Background:
- Neurofibromatosis 1 (NF1) is a genetic disease with multiple clinical
manifestations, including plexiform neurofibromas (pNFs) that can cause pain and may
significantly impact daily functioning and quality of life (QOL).
- Patient-reported outcomes (PROs) are useful in trials for conditions that are
disabling and chronic like NF1, where symptom reduction and improved functioning and
QOL currently are important treatment outcomes, which may occur with pNF shrinkage.
- A critical step toward approval of drugs to treat pNFs is to evaluate clinical
benefit in conjunction with a reduction in tumor volume as assessed by imaging
endpoints.
- The FDA requests the use of PROs in NF1 clinical trials, especially for assessing
changes in symptoms, such as pain.
- Currently, no valid PRO measures exist that are specific to the NF1 population to
assess pNF pain or its functional impact on an individual s life.
Objectives:
- Phase 1: Qualitative Evaluation - COMPLETE
--To evaluate current modifications and the need for any additional modifications to
existing measures of pain intensity (Numeric Rating Scale; NRS-11) and pain
interference (Pain Interference Index; PII) and select the most appropriate items to
measure physical functioning (PROMIS Physical Functioning; PROMIS-PF) in NF1 based
on qualitative feedback from patients with NF1, pNFs and pain to use as endpoints in
clinical trials for individuals with NF1 and pNFs.
- Phase 2: Evaluation of Psychometric Properties and Collection of Normative Data
- To evaluate final versions of the NRS-11 (now called the PAin INtensity Scale for
pNF [PAINS-pNF]) and PII (now called the Pain Interference Index for pNF [PIIpNF])
measures on reliability, validity, and feasibility in individuals with NF1 and pNFs.
Eligibility:
- Patients with documented NF1 either by NIH clinical criteria or molecularly-proven
mutation in the NF1 gene will be included in the study. Patients must have at least
1 plexiform neurofibroma (pNF) that is at least 3cm on longest diameter by physical
exam (i.e. visual exam, palpation) or 2D MR imaging OR >=3mL by volumetric MR
imaging. Patients must be at least 8 years of age and able to understand, read, and
speak English.
- Patients will be ineligible if they were enrolled on a MEK inhibitor trial in the
past 12 months or began a new pain treatment regimen (e.g., medication, psychosocial
therapy, physical therapy, etc.) within the past three months at the time of
recruitment.
- Primary caregivers (i.e. parent, guardian, grandparent) of participants younger than
18 years old are also eligible to participate in order to provide parent report
information to further validate the PII-pNF questionnaire for parents.
Design:
- This protocol will be a multi-institutional research study to maximize our ability
to assess a large, diverse sample of individuals with NF1.
- This study will consist of 2 phases. During the first phase, we conducted the
qualitative portion of the study with individuals with NF1, ages >=5 years, most
with pNF-related pain, using both focus groups and individual interviews. During
Phase 2, we will evaluate the final electronic versions of the PAINS-pNF and the
PII-pNF using a microlongitudinal design to examine internal consistency, construct
validity, and test-retest reliability, and to provide normative data on the study
measures for the NF1 population.
- Our goal for phase 2 is to recruit between 14 to 16 patients, with a target of 15 in
each of the eight phase 2 age bands for an approximate ceiling of 128 patients >=8
years old (target = 120) and 48 parents of children 8-17 years old (target = 45).
All patients and parents will be asked to complete the measures two weeks in a row
to examine test-retest reliability.
