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The Barcelona study, conducted without commonplace registrational trial exclusions, reported the highest ACM, highlighting the potential limited generalizability of some industry trial results, as well as opportunities to increase enrollment and enrich for ACM. If the anticipated ACM rate is so low as to dictate a smaller NI margin to ensure the relative loss of efficacy at the extreme of the NI margin is not too large, then an ACM+ approach can be employed to increase the endpoint frequency. Defining SAEs and/or AEs post hoc is unacceptable. A better approach is employing the MedDRA toxic/septic shock SMQ to define the plus in an ACM+ endpoint. This endpoint could also add value as a sensitivity analysis, informing treatment effects on survivors. A weakness of the ACM endpoint is the exclusion of a majority of patients from analysis. Finally, use of an ACM+ endpoint could increase event rates at day 14 to a level compatible with a 10% NI margin. Is it methodologically appropriate to use ACM+ instead of ACM to increase the outcome event rate?The answer depends on whether the plus is important to how a patient feels or functions and would be impacted by antibiotic therapy. For example, an AE of gunshot wound after hospital discharge arguably should not be part of an ACM+ endpoint in a HABP/VABP study. However, plus events need not be rigidly pneumonia related eg, empyema but, rather, should include general infection related events such as those in the toxic/septic shock SMQ. Does an NI margin justification for ACM apply to an ACM+ endpoint: so called margin bridging?Our analyses for the HABP/VABP indications support the propositions that events from the toxic/septic shock SMQ can boost the endpoint event rate and that NI margin bridging allows the same NI margin for an ACM+ endpoint as for ACM.