Strengths and limitations
EMA
The presented results have to be considered against the backdrop of the strengths and limitations of previously published work. Due to the strict inclusion and exclusion criteria, the study was unable to yield the expected sample size of 30 patients in the allotted time. Such a sample size would have been necessary to provide sufficient statistical power for the primary intention-to-treat analysis which was not statistically significant, most likely due to the limited power originating from the small sample size and the categorial nature of the primary outcome parameter. Post-hoc estimates of statistical power indicated that the power to detect effect sizes corresponding to a HR of 0.73 was <15%. To illustrate the magnitude of the effect of DBS in treatment resistant AUD, we calculated the corresponding NNT, which indicated a medium effect of DBS in AUD. The wide confidence interval of the estimate for the NNT, however, indicates a high degree of uncertainty regarding the size of the true effect and should therefore be interpreted with caution. Inclusion of a parametric primary outcome could have provided higher power. Unfortunately, the use of such outcomes (e.g. mean alcohol use, proportion of heavy drinking days) had not yet been approved by the European Medicines Agency (EMA) when we planned and received funding for our study, and thus were not approved by the ethics boards. Future studies should consider outcomes beyond abstinence rates, such as number of heavy drinking days, which captured significant effects of NAc DBS in the current study. The sample of our study can still be considered as sizable in the light of the very low sample sizes of previous DBS AUD studies in the literature (range 