Comparison of Clinical Trial and Systematic Review Outcomes for the 4 Most Prevalent Eye Diseases

Abstract

Importance: Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies.

Objectives: To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews.

Design, setting, and participants: This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease.

Main outcomes and measures: Proportion of review outcomes also reported in trials and vice versa.

Results: This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews.

Conclusions and relevance: Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.

Figure 1.. Hypothetical Scenarios Showing Proportion of Trials Reporting and Proportion of Reviews Naming Each Outcome

Each dot refers to 1 outcome. White dots indicate outcomes measured by all trialists and reviewers.

Figure 2.. Overlap Between Outcomes in Reviews and Trials by Disease

Outcomes in 15 reviews and 79 trials of age-related macular degeneration (A), 15 reviews and 138 trials of cataract (B), 6 reviews and 55 trials of diabetic retinopathy (C), and 20 reviews and 142 trials of glaucoma (D).

Figure 3.. Scatterplot Showing Proportion of Trials Reporting and Proportion of Reviews Naming Each Outcome by Disease

For age-related macular degeneration, 110 outcomes were reported in 79 trials and 15 reviews (A); cataract, 108 outcomes in 138 trials and 15 reviews (B); diabetic retinopathy, 61 outcomes in 55 trials and 6 reviews (C); and glaucoma, 96 outcomes in 142 trials and 20 reviews (D). Each dot refers to 1 outcome.