Goldilocks and the three post-cardiac arrest subjects

      Clinical trials conducted in the intensive care setting are often neutral [
      • Harhay M.O.
      • Wagner
      • Ratcliffe S.J.
      • Bronheim R.S.
      • Gopal A.
      • Green S.
      • et al.
      Outcomes and statistical power in adult critical care randomized trials.
      ]. To some extent, this may be explained by issues of statistical power, recruitment, and outcome selection common to all clinical trials. However, the role of heterogeneity of disease severity or unmeasured patient factors may play a larger role [
      • Vincent J.L.
      We should abandon randomized controlled trials in the intensive care unit.
      ]. In conventional trial designs, population-average treatment effects are compared between arms. If a particular therapy helps a third of subjects, hurts a third of subjects and is inert in the remaining third, it will appear to have no benefit compared to placebo.
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