For the NEQ approach, analytical error estimates can help detect lack of overlap of the work distributions. For maximum likelihood methods, like BAR, the variance asymptotically converges to the inverse of the Fisher information of the joint distribution of, in this case, forward and reverse work values. Using this variance estimate, the analytical uncertainty can be vastly overestimated when overlap is poor (Sec. 5.5 and especially Figure ). We therefore only use this method as a diagnostic metric in the NEQ approach. A high uncertainly estimate indicates a potential overlap problem and that results cannot be trusted.