Limitations
There are several important limitations to the trial. First, the original dosing protocol was changed on the advice of the Data Safety Monitoring Board based on results of the first 51 completers, owing to lack of efficacy. Data indicating the bioavailability of subcutaneous ketamine to be about 0.66 were not available when the present study was designed,As with phase 3 trials of esketamine, final ratings were conducted by independent raters masked to treatment allocation. However, in contrast to the trials of esketamine, efficacy and safety were tested against an active control drug with psychoactive effects to facilitate masking, and there was a formal evaluation of masking (which remains the exception rather than the norm in trials in this area and in psychiatry trials more broadly).