Data Studio: Clinical Trial Design for Glaucoma Treatment Using Humphrey Visual Field as Primary Outcome – Stanford

TITLE: Clinical Trial Design for Glaucoma Treatment Using Humphrey Visual Field as Primary OutcomeA Guide for the Statistically Perplexed
DATE: Wednesday, 4 October 2023
TIME: 3:00–4:30 PM
LOCATION: Conference Room X399, Medical School Office Building, 1265 Welch Road, Stanford, CA

INVESTIGATORS:

Laurel Stell, Biomedical Data Science
Jeffrey Goldberg, Ophthalmology
Gala Beykin, Ophthalmology

INSTRUCTORS:

Ying Lu
Chiara Sabatti
Lu Tian
Balasubramanian Narasimhan (Naras)
Brad Efron
Mei-Chiung Shih
John S. Tamaresis

WEBPAGE: https://dbds.stanford.edu/data-studio/

ABSTRACT:

The Data Studio Workshop brings together a biomedical investigator with a group of experts for an in-depth session to solicit advice about statistical and study design issues that arise while planning or conducting a research project. This week, the investigator(s) will discuss the following project with the group.

Introduction

Glaucoma treatments are typically assessed by whether they control interocular pressure (IOP), but the disease often continues to progress despite reduction in IOP. The Humphrey Visual Field (HVF) exam, which measures the retina’s sensitivity to light, is widely used to diagnose glaucoma and its progress, but its measurement error can be large in comparison to the rate of progression. Consequently, estimating the rate of decrease in HVF measurements by linear regression generally requires regular exams over 10 years or more, and even then the slope is often not statistically significant. Finally, treatments are not likely to reverse damage but only slow or delay neurodegeneration. All of these factors can result in prohibitively large sample sizes or long trial times when using HVF as primary outcome in a clinical trial.

Hypothesis & Aim

We have performed exploratory analysis of HVF exams. We hope to leverage such data to improve clinical trial inclusion criteria and statistical tests for treatment effect.

Dataset

We have HVF data from a variety of sources: (a) thirty glaucomatous eyes in a test-retest study that performed weekly exams for three months (Artes et al, 2014), (b) data from Phase 1b trials including six or fewer exams over a year or two from about 150 eyes (Goldberg et al, 2022), and (c) the public UW-HVF data set of thousands of eyes, including 450 with at least nine exams over 10 years or more–but without clinical information such as diagnosis, progression or treatment.

Statistical Models

The HVF exam measures sensitivity at an array of 52 points on the retina. We will discuss properties of the measurements at individual locations, averaged over the whole retina, and averaged over each of six regions identified by mapping neurons in the retina. We are seeking advice on statistical models for testing treatment effect.

STATISTICAL QUESTIONS: