Vyluma, Inc.: atropine sulphate

'o have under the conditions of use prescribed, recommended, or suggested in its proposed labeling.

First, the study ailed its pre-specified hierarchical testing procedure.

Second, the study suffered from substantial and imbalanced missing data that creates a significant potential for bias, with the 0.01% arm exhibiting 25% missing data at the primary endpoint compared to 11% in the placebo arm and 14% in the 0.02% arm.

2-fold higher missing data rate in the 0.01% arm raises concerns that the data are not missing at random, and extensive sensitivity analyses that both you and FDA conducted could not adequately address these concerns.

Third, although you continued comparisons between the 0.01% strength and placebo outside of pre-specified formal statistical testing, there were significant flaws in your analyses regarding a treatment effect.

You conducted post-hoc analyses to support effectiveness of the 0.01% strength.

Such analyses were not statistically controlled, and they cannot overcome the fundamental failure of the pre-specified analyses.

These post-hoc analyses increase the risk of a type 1 error and thus increase the risk of finding a treatment effect when one does not exist.

, listed in this application, FDA conveyed deficiencies to the representative of the facility.

The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on the FDA Form 483 prior to your complete response.

The facility's satisfactory responses are dependent on FDA's determination that the facility has come into compliance with CGMP and may require re-inspection of the facility.

Following resolution of the CGMP inspection, FDA may need to conduct a Pre-Approval Inspection (PAI) of the facility.

Satisfactory outcomes of both the PAI and the CGMP surveillance inspections will be needed prior to an approval of the application.

Drops vs Placebo for Myopia Control, A Randomized Clinical Trial.