THE REPORTING QUALITY OF NONINFERIORITY TRIALS USING INTRAVITREAL VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS.

Purpose: Noninferiority trials (NIFTs) are widely used to study intravitreal vascular endothelial growth factor inhibitors for the treatment of ocular diseases. Thus, this trial design deserves greater attention. We aimed to comprehensively assess the methodological and reporting quality of NIFTs in the field of neovascular ocular diseases.

Methods: We identified NIFTs using antivascular endothelial growth factor agents published before February 2020 from PubMed and Web of Science. Two independent authors extracted and double-checked predefined elements related to the quality of design and reporting. The characteristics and reporting of NIFTs were described with frequencies and percentages. We summarized important factors that were potentially biased the results of NIFTs and provided point-to-point recommendations.

Results: In total, 34 studies involving 15,190 subjects and 51 pairs of noninferiority comparisons were identified. Areas of concern that could potentially affect the qualities of NIFTs included the absence of justification for the selection of noninferiority margins (61.8%), the use of unusually wide noninferiority margins (26.5%), the lack of outcome confirmation provided by the intention-to-treat and per-protocol analyses (64.7%), the presence of postrandomization exclusions >10% (52.9%), and not declaring the compensatory benefits (35.3%). Moreover, industry-sponsored NIFTs were more likely to draw positive results (P = 0.036).

Conclusion: NIFTs of antivascular endothelial growth factor therapies commonly achieved noninferiority of the tested intervention. However, the methodologies and reporting limitations may affect the confidence of the results. Thus, more awareness must be created among investigators for better adherence to guidelines and recommendations while designing, conducting, and reporting on NIFTs.