Characteristics of Design and Statistical Analysis of NEI-funded Ophthalmic Clinical Trials

The Open Ophthalmology Journal 23 Oct 2023 RESEARCH ARTICLE DOI: 10.2174/0118743641266764231019092255



To describe the characteristics of trial design and statistical analysis of the National Eye Institute (NEI)-funded randomized clinical trials (RCTs) conducted after the year 2000.


Review of 42 NEI-funded ophthalmic RCTs.


Eligible trials were identified from ClinicalTrials.Gov and their primary result papers were identified from PubMed. Data on the design characteristics (primary outcome, number of arms, sample size, statistical power, inclusion of one eye or two eyes) and statistical analysis (statistical method for adjustment of inter-eye correlation, correction for multiple comparisons) as reported in the primary result paper were collected independently by two authors, and the differences were adjudicated by the senior author. Descriptive analyses were performed to summarize the characteristics of trial design and statistical analysis.

Main Outcome Measures:

Characteristics of trial design and statistical analysis.


Forty-two NEI-funded ophthalmic trials conducted after 2000 were included. The majority of trials were for evaluating the efficacy of drugs (57%), medical devices (21%), or procedures (14%) for the treatment of retinal diseases (45%) or pediatric eye diseases (45%). All trials were designed with at least 80% statistical power for comparing continuous (64%), binary (24%), or time-to-event (12%) primary outcome measures. In 11 (26%) trials enrolling both eyes of a participant, two eyes were in the same treatment group in 6 (55%) trials, and two-eye data were properly analyzed with adjustment for the inter-eye correlation when needed for all these trials. However, none of these trial publications explicitly stated that the inter-eye correlation was considered in the sample size and power calculation. In 13 trials with more than two arms, 12 (92%) trials adjusted for multiplicity using Bonferroni correction (42%), Hochberg procedure (42%) or Turkey’s method (17%).


While the availability of two eyes of a participant may complicate the ophthalmic trial design and statistical analysis, NEI-funded trials followed good practice in the trial design and statistical analysis, with enrollment of two eyes of a participant when appropriate, and adjustment of the inter-eye correlation in the statistical analysis. The sample size and power calculation can be improved by considering the inter-eye correlation and clearly reporting such information for future ophthalmic trials is important.

Keywords: Ophthalmic clinical trials, Trial design, Statistical analysis, Correlated eye data, RCTs, Drugs.
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