7234 Creation Of The Minimum Dataset Required For Monitoring The Safety And Efficacy of Growth Hormone Therapy in Children with Noonan Syndrome - A GloBE-Reg Initiative
Authors: Chen Suet Ching , Bryce Jillian , Chen Minglu , Binder Gerhard , Choong Catherine Seut , Edouard Thomas , Fu Antony , Horikawa Reiko , Hubbard Alyse , Lebl Jan , Mazzanti Laura , Romano Alicia , Guftar Shaikh M , Tamburrino Federica , Tamponi Sonia , Yger Pierre , Faisal Ahmed S , Jorge Alexander 
Published: October 2024

Disclosure: S. Chen: Research Investigator; Self; Pfizer, Inc.. J. Bryce: None. M. Chen: None. G. Binder: Advisory Board Member; Self; Ascendis, Ferring Pharmaceuticals, Ipsen, Novo Nordisk, Pfizer, Inc., Sandoz. Grant Recipient; Self; Novo Nordisk. Speaker; Self; Ferring Pharmaceuticals, Ipsen, Lilly USA, LLC, Merck, Novo Nordisk, Pfizer, Inc., Sandoz. C.S. Choong: None. T. Edouard: Advisory Board Member; Self; Biomarin, Novo Nordisk. Speaker; Self; Biomarin, Novo Nordisk. A. Fu: None. R. Horikawa: None. A. Hubbard: None. J. Lebl: Speaker; Self; Pfizer, Inc., Novo Nordisk, Merck. L. Mazzanti: Speaker; Self; Novo Nordisk, Pfizer, Inc., Sandoz. A. Romano: Consulting Fee; Self; Novo Nordisk. Speaker; Self; Novo Nordisk. M. Shaikh: Consulting Fee; Self; Novo Nordisk, Pfizer, Inc.. F. Tamburrino: None. S. Tamponi: None. P. Yger: None. S. Ahmed: Grant Recipient; Self; Novo Nordisk, Pfizer, Inc., GenSci. Speaker; Self; Ipsen. A. Jorge: Grant Recipient; Self; Biomarin. Research Investigator; Self; Novo Nordisk. Speaker; Self; Novo Nordisk, Pfizer, Inc.

Introduction: Recombinant human growth hormone (rhGH) is approved internationally for use in Noonan syndrome (NS); initially by the FDA in 2007 and most recently in Europe in 2020. Most studies have shown benefit in linear growth and adult height associated with rhGH therapy, although response to treatment often varies, and longer-term safety data is limited. Moreover, comparisons between studies are compromised by the lack of consistency in data collection. The objective of the current study was to identify the minimum dataset (MDS) that could be monitored and reported globally in a routine clinical setting. Methods: This study was undertaken by the NS Expert Working Group in GloBE-Reg, the Global Registry for Novel Therapies in Rare Bone and Endocrine Conditions (https://globe-reg.net/). Ten international clinical experts in NS from ten different countries and three patient representatives of patient organisations collaborated to develop this recommendation, based on a previously described and published methodology for the grading system to determine if an item fulfils the criteria for the MDS rhGH in childhood onset GH deficiency (GHD) (doi: 10.1159/000533763). Data fields that achieved &gt;70% consensus in terms of importance qualified for the MDS, provided &lt;50% of the group deemed the item difficult to collect. Results: Preparation for the development of the finalised MDS occurred over 4 months, including two teleconference meetings between the group members and a final consensus meeting also held virtually. A total of 256 items were compiled and 9 removed for redundancies, with 247 items subjected to the grading system. Of these, 169 items achieved at least 70% consensus as important data to collect and a total of 169, albeit different items, were deemed easy to collect when monitoring children with NS on rhGH. Combining the criteria of importance and ease of data collection, 124 fulfilled the criteria for the MDS. Six items were designated as core data, 2 were computed fields, 10 items were removed following detailed discussion and 48 items were merged, to produce the final MDS recommendation of 57 items which consisted of 20 items that were only required to be completed once, and the rest at least once annually. Importantly, the exercise also showed that the MDS for monitoring of safety and efficacy of rhGH therapy differs for the different licensed indications for rhGH use, as the need for growth hormone stimulation tests and information on reinitiation after final adult height was not included in the NS MDS in contrast to the MDS for GHD. Conclusion: In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the MDS requirement that should be collected as part of routine clinical practice, for the reporting of core outcomes that relate to safety and effectiveness of all forms of rhGH in children with NS.

Presentation: 6/3/2024