Real-world evidence in achondroplasia: considerations for a standardized data set

Yasemin Alanay¹, Klaus Mohnike², Ola Nilsson^{3

4

5}, Inês Alves⁶, Moeenaldeen AlSayed^{7

8}, Natasha M Appelman-Dijkstra⁹, Genevieve Baujat¹⁰, Tawfeg Ben-Omran¹¹, Sandra Breyer¹², Valerie Cormier-Daire^{10

13}, Pernille Axél Gregersen¹⁴, Encarna Guillén-Navarro¹⁵, Wolfgang Högler¹⁶, Mohamad Maghnie^{17

18}, Swati Mukherjee¹⁹, Shelda Cohen¹⁹, Jeanne Pimenta¹⁹, Angelo Selicorni²⁰, J Oliver Semler^{21

22}, Sabine Sigaudy²³, Dmitry Popkov²⁴, Ian Sabir¹⁹, Susana Noval²⁵, Marco Sessa²⁶, Melita Irving²⁷

Affiliations

¹ Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Kayisdagi Cad. No:32, Atasehir, 34684, Istanbul, Turkey. yasemin.alanay@acibadem.edu.tr.
² Department of Pediatrics, Otto-von-Guericke-University, Magdeburg, Germany.
³ Division of Pediatric Endocrinology and Center for Molecular Medicine, Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
⁴ Department of Medical Sciences, Örebro University, Örebro, Sweden.
⁵ Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
⁶ ANDO Portugal, Évora, Portugal.
⁷ Department of Medical Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁸ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
⁹ Department of Internal Medicine, Division Endocrinology and Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.
¹⁰ Hôpital Necker Enfants Malades AP-HP, Paris, France.
¹¹ Genetic and Genomic Medicine Division, Sidra Medicine and Hamad Medical Corporation, Doha, Qatar.
¹² Department of Paediatrics, UKE Hamburg-Eppendorf, Hamburg, Germany.
¹³ Reference Center for Skeletal Dysplasia, Imagine Institute, Paris Cité University, Paris, France.
¹⁴ Department of Clinical Genetics and Centre for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark.
¹⁵ Medical Genetics Section, Department of Paediatrics, Virgen de la Arrixaca University Clinical Hospital, IMIB-Arrixaca, Faculty of Medicine, University of Murcia (UMU), Murcia, Spain.
¹⁶ Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria.
¹⁷ Department of Paediatrics, IRCCS Istituto Giannna Gaslini, Genoa, Italy.
¹⁸ Department of Neuroscience, Rehabilitation, Ophthalmology Genetics, Maternal and Child-Health, University of Genova, Genoa, Italy.
¹⁹ BioMarin (UK) Limited, London, UK.
²⁰ Pediatric Unit ASST Lariana, Mariani Center for Fragile Child, Como, Italy.
²¹ Faculty of Medicine, University of Cologne, Cologne, Germany.
²² Department of Pediatrics, University Hospital Cologne, Cologne, Germany.
²³ Département de Génétique Médicale, Hôpital Timone Enfant, Marseille, France.
²⁴ National Ilizarov Research Center for Traumatology and Orthopaedics, Kurgan, Russia.
²⁵ Fundación ALPE Acondroplasia, Asturias, Spain.
²⁶ Associazione per I'Informazione e lo Studio dell'Acondroplasia (AISAC), Milan, Italy.
²⁷ Guy's and St. Thomas' NHS Foundation Trust, Evelina Children's Hospital, London, UK.

PMID: 37365619
PMCID: PMC10294372
DOI: 10.1186/s13023-023-02755-w

Real-world evidence in achondroplasia: considerations for a standardized data set

Yasemin Alanay et al. Orphanet J Rare Dis. 2023.

. 2023 Jun 26;18(1):166.

doi: 10.1186/s13023-023-02755-w.

Authors

Affiliations

¹ Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Kayisdagi Cad. No:32, Atasehir, 34684, Istanbul, Turkey. yasemin.alanay@acibadem.edu.tr.
² Department of Pediatrics, Otto-von-Guericke-University, Magdeburg, Germany.
³ Division of Pediatric Endocrinology and Center for Molecular Medicine, Department of Women's and Children's Health, Karolinska Institute and University Hospital, Stockholm, Sweden.
⁴ Department of Medical Sciences, Örebro University, Örebro, Sweden.
⁵ Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
⁶ ANDO Portugal, Évora, Portugal.
⁷ Department of Medical Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁸ College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
⁹ Department of Internal Medicine, Division Endocrinology and Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.
¹⁰ Hôpital Necker Enfants Malades AP-HP, Paris, France.
¹¹ Genetic and Genomic Medicine Division, Sidra Medicine and Hamad Medical Corporation, Doha, Qatar.
¹² Department of Paediatrics, UKE Hamburg-Eppendorf, Hamburg, Germany.
¹³ Reference Center for Skeletal Dysplasia, Imagine Institute, Paris Cité University, Paris, France.
¹⁴ Department of Clinical Genetics and Centre for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark.
¹⁵ Medical Genetics Section, Department of Paediatrics, Virgen de la Arrixaca University Clinical Hospital, IMIB-Arrixaca, Faculty of Medicine, University of Murcia (UMU), Murcia, Spain.
¹⁶ Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria.
¹⁷ Department of Paediatrics, IRCCS Istituto Giannna Gaslini, Genoa, Italy.
¹⁸ Department of Neuroscience, Rehabilitation, Ophthalmology Genetics, Maternal and Child-Health, University of Genova, Genoa, Italy.
¹⁹ BioMarin (UK) Limited, London, UK.
²⁰ Pediatric Unit ASST Lariana, Mariani Center for Fragile Child, Como, Italy.
²¹ Faculty of Medicine, University of Cologne, Cologne, Germany.
²² Department of Pediatrics, University Hospital Cologne, Cologne, Germany.
²³ Département de Génétique Médicale, Hôpital Timone Enfant, Marseille, France.
²⁴ National Ilizarov Research Center for Traumatology and Orthopaedics, Kurgan, Russia.
²⁵ Fundación ALPE Acondroplasia, Asturias, Spain.
²⁶ Associazione per I'Informazione e lo Studio dell'Acondroplasia (AISAC), Milan, Italy.
²⁷ Guy's and St. Thomas' NHS Foundation Trust, Evelina Children's Hospital, London, UK.

PMID: 37365619
PMCID: PMC10294372
DOI: 10.1186/s13023-023-02755-w

Abstract

Background: Collection of real-world evidence (RWE) is important in achondroplasia. Development of a prospective, shared, international resource that follows the principles of findability, accessibility, interoperability, and reuse of digital assets, and that captures long-term, high-quality data, would improve understanding of the natural history of achondroplasia, quality of life, and related outcomes.

Methods: The Europe, Middle East, and Africa (EMEA) Achondroplasia Steering Committee comprises a multidisciplinary team of 17 clinical experts and 3 advocacy organization representatives. The committee undertook an exercise to identify essential data elements for a standardized prospective registry to study the natural history of achondroplasia and related outcomes.

Results: A range of RWE on achondroplasia is being collected at EMEA centres. Whereas commonalities exist, the data elements, methods used to collect and store them, and frequency of collection vary. The topics considered most important for collection were auxological measures, sleep studies, quality of life, and neurological manifestations. Data considered essential for a prospective registry were grouped into six categories: demographics; diagnosis and patient measurements; medical issues; investigations and surgical events; medications; and outcomes possibly associated with achondroplasia treatments.

Conclusions: Long-term, high-quality data are needed for this rare, multifaceted condition. Establishing registries that collect predefined data elements across age spans will provide contemporaneous prospective and longitudinal information and will be useful to improve clinical decision-making and management. It should be feasible to collect a minimum dataset with the flexibility to include country-specific criteria and pool data across countries to examine clinical outcomes associated with achondroplasia and different therapeutic approaches.

Keywords: Achondroplasia; Growth; Quality of life; Rare disease; Real-world data; Real-world evidence; Registry.

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Conflict of interest statement

KM received support for the present manuscript from BioMarin Pharmaceutical; had a consulting agreement with Biomarin; received payment or honoraria for lectures, podcast from Biomarin; participated on a Data Safety Monitoring Board for QED; and was Vice chair of German Patient organization BKMF e.V. ON received speakers honoraria from Pfizer, Abbott, BioMarin; participated on a Data Safety Monitoring Board or Advisory Board for BioMarin; was an XLH registry steering committee member for KyowaKirin; and was on the ESPE program organizing committee. MA received support from medical writer, funding, and article processing fees from BioMarin; consulting fees, payment or honoraria, and support for attending meetings and/or travel from BioMarin and participated on a Data Safety Monitoring Board or Advisory Board for BioMarin. NMA-D received an EU Health grant for the coordination of the European Registries for Rare Bone and Mineral Conditions. SB received support from medical writer, funding, and article processing fees from BioMarin; consulting fees, payment or honoraria, and support for attending meetings and/or travel from BioMarin and participated on a Data Safety Monitoring Board or Advisory Board for BioMarin. VC-D received payment or honoraria from BioMarin Ipsen; and participated on a Data Safety Monitoring Board or Advisory Board for ULtragenyx-Mereo, QED-Propel, BioMarin. EG-N received support for the present manuscript, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings from BioMarin Pharmaceutical; participated on a Data Safety Monitoring Board for BioMarin Pharmaceutical; and had a leadership or fiduciary role in other board, society, committee or advocacy group for AEGH. WH received consulting fees from BioMarin for an Advisory Service agreement. MM received grants or contracts from Pfizer, Novo Nordisk, Merck Serono; consulting fees and payment or honoraria from Pfizer, Novo Nordisk, Merck Serono, Sandoz, BioMarin and participated in a Data Safety Monitoring Board or Advisory Board for Pfizer. SM is an employee of BioMarin Pharmaceutical Inc. and owns stocks in the company. SC is an employee of BioMarin Europe, Ltd. and owns stock or stock options in the company. JP is an employee of BioMarin and owns stock or stock options in the company. AS received honoraria from BioMarin for participating in a Data Safety Monitoring Board. JOS received support for medical writing, funded by BioMarin; personal payment or honoraria for lectures from BioMarin. IS is an employee of BioMarin Pharmaceutical Inc. and holds stock or stock options in the company. MS received support for the present manuscript from the Associazione per l’Informazione e lo Studio Dell’Acondroplasia-ODV; two grants for members meeting from BioMarin payment or honoraria from BMRN VOXZOGO Launch Meeting 2021 and BioMarin Steering Committee Working Together with Patients; participated in the BioMarin Achondroplasia Management Guidelines and a BioMarin Advisory Board (Achondroplasia Care Pathway Survey Review); and is the unpaid president of AISAC ODV. MI received has received honoraria for consultancy services from BioMarin, QED Therapeutics, Pfizer/Therachon, Sanofi, Ascendis, Alexionk, Kyowa Kirin, Innoskel and NovoNordisk. All other authors declare that they have no competing interests.

Figures

**Fig. 1**
Data elements recommended for inclusion in prospective achondroplasia registries according to age group. *Note*: the decision to perform any investigation or document specific data is at the discretion of the treating physician, and some data elements are collected at baseline only

**Fig. 2**
Role of real-world evidence in providing insights into the natural history of achondroplasia, management of achondroplasia, and clinical outcomes associated with treatment

See this image and copyright information in PMC

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Real-world evidence in achondroplasia: considerations for a standardized data set

Affiliations

Real-world evidence in achondroplasia: considerations for a standardized data set

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources