Potential effects of vitamin A and E supplementation in the whole RP cohort.
RP
It was not our intention to reevaluate the conclusions of the original study regarding vitamin A and E supplementation in the broader group of all typical RP patients, since the initial goal was to evaluate which genetic subgroups might best respond to vitamin A. However, the data surprisingly indicated that there was no overall robust effect of vitamin A when additional data plus a predictive biomarker were included in the analyses. It is always possible that different data processing or statistical techniques could have uncovered a treatment effect of vitamin A. As described in the Methods, we intentionally maintained data processing procedures as close as possible to those used in the original analysis, including use of a minimum starting ERG amplitude when estimating progression rates, and use of an average of both eyes’ amplitudes. We cannot rule out that alternative processing would be more sensitive. An additional floor cutoff at non-baseline visits and explicit modeling of right versus left eye values have been used in later studies, but these techniques were not used in this study in order to most closely replicate the original data processing of the original vitamin A study. As this result was surprising, we invested additional resources into expanding the sample size using participants in the subsequent trials. These extra participants did not make a fundamental difference in estimating the vitamin A and E treatment effects, but did further enhance the natural history and genetic solutions data set.The updated analyses in this study also do not change the structure of the original data. It continues to be the case that the last 2 years of the original analysis contained fewer participants than in the original 4 years, even with additional data from after the original data lock. It has already been noted that the emergence of the vitamin A and E effects occurred in those latter years, where those data were more dispersed (Figure 5 of Berson et al., ref. 