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Our paper differs from previous literature in two ways 1.We think in terms of clinical consequences, what benefits patients, what harms patients. Our main message is using a not logic-respecting efficacy measure can potentially harm patients in a randomized controlled trial (RCT), as we prove analytically, and demonstrate with the OAK blood-based tumor mutational burden (bTM study. 2.We follow nature, which mixes effects within each treatment arm. Our secondary message is that following nature to mix within each treatment arm first b