Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are rare conditions with pronounced variability of clinical expression. We aimed to reach consensus on the most important manifestations meriting the development of drug trials. The five-staged modified Delphi procedure consisted of two questionnaires and a consensus meeting for 40 NF experts, a survey for 63 patient representatives, and a final workshop. In the questionnaires, manifestations were scored on multiple items on a 4-point Likert scale. The highest average scores for NF experts deciding the ‘need for new treatment’ were for malignant peripheral nerve sheath tumour (MPNST) (4,0) and high grade glioma (HGG) (3,9) for NF1; meningioma (3,9) for NF2 and pain (3,9) for SWN. The patient representatives assigned high scores to all manifestations, with plexiform neurofibroma being highest in NF1 (4,0), vestibular schwannoma in NF2 (4,0), and pain in SWN (3,9). Twelve experts participated in the consensus meeting and prioritised manifestations. MPNST was ranked the highest for NF1, followed by benign peripheral nerve sheath tumours. Tumour manifestations received highest ranking in NF2, and pain was the most prominent problem for SWN. Patient representative ratings for NF1 were similar to the experts’ opinions, except that they ranked HGG as the most important manifestation. For NF2 and SWN, the patient representatives agreed with the experts. We conclude that NF experts and patient representatives consent to prioritise development of drug trials for MPNST, benign peripheral nerve sheath tumours, cutaneous manifestations and HGG for NF1; tumours for NF2; and pain for SWN.
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Acknowledgements WP7 would like to thank all NF experts who participated in the two surveys and the consensus meeting, especially CTF-Europe CCAB members and ERN-GENTURIS members. A list of participants can be found in ANNEX 9. We also express our gratitude to all the patient representatives who completed the patient representatives’ survey. We would also like to thank Claas Röhl, chairman of the NFPU, and Traceann Rose, programme director of CTF, for collaborating with us in developing and sending out the patient representatives’ survey. As a participant in the Delphi questionnaires, Dr Karajannis would like to acknowledge that his research was funded in part through the NIH/NCI Cancer Centre Support Grant P30 CA008748.
Funding This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement no. 853966. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and CTF, Global Alliance for TB Drug Development nonprofit organisation, Springworks Therapeutics Inc. DGE is supported by the National Institute for Health Research (NIHR) BRC Manchester (Grant Reference Number 1215-200074).
The authors are member of the EU Patient-centric clinical trial platform (EU-PEARL). EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 853966. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and CTF, Global Alliance for TB Drug Development non-profit organisation, Springworks Therapeutics Inc. This publication reflects the authors’ views. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein.
© 2021, The Author(s).