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Randomized Controlled Trial
. 2021 Oct 1;139(10):1143-1144.
doi: 10.1001/jamaophthalmol.2021.3192.

Choice of Dose Level for a Randomized Clinical Trial of Low-Dose Bevacizumab vs Laser for Type 1 Retinopathy of Prematurity

Raymond T Kraker  1 , David K Wallace  2 , Roy W Beck  1 , Christina T Saunders  3 , Elizabeth Lorenzi  3 , B Michele Melia  1 , Zhuokai Li  1 ; Pediatric Eye Disease Investigator Group
Collaborators, Affiliations
Randomized Controlled Trial

Choice of Dose Level for a Randomized Clinical Trial of Low-Dose Bevacizumab vs Laser for Type 1 Retinopathy of Prematurity

Raymond T Kraker et al. JAMA Ophthalmol. .

Abstract

This study determines which of 8 doses of bevacizumab are effective in treating severe retinopathy of prematurity to carry forward to a large-scale randomized clinical trial.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kraker reported grants from the National Institutes of Health/National Eye Institute as coordinating center for the Pediatric Eye Disease Investigator Group during the conduct of the study. Drs Wallace and Beck reported grants from the National Eye Institute during the conduct of the study. Dr Saunders reported grants from Jaeb Center of Health Research Foundation during the conduct of the study. Dr Lorenzi reported personal fees from Jaeb Center of Health Research Foundation during the conduct of the study. Dr Melia reported grants from the National Eye Institute to their institution during the conduct of the study and nonfinancial support and grants from Regeneron for clinical trials run by the DRCR Retina Network investigating aflibercept outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Probability Each Dose Is at Least 95% Effective and Is the Lowest Effective Dose That Is at Least 95% Effective
A monotonic normal dynamic linear model was fit to the dose-response data. The probability of success for dose (d), pd, was estimated using a logistic function of the log odds for each dose, θd, where pd = exp(θd) / [1 + exp(θd)]. The model shares information across doses by setting a normal prior on the log odds, θd, where each θd has a mode of θd −1 with variance component τ2d.This prior structure borrows information from the previous dose to inform the log odds of success for the subsequent dose. The first dose is modeled with a normal distributed prior with mean (SD) of 0 (2). In addition, the model imposes monotonicity of θd, such that θd increases as a function of dose. Therefore, the model assumes that as the dose increases, the probability of success also increases. CrI indicates credible interval.
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Comment in

References

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