None of these studies provide a systematic assessment of the effect of various parameters involved in the complex setup of alchemical ABFE calculations, selecting arbitrary values for such parameters in their calculations without justification. Some authors recognise the importance of performing ensemble simulations to capture the true uncertainty in ABFE predictions by acknowledging that errors obtained through bootstrapping underestimate it (even after using decorrelated samples) . However, even in these handful of studies, the choices of ensemble size (often variously referred to as "independent repeats" or "replicates") are not systematic but ad hoc. Baumann et al. and Chen et al. use an ensemble size of 3, whereas Khalak et al. use 5. Gapsys et al. vary ensemble size from 3 to 5 for their equilibrium ABFE calculations but use larger ensembles (sizes between 5 and 20) for their non-equilibrium ABFE calculations depending on the system and the free energy component being calculated. However, none of the above mentioned studies perform any systematic investigation to arrive at an "appropriate" ensemble size, nor do they provide any justification for their choices.