Non-inferiority trials in clinical ophthalmology: a systematic review.

PURPOSE

To summarize the characteristics and methodology of non-inferiority trials in ophthalmology, aiding researchers in understanding the applications and limitations of such trials in ophthalmic diseases.

METHODS

PubMed, Web of Science, Embase and Scopus were searched for literature on non-inferiority randomized trials in ophthalmology published between 2000 and November 5 2023. Data on the basic characteristics were extracted and summarized. The Risk of Bias 2's was used to assess the bias risk.

RESULTS

A total of 294 papers were included, with 77.6% of the trials conducted in the last 10 years, and more than 2/3 (72.1%) were multicenter studies, and 79.9% were registered on platforms. The majority of trials were applied in the researches of glaucoma, cataract, age macular degeneration, macular edema, dry eye, myopia, or refractive error. Non-inferiority thresholds were reported in 88.4% of the trials. Intent-to-treat analysis was the primary outcome analysis method in only 21.8% of trials, while both intent-to-treat and per-protocol analyses were used in 29.6%. Last observation carried forward method was used to address missing values in 23.5%. However, 56.5% of the articles did not report how missing values were handled, leaving uncertainty regarding whether missing data was considered in the analysis. About 20.7% of the studies were at high risk of bias, mainly due to outcome measures and missing value treatments.

CONCLUSION

Non-inferiority trials are commonly used in ophthalmologic research to assess the effectiveness, safety, cost-effectiveness of treatments or surgical methods, but the quality of implementation and reporting needs to be improved.