In this episode, mechanisms and research are discussed. The question, ‘if we have a randomized control trial (RCT), can we do without knowledge of a mechanism?’ is answered. It is held that mechanisms do make a substantive difference to the optimization of a RCT. This is defended through two cases — the failed Duchenne Muscular Dystrophy Phase 3 trials in 2024 ran by Sarepta Therapeutics and Pfizer and the daptomycin 2005 trial to test its efficacy in patients Gram-positive community acquired pneumonia. Nancy Cartwright’s INUS contributors are put forth as a potential objection. However, an as-complete-as-possible concept of mechanistic understanding and reasoning is advocated for ultimately.