Does evidence support the high expectations placed in precision medicine? A bibliographic review [version 1; peer review: 2 approved with reservations, 1 not approved]

Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient's individual characteristics. However, the conventional design of randomized trials assumes that each individual benefits by the same amount. Methods: We reviewed parallel trials with quantitative outcomes published in 2004, 2007, 2010 and 2013. We collected baseline and final standard deviations of the main outcome. We assessed homoscedasticity by comparing the outcome variability between treated and control arms. Results: The review provided 208 articles with enough information to conduct the analysis. At the end of the study, 113 (54%, 95% CI 47 to 61%) papers find less variability in the treated arm. The adjusted point estimate of the mean ratio (treated to control group) of the outcome variances is 0.89 (95% CI 0.81 to 0.97). Conclusions: Some variance inflation was observed in just 1 out of 6 interventions, suggesting the need for further eligibility criteria to tailor precision medicine. Surprisingly, the variance was more often smaller in the intervention group, suggesting, if anything, a reduced role for precision medicine. Homoscedasticity is a useful tool for assessing whether or not the premise of constant effect is reasonable.