Lead Investigator: Manju Subramanian, Boston Medical Center
Title of Proposal Research: The Impact of Race on Short Term Treatment Response to Intravitreal anti-Vascular Endothelial Growth Factor in Diabetic Macular Edema: A Pooled Analysis
Vivli Data Request: 6594
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Diabetic macular edema (DME) is the leading cause of visual loss in patients with diabetes mellitus worldwide. An estimated 3.8%, or 746,000, of the 2010 United States population is affected by diabetic macular edema. DME occurs as a complication of diabetes, where there is damage to the blood vessels in the retina resulting in leaking of fluid and the production of new, weaker blood vessels. When this occurs in the central part of the retina, or the macula, there can be severe loss in vision. It is known that patients with DME exhibit increased levels of vascular endothelial growth factor (VEGF), resulting in this abnormal retinal fluid accumulation and ultimately vision loss. Antibodies directed against VEGF injected into the eye have become the standard of care. Previous studies have reported that Black patients have a higher susceptibility for developing DME in comparison to White patients despite controlling for confounding factors such as hemoglobin A1c (an indication of the severity of diabetes) and duration of diabetes. We recently published a study demonstrating that Black patients have a significantly lower likelihood of vision improvement following anti-VEGF injections compared to White patients. Existing studies comparing the efficacy of treatment with anti-VEGF agents in DME have a predominance of White subjects and was unable to address the effects on Black patients, indicating a disparity in prevalence of disease and the population studied for treatment. We seek to expand on the results of our prior publication and analyze outcomes for participants by race and ethnicity in clinical trials from The Diabetic Retinopathy Clinical Research Network, the U.S. National Institute of Health, and several industry-sponsored studies. By analyzing this data from several clinical trials, we can perform a large-scale analysis by race and ethnicity to help understand why there are disparities faced among each group. The research will be conducted by extracting de-identified patient data from completed chart reviews and consolidating the information into a large data set—this method is known as simple pooling. Through this data, we can conduct linear and logistic multivariate regressions; this will allow us to compare a large number of variables to identify relationships between demographic, clinical, and anatomic data.
Statistical Analysis Plan:
We will combine data via simple pooling, and perform multivariate logistic and linear regression analyses using SAS v 9.4 to evaluate for statistical significance across races and ethnicities, and additionally by intravitreal agent. Regarding the search criteria for selecting a specific study, we searched ClinicalTrials.org for completed US interventional clinical trials involving diabetic macular edema that were industry-sponsored. We identified 8, and 5 of them were available through Vivli. Once the data sets are acquired, missing values for patients will be excluded. The simple pooling will be done by creating inclusion and exclusion criteria to identify patients that qualify for our analysis. We will additionally tag each patient with the original study source and will perform regression analyses to weigh potential differences between the original study samples. The tag will be added as an additional column that identifies the original study source. This will allow us to analyze the studies independently, look at different combinations of studies, and use the original study source as a control.
After consolidating data from various studies via simple pooling, we will run standard multivariate linear/logistic regression analyses using SAS v 9.4. Our team will use our original code written in C compiled on SAS using the Oracle VM Virtualbox. The code consists of several DATA steps and PROC steps to retrieve the locally stored pooled data spreadsheet and run the statistical analysis using the GLM (general linear models) procedure. Each SAS procedure includes the experimental variable, outcome variable, controls, and relevant statistical parameters. For instance, we can answer the question of whether there is a difference in treatment efficacy between two races by setting the experimental variable as the race, the outcome variable as visual acuity improvement and the controls as several variables collected in our pooled data set.
There will be agent to agent comparisons in our study. Each participant ID will have their specific treatment agent and dose listed in the pooled data sheet. The specific treatment agent will be analyzed as an independent variable as well as a control in a separate analysis when assessing the effect of other independent variables. Our analysis will be run as a linear regression, which allows us to add the agent as a nominal class variable among the controls.
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
Data Contributor: Roche
Study ID: NCT00473382
Sponsor ID: FVF4168g
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
Data Contributor: Roche
Study ID: NCT00473330
Sponsor ID: FVF4170g
Protocol T is a Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab and Ranibizumab for Diabetic Macular Edema, publicly available from DRCR.net via the Jaeb Center for Health Research. This is a randomized clinical trial that contributes to our total data size in the pooled analysis.
Data Contributor: I WILL BRING MY OWN
Study ID: DRCR Protocol T
Protocol I examines Intravitreal Ranibizumab or Triamcinolone Acetonide in Combination with Laser Photocoagulation for Diabetic Macular Edema, publicly available from DRCR.net via the Jaeb Center for Health Research. This is a randomized clinical trial that contributes to our total data size in the pooled analysis.
Data Contributor: I WILL BRING MY OWN
Study ID: Protocol I
Protocol S examines Prompt Panretinal Photocoagulation versus Intravitreal Ranibizumab with Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy, publicly available from DRCR.net via the Jaeb Center for Health Research. This is a randomized clinical trial that contributes to our total data size in the pooled analysis.
Data Contributor: I WILL BRING MY OWN
Study ID: Protocol S
Protocol H is a Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin) publicly available from DRCR.net via the Jaeb Center for Health Research. This is a randomized clinical trial that contributes to our total data size in the pooled analysis.
Data Contributor: I WILL BRING MY OWN
Study ID: Protocol H
Public Disclosures:
Nayan Sanjiv, Pawarissara Osathanugrah, Steven Ness, Xuejing Chen, Nicole Siegel, Manju L Subramanian. Impact of Race on Treatment of Ranibizumab in Diabetic Macular Edema: A Pooled Analysis. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2713.