Identifying challenges in neurofibromatosis: a modified Delphi procedure

Abstract

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.

Fig. 1. A flowchart depicting the multiple stages of the study.

The study consisted of two pathways, one for NF experts and one for patient representatives. The expert pathway consisted of two Delphi questionnaires and a consensus meeting, the patient representatives had one survey and a consensus meeting. The final selection of manifestations was done in a final workshop. CTF Children’s Tumour Foundation, NFPU Neurofibromatosis Patients United, WP7 clinicians clinicians involved in work package 7 of the EU-PEARL project, dedicated to neurofibromatosis.

Fig. 2. Distribution of the rankings of NF1 manifestation groups as given during the expert consensus meeting and the patient representatives’ survey.

A lower ranking means higher priority for inclusion in clinical trials. Manifestation groups are sorted to the number of votes in the highest priority rankings (rank 1–3). Dotted lines: manifestation group not included in final selection.