A Community-Led Approach as a Guide to Overcome Challenges for Therapy Research in Congenital Disorders of Glycosylation
Abstract
:1. Introduction
2. Methods
2.1. Quantitative Study
2.2. Qualitative Study
3. Results
3.1. A Community-Led Mixed Methods Approach Captures the CDG Community Research Priorities, Perspectives and Experiences
3.2. Six Therapy Research Tools Are Priorities for the CDG Community
3.3. Data, Sample, and Patient Management Are the Core Elements of CDG Therapy R&D
3.3.1. CDG Biobanking (in) Success Is Defined by Sample and Data Sharing and Accessibility
Challenges of CDG Biobanks
“I feel that one of the main challenges we have is really how scattered the biobanks are (…) there’s actually lots of researcher specific biobanks. (…) in my institution we engage our patients in research and offer skin biopsies for them, and those skin biopsies are generally kept in our institution and so having those accessible to research around the world is a challenge.”(multiple roles)
Solutions for CDG Biobanks
“We don’t have many problems with parents when we say [that] we have to send blood to someone or [that] we have to send it to another country. They almost always say yes. There’s no problem to collect a little bit more of blood or even skin.”(HCP)
3.3.2. CDG Patient Registries Require Efficient Data Management
Challenges of CDG Patient Registries
Solutions for CDG Patient Registries
“(…) some sort of common language between patients and professionals”(Family member)
3.3.3. CDG Biomarker Discovery and Implementation Rely on Robust Sample and Data Collection
Challenges of CDG Biomarkers
“(…) we have been talking about good biomarkers, right? We don’t have them.”(researcher)
Solutions for CDG Biomarkers
3.3.4. CDG Disease Models Require Further Development and Use
Challenges of CDG Disease Models
“(…) when you’re trying to recapitulate the disease, the animals don’t survive. And when the animals do survive you don’t recapitulate the disease. So, that’s just a fundamental problem that we have”(industry representative)
Solutions for CDG Disease Models
“(…) the N-linked, the O-linked, the GPI [glycosylphosphatidylinositol] anchors, perhaps you can learn from one model of one disease, that can apply that to other models within that same pathway”(multiple roles)
3.3.5. Patient and Data Management Are Key Elements for Successful NHS
Challenges of CDG Natural History Studies
Solutions for CDG Natural History Studies
3.3.6. Patients and Data Realities Challenge CDG CTs
Challenges of CDG Clinical Trials
“(…) all of my patients that don’t have PMM2-CDG think PMM2-CDG is getting way too much attention (…) All CTs are for PMM2-CDG, but that doesn’t actually serve us well, because if we want to say that we’re a CDG group, then we need to be inclusive”(HCP)
Solutions for CDG Clinical Trials
“(…) grouping small groups of patients together (…) with a similar pathogenesis to PMM2”(industry representative)
3.4. Diagnosis and Therapies Are the Bidirectional Triggers of CDG Therapy Research Tool Interdependence
“(…) it’s a bit of a vicious circle, (…) we don’t have enough biomarkers to accurately diagnose, but without an accurate diagnosis families can’t get into the system, to be enrolled in the biobanks, to permit the development of biomarkers (…) it’s shortening that “diagnostic odyssey” (…) so that I as a patient can get to see you as an expert quickly, and you can take my samples and put them into the biobank, to do the research to find the biomarkers (…)”(multiple roles)
“(…) we don’t even have [CDG] newborn screening, because most clinicians think it’s not treatable (…)”(HCP)
“(…) a lot of older patients (…) can benefit from [management therapies] whereas a cure should be preferably implemented by early diagnosis”(family member)
4. Discussion
4.1. Study Limitations
- -
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- Think tanks were also exclusively conducted in English. They may have led to the underrepresentation of participants’ views with limited English proficiency while favoring native speakers expressing their opinion and sharing their insights. In order to tackle this potential limitation, command of English and other languages (according to the nationality reported in the registration form) proficiency was a weighed factor when assigning participants to the think tank groups. Additionally, during the think tank discussions, participants were stimulated to express themselves in their mother tongue when necessary, benefiting from translation into English by another discussion group member;
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- Our study may have been subject to selection bias, particularly regarding recruitment for the think tanks, which occurred in connection with the 4th World Conference on CDG. Conference participants tend to be more engaged, academically educated, and/or financially empowered participants when compared to the overall CDG community [25].
4.2. Study Strengths
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- The development and implementation of a sustained participatory, community-led study including lay and professional stakeholders from diverse backgrounds and nationalities enabled the creation of a comprehensive map of the current CDG therapeutic research landscape and the offering of orientation for future therapy R&D. Importantly, the reproducibility of this approach offers the possibility of its adaptation by other disease communities and/or for other biological questions;
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- The adoption of mixed research methods enriched the completeness and depth of the data. At the same time, it made data collection a stepwise process, guiding data analysis and strengthening study conclusions;
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- The e-survey methodology used to gather quantitative data, including survey development and dissemination, has been optimized by our research team in previous works [23,24]. Regarding the qualitative study, the key strength of the think tank methodology is based on the possibility of participants meeting face-to-face in a safe environment which stimulates sharing, reflection, and co-learning. The previous identification of the World Conference on CDG for Families and Professionals as a collaborative platform aided and added another level of innovation to the study design [25]. Framing the study around the World Conference on CDG also allowed the community to co-develop the conference agenda according to their needs and preferences. These multiple study outcomes underscore the adaptability and positive impact of people-centricity in research.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Francisco, R.; Brasil, S.; Pascoal, C.; Edmondson, A.C.; Jaeken, J.; Videira, P.A.; de Freitas, C.; Ferreira, V.d.R.; Marques-da-Silva, D. A Community-Led Approach as a Guide to Overcome Challenges for Therapy Research in Congenital Disorders of Glycosylation. Int. J. Environ. Res. Public Health 2022, 19, 6829. https://doi.org/10.3390/ijerph19116829
Francisco R, Brasil S, Pascoal C, Edmondson AC, Jaeken J, Videira PA, de Freitas C, Ferreira VdR, Marques-da-Silva D. A Community-Led Approach as a Guide to Overcome Challenges for Therapy Research in Congenital Disorders of Glycosylation. International Journal of Environmental Research and Public Health. 2022; 19(11):6829. https://doi.org/10.3390/ijerph19116829
Chicago/Turabian StyleFrancisco, Rita, Sandra Brasil, Carlota Pascoal, Andrew C. Edmondson, Jaak Jaeken, Paula A. Videira, Cláudia de Freitas, Vanessa dos Reis Ferreira, and Dorinda Marques-da-Silva. 2022. "A Community-Led Approach as a Guide to Overcome Challenges for Therapy Research in Congenital Disorders of Glycosylation" International Journal of Environmental Research and Public Health 19, no. 11: 6829. https://doi.org/10.3390/ijerph19116829