Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (PNs)

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Brief Title

Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (PNs)

Official Title

Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (PNs)

Brief Summary

      Background:

      People with neurofibromatosis 1 (NF1) who have plexiform neurofibromas (PNs) can have pain
      that affects their daily lives. This study aims to improve questionnaires that measure their
      pain, daily living, and physical functioning.

      Objectives:

      To examine and improve questionnaires about daily living for people with NF1 and PNs.

      Eligibility:

      People ages 5 and older with NF1 and a PN

      Design:

      Participants will be screened with medical history.

      This study will have 2 phases.

      Phase 1 participants will talk about existing pain assessment questionnaires and how PNs
      affect their life. They will have group discussions of up to 8 people of a similar age with
      NF1 and PNs, or the parents of children with it. These will last about 90 minutes. Children
      ages 5 to 7 and their parents will have one-on-one meetings instead. These will last about 45
      minutes. Discussions will be audiotaped. After the questionnaires have been changed,
      individual interviews will discuss the new wording, instructions, questions, and electronic
      format of the new forms.

      Phase 1 participants may be invited to Phase 2.

      Phase 2 participants will complete the new questionnaires. These may be pen-and-paper or
      electronic. The questionnaires will take about 30 minutes for adults and teens. Children will
      work one-on-one with a staff member and may need up to 45 minutes. A small group of
      participants will be complete the forms twice in clinic and 1 month later at home. Also, a
      small group who start a new pain treatment or have a dose increase in their treatment will
      complete the forms twice before the treatment change and 1 month later.
    

Detailed Description

      Background:

        -  Neurofibromatosis 1 (NF1) is a genetic disease with multiple clinical manifestations,
           including plexiform neurofibromas (PN) 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 PN shrinkage.

        -  A critical step toward approval of drugs to treat PNs 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 atrials, especially for assessing
           changes in symptoms, such as pain.

        -  Currently, no valid PRO measures exist that are specific to the NF1 population to assess
           PN pain, its functional impact on an individual s life, or overall physical functioning,
           which may be affected by PNs.

      Objectives:

        -  Phase 1: Qualitative Evaluation

           ---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, PNs and pain to use as endpoints in clinical trials for
           individuals with NF1 and PNs.

        -  Phase 2: Evaluation of Psychometric Properties and Collection of Normative Data

             -  To evaluate final versions of the NRS-11, PII, and PROMIS-PF measures on
                reliability, validity, sensitivity to change, and feasibility in individuals with
                NF1 and PNs.

      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 (PN) that is at least >3cm on physical exam or >3mL on volumetric MRI. Patients
      must be at least 5 years of age and able to understand and speak English.

      Design:

      This protocol will be a limited site, multi-institutional research study to maximize our
      ability to assess a large, diverse sample of individuals with NF1. NCI is the lead
      institution and the three participating sites are Children s National Medical Center,
      University of Chicago, and Cincinnati Children s Hospital.

      This study will consist of 2 phases:

        -  Phase 1: Qualitative Evaluation

           --The first phase involves evaluation of current modifications and the need for any
           additional modification of the NRS-11 and the PII and evaluating the most appropriate
           items from the PROMIS-PF item bank to use in the PROMIS-PF short form by conducting
           focus groups and interviews with patients diagnosed with NF1 and PNs and parents of
           children. We will conduct up to 24 focus groups across various age bands. We will
           conduct up to four groups of 6-8 subjects for each age band (8-11 years; 12-14 years;
           15-19 years [still in high school]; 18- 24 years [graduated from high school]; 25+
           years; and parents of children with NF1). In lieu of focus groups with young children
           (ages 5-7), we will conduct individual cognitive interviews. We will conduct up to 6
           interviews for children ages 5, 6, and 7, resulting in up to 18 child cognitive
           interviews; we will additionally conduct up to 6 cognitive interviews with parents of
           children 5-7. This qualitative data will be evaluated and any necessary changes based on
           patient responses, will be made to the NRS-11, PII, and PROMIS-PF. The measures will
           then be converted into an electronic format that will have the same items and will have
           the same question and answer format as the paper questionnaires. It will be administered
           on an electronic tablet. We will then conduct up to 32 cognitive interviews across 3
           broad age bands (8-12, 13-19, and 18+) up to 10 cognitive interviews with parents, and
           up to 20 additional interviews across age bands if deemed necessary following
           qualitative analysis for a maximum ceiling of 62 patients with a target of 42 cognitive
           interviews to evaluate the measures. Based on these qualitative results these versions
           will be updated if necessary to prepare for phase 2.

        -  Phase 2: Evaluation of Psychometric Properties and Collection of Normative Data

             -  The second phase will evaluate the final electronic versions of the NRS-11, the
                PII, and the PROMIS-PF using a cross-sectional design to examine internal
                consistency, construct validity, sensitivity to change, and to provide normative
                data on the study measures for the NF1 population. It is our goal to recruit from
                14 to 16 patients, with a target of 15 in each of 8 phase 2 age bands for an
                approximate ceiling of 128 (target = 120) patients, 64 parents of children (target
                = 60) 8+ and 16 parents of children ages 5-7 (target = 15). All patients and
                parents will be asked to complete the measures two different times to examine
                test-retest reliability or sensitivity to change. For the sensitivity to change
                analysis, a subset of patients will be given the measure before and after starting
                a new pain medication treatment (including new prescriptions and dose escalations)
                or starting a new drug to reduce tumor size.
    


Study Type

Observational


Primary Outcome

Feasability

Secondary Outcome

 Convert the measures into electronic format

Condition

Neurofibromatosis 1


Study Arms / Comparison Groups

 1/Phase 1 Focus Group
Description:  Patients with NF1 who have PNs and report experiencing PN related pain and parents ofthese patients. (completed)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

486

Start Date

November 13, 2015

Completion Date

February 28, 2023

Primary Completion Date

February 28, 2023

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  Documented NF1 either by NIH clinical criteria or molecularly-proven mutation in the
             NF1 gene AND Greater than or equal to 1 plexiform neurofibroma in any location that is
             either symptomatic or asymptomatic, and is defined by the following:

               1. a neurofibroma that has grown along the length of a nerve and may involve
                  multiple fascicles and branches OR a spinal neurofibroma that involves two or
                  more levels with connection between the levels or extending laterally along the
                  nerve OR a skin thickness neurofibroma;

               2. measures greater than or equal to 3cm on longest diameter by visual exam,
                  palpation or 2D MR imaging OR greater than or equal to 3mL by volumetric MR
                  imaging.

          -  Age greater than or equal to 5 years.

          -  Ability of subject or parent or guardian to understand and the willingness to sign a
             written informed consent document.

          -  Participants must be able to understand and speak the English language.

          -  For phase 1 focus groups only, patients need to report experiencing PN related pain
             recently with a minimum pain level of 3 on the current NRS-11 or report taking
             prescription medication that reduces pain and experiencing PN related pain recently
             with a minimum pain level of 1 on the current NRS-11.

          -  For phase 2, participants in the group evaluating sensitivity to change will need to
             be starting a new pain medication regimen or increasing the dose of their existing
             pain medication, or starting a drug to reduce PN size.

          -  Parent or Guardian Inclusion Criteria

          -  Parent or Guardian of participating subject

          -  Participants must be able to understand and speak the English language

        EXCLUSION CRITERIA:

          -  Patients with severe cognitive or behavior impairments who, in the judgment of the
             investigators, would not be able to cooperate with the study procedures will be
             excluded.

          -  For phase 2, patients participating in the test-retest subgroup cannot be enrolled on
             a clinical trial or cannot have started a new pain treatment regimen at their
             appointment (e.g., medication, therapy, physical therapy, etc.)
      

Gender

All

Ages

5 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Pamela L Wolters, Ph.D., (240) 760-6035, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02544022

Organization ID

150195

Secondary IDs

15-C-0195

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Pamela L Wolters, Ph.D., Principal Investigator, National Cancer Institute (NCI)


Verification Date

August 31, 2021