Lead Investigator: Judith Goldstein, Johns Hopkins School of Medicine
Title of Proposal Research: National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) Calibrations for Low Vision Patients with age-related macular degeneration (AMD)
Vivli Data Request: 6007
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
It is recognized in ophthalmology that changes in visual acuity do not entirely illustrate the effects of an intervention, and with increasing options for pharmaceutical therapy in retinal disorders, an understanding of the benefits from the patient perspective must be clearly understood.
Evaluation of visual ability, the ability to perform activities that depend on vision, can be made quantitative for measuring outcomes from the patient’s perspective by employing a visual function questionnaire (VFQ). Most VFQs have a fixed set of items that describe specific vision-dependent daily activities and ask the patient to rate the difficulty of performing those activities using an ordered set of response categories. The 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), is one instrument used, however, it remains difficult to compare these findings across studies, as mean changes in raw scores are often published. The non-linearity of raw scores creates challenges to the meaningfulness of the findings, and raw scores are instrument-specific, which makes generalizing results difficult. The NEI VFQ-25, like most VFQ’s, permits opt out responses to irrelevant items (e.g., “not important”, etc.) which are scored as missing data. This reduces measurement precision, and depending on the estimation method employed, can distort the visual function measure. Rasch analysis can be employed to address both the issues of missing data and nonlinearity of raw scores. This is best achieved by calibrating tem difficulty on the NEI VFQ-25. Item calibration then positions us to employ computer adaptive testing when administering the NEI VFQ-25.
Our aim to calibrate items on the NEI VFQ-25 involves assigning a difficulty estimate to those items that have a rating scale. Our group has performed this type of analysis with the Activity Inventory VFQ using 3200 low vision patients to calibrate items. To maximize precision of item calibrations, we will want to maximize the number of patient responses to the NEI VFQ-25. Our team has collected responses to the NEI VFQ-25 from approximately 1000 patients from low vision clinics across the U.S. With additional data from Genentech studies we can improve our precision of the estimates while at the same time ensuring that the item calibrations are relevant to patients participating in retinal related clinical trials. We anticipate that this information may be of benefit to Genentech/Roche as it pursues various presentations and publications of its scientific data involving NEI VFQ-25 information, and may be of value in its indication pursuits with the EMA, FDA or other regulatory bodies that might be considering vision-related PRO’s. Once analysis is complete, our plan is to publish item calibrations in the ophthalmic literature to enhance future comparative research using publicly available NEI VFQ-25 item calibrations.
Statistical Analysis Plan:
Using the R platform and the eRm package (extended Rasch modeling), Rasch analysis will be performed on all patient responses such that maximum likelihood estimates of person parameters and item calibrations are obtained. Fit statistics and differential item function between diagnostic categories, age, and visual acuity will be assessed.
Requested Studies:
A Phase III, Double-masked, Multicenter, Randomized, Sham Injection-controlled Study of the Efficacy and Safety of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus
Sponsor: Roche
Study ID: NCT00473330
Sponsor ID: FVF4170g
A Phase III, Double-masked, Multicenter, Randomized, Sham Injection-controlled Study of the Efficacy and Safety of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus
Sponsor: Roche
Study ID: NCT00473382
Sponsor ID: FVF4168g
A Phase III, Double-masked, Multicenter, Randomized, Active Treatment-controlled Study of the Efficacy and Safety of 0.5 mg and 2.0 mg Ranibizumab Administered Monthly or on an As-needed Basis (PRN) in Patients With Subfoveal Neovascular Age-related Macular Degeneration
Sponsor: Roche
Study ID: NCT00891735
Sponsor ID: FVF4579g
A Phase III, Multicenter, Randomized, Double Masked, Sham Injection-Controlled Study of the Efficacy and Safety of rhuFab V2 (Ranibizumab) in Subjects With Minimally Classic or Occult Subfoveal Neovascular Age-Related Macular Degeneration
Sponsor: Roche
Study ID: NCT00056836
Sponsor ID: FVF2598g
A Phase IIIb, Multicenter, Randomized, Double Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects With Subfoveal Choroidal Neovascularization (CNV) With or Without Classic CNV Secondary to Age Related Macular Degeneration
Sponsor: Roche
Study ID: NCT00090623
Sponsor ID: FVF3192g
An Open-Label, Multicenter Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD) or Macular Edema Secondary to Retinal Vein Occlusion (RVO) Who Have Completed a Genentech-Sponsored Ranibizumab Study
Sponsor: Roche
Study ID: NCT00379795
Sponsor ID: FVF3426g (Cohort 1)
A Phase IIIb, Single-Masked, Multicenter, Randomized Study to Evaluate the Safety and Tolerability of Ranibizumab in Naive and Previously Treated Subjects With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)
Sponsor: Roche
Study ID: NCT00251459
Sponsor ID: FVF3689g
A Phase III, Multicenter, Randomized, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab Injection Compared With Sham in Subjects With Macular Edema Secondary to Branch Retinal Vein Occlusion
Sponsor: Roche
Study ID: NCT00486018
Sponsor ID: FVF4165g
A Phase III, Multicenter, Randomized, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab Injection Compared With Sham in Subjects With Macular Edema Secondary to Central Retinal Vein Occlusion
Sponsor: Roche
Study ID: NCT00485836
Sponsor ID: FVF4166g
A Phase III, Multicenter, Randomized, Double Masked, Active Treatment-Controlled Study of the Efficacy and Safety of rhuFab V2 (Ranibizumab) Compared With Verteporfin (Visudyne) Photodynamic Therapy in Subjects With Predominantly Classic Subfoveal Neovascular Age-Related Macular Degeneration
Sponsor: Roche
Study ID: NCT00061594
Sponsor ID: FVF2587g
A Multicenter Randomized Study Evaluating Dosing Regimens for Treatment With Intravitreal Ranibizumab Injections in Subjects With Macular Edema Following Retinal Vein Occlusion
Sponsor: Roche
Study ID: NCT01277302
Sponsor ID: FVF4967g
Public Disclosure:
Judith E. Goldstein, Chris Bradley, Alden L. Gross, Marylou Jackson, Neil Bressler, Robert W. Massof; The NEI VFQ-25C: Calibrating Items in the National Eye Institute Visual Function Questionnaire-25 to Enable Comparison of Outcome Measures. Trans. Vis. Sci. Tech. 2022;11(5):10. doi: 10.1167/tvst.11.5.10.