); Sum-Score for each PRO divided by number of survey-participants; Consensus about the importance of a PRO achieved if at least 70% of the voting participants from each stakeholder group scored between 7 and 9
Measured: 15 minutes (for Delphi survey 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2020
- Study start1 Aug 2019
- Primary completion29 Aug 2020
- Study completion16 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Inborn Errors of MetabolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Children's Hospital, Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martina Huemer, Principal investigator, University Children's Hospital, Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04248062
- Sponsor's protocol ID
- 10650
- Acronym
- MetaPROM
- Status last verified
- Nov 2020
- First submitted
- 7 Nov 2019
- Last updated
- 4 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: In the scheduled publication, sharing of individual's voting data is not planned. The investigator's research interest refers to the average importance-voting regarding the preselected PROs.
Publications
Slade A, Isa F, Kyte D, Pankhurst T, Kerecuk L, Ferguson J, Lipkin G, Calvert M. Patient reported outcome measures in rare diseases: a narrative review. Orphanet J Rare Dis. 2018 Apr 23;13(1):61. doi: 10.1186/s13023-018-0810-x.
PubMed 29688860Morel T, Cano SJ. Measuring what matters to rare disease patients - reflections on the work by the IRDiRC taskforce on patient-centered outcome measures. Orphanet J Rare Dis. 2017 Nov 2;12(1):171. doi: 10.1186/s13023-017-0718-x.
PubMed 29096663Zeltner NA, Landolt MA, Baumgartner MR, Lageder S, Quitmann J, Sommer R, Karall D, Muhlhausen C, Schlune A, Scholl-Burgi S, Huemer M. Living with Intoxication-Type Inborn Errors of Metabolism: A Qualitative Analysis of Interviews with Paediatric Patients and Their Parents. JIMD Rep. 2017;31:1-9. doi: 10.1007/8904_2016_545. Epub 2016 Aug 13.
PubMed 26983835Weldring T, Smith SM. Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs). Health Serv Insights. 2013 Aug 4;6:61-8. doi: 10.4137/HSI.S11093. eCollection 2013.
PubMed 25114561
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification and Validation of Relevant Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism
- ClinicalTrials.gov ID
- NCT04248062
- Acronym / sponsor ID
- MetaPROM / 10650
- Conditions
- Inborn Errors of Metabolism, Urea Cycle Disorder, Maple Syrup Urine Disease, Phenylketonurias, Methylmalonicacidemia, OTC Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- University Children's Hospital, ZurichUniversity, hospital or other
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 29 Aug 2020 (actual)
- Study completion
- 16 Oct 2020 (actual)
- First posted
- 30 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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).
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IEM experts | – | Other: SurveyHeterogeneous group of health professionals (physicians, psychologists, nutritionists) working in the field of Inborn Errors of Metabolism (IEM) |
| Paediatric IEM patients | – | Other: SurveyIEM patients between 10 and 18 years |
| Parents of paediatric IEM patients and patient representatives | – | Other: Survey* Parents of IEM patients (between 0 and 18 years) * Patient representatives |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- The included groups (experts, patients, parents/patient representatives) were all not randomly chosen. Experts are recruited based on the criteria of profession, specialization, experience and location. A sample as balanced as possible is intended. Patients and their parents are recruited based on IEM disease, disease severity, age and gender. A sample as balanced as possible is intended.
Key inclusion criteria (8 listed)
- 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
- Ability to understand German language
- Parents of a child suffering from IEM
Key exclusion criteria (4 listed)
- Older than 18 years
- Severe cognitive impairment (ability to complete the Survey not existent)
- Less than 1 year of practical experience in the field of IEM
- No ability to understand written English
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SurveySurvey: 38 preselected patient and parent reported outcomes; rating scale: 9 point likert scale (1=not at all important - 9=very important) | Other | IEM experts, Paediatric IEM patients, Parents of paediatric IEM patients and patient representatives |
Primary outcome
Average importance of patient reported outcomes (PRO) after first Delphi survey
Time frame: 15 minutes (for Delphi survey 1)
Average importance-rating of the PROs in the total sample (experts, patients, parents, patient representatives); 9-point Likert scale (1 = not at all important, 2 = very important); Sum-Score for each PRO divided by number of survey-participants; Consensus about the importance of a PRO achieved if at least 70% of the voting participants from each stakeholder group scored between 7 and 9
Average importance of patient reported outcomes (PRO) after second Delphi survey
Time frame: 15 minutes (for Delphi survey 2)
Average importance-rating of the PROs in the total sample (experts, patients, parents, patient representatives); 9-point Likert scale (1 = not at all important, 2 = very important); Sum-Score for each PRO divided by number of survey-participants; Consensus about the importance of a PRO achieved if at least 70% of the voting participants from each stakeholder group scored between 7 and 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Background: PubMed 29688860Slade A, Isa F, Kyte D, Pankhurst T, Kerecuk L, Ferguson J, Lipkin G, Calvert M. Patient reported outcome measures in rare diseases: a narrative review. Orphanet J Rare Dis. 2018 Apr 23;13(1):61. doi: 10.1186/s13023-018-0810-x.
- Background: PubMed 29096663Morel T, Cano SJ. Measuring what matters to rare disease patients - reflections on the work by the IRDiRC taskforce on patient-centered outcome measures. Orphanet J Rare Dis. 2017 Nov 2;12(1):171. doi: 10.1186/s13023-017-0718-x.
- Background: PubMed 26983835Zeltner NA, Landolt MA, Baumgartner MR, Lageder S, Quitmann J, Sommer R, Karall D, Muhlhausen C, Schlune A, Scholl-Burgi S, Huemer M. Living with Intoxication-Type Inborn Errors of Metabolism: A Qualitative Analysis of Interviews with Paediatric Patients and Their Parents. JIMD Rep. 2017;31:1-9. doi: 10.1007/8904_2016_545. Epub 2016 Aug 13.
- Background: PubMed 25114561Weldring T, Smith SM. Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs). Health Serv Insights. 2013 Aug 4;6:61-8. doi: 10.4137/HSI.S11093. eCollection 2013.
- Individual participant dataSharing planned: No. In the scheduled publication, sharing of individual's voting data is not planned. The investigator's research interest refers to the average importance-voting regarding the preselected PROs.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martina Huemer principal investigator
University Children's Hospital, Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inborn Errors of Metabolism and Urea Cycle Disorder, run by University Children's Hospital, Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average importance of patient reported outcomes (PRO) after first Delphi survey (time frame: 15 minutes (for Delphi survey 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04248062, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.