Abstract
Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient's individual characteristics. However, conventional clinical trials are designed to find differences in averages, and interpreting these differences depends on untestable assumptions. Although only an ideal, a constant effect of treatment would facilitate individual management. A direct consequence of a constant effect is that the variance of the outcome measure would be the same in the treated and control arms. We reviewed the literature to explore the similarity of these variances as a foundation for examining whether and how often precision medicine is definitively required. Methods: We reviewed parallel clinical trials with numerical primary endpoints published in 2004, 2007, 2010 and 2013. We collected the baseline and final standard deviations of the main outcome measure. We assessed homoscedasticity by comparing the variance of the primary endpoint between arms through the outcome variance ratio (treated to control group). Results: The review provided 208 articles with enough information to conduct the analysis. One out of five studies (n = 40, 19.2%) had statistically different variances between groups, implying a non-constant-effect. The adjusted point estimate of the mean outcome variance ratio (treated to control group) is 0.89 (95% CI 0.81 to 0.97). Conclusions: The mean variance ratio is significantly lower than 1 and the lower variance was found more often in the intervention group than in the control group, suggesting it is more usual for treated patients to be stable. This observed reduction in variance might also imply that there could be a subgroup of less ill patients who derive no benefit from treatment. This would require further study as to whether the treatment effect outweighs the side effects as well as the economic costs. We have shown that there are ways to analyze the apparently unobservable constant effect.
Highlights
The goal of precision medicine is to develop prevention and treatment strategies that take into account individual characteristics
First, to compare the variability of the main outcome between arms in parallel randomized controlled trials published in medical journals; and, second, to provide a rough estimate of the proportion of studies that could potentially benefit from precision medicine
The majority of the selected studies were non-pharmacological (122, 58.6%); referred to chronic conditions (101, 57.4%); had a continuous outcome measured with units (132, 63.8%) instead of a constructed scale; had an outcome that was measured (125, 60.1%) rather than assessed; and had lower values of the outcome indicating positive evolution (141, 67.8%)
Summary
The goal of precision medicine is to develop prevention and treatment strategies that take into account individual characteristics. As Collins and Varmus stated, “The prospect of applying this concept broadly has been dramatically improved by recent developments in large-scale biologic databases (such as the human genome sequence), powerful methods for characterizing patients (such as proteomics, metabolomics, genomics, diverse cellular assays, and mobile health technology), and computational tools for analyzing large sets of data.”. With this words in mind, US President Obama gave his strong endorsement in launching the 2015 Precision Medicine initiative to capitalize on these developments[1,2]. We assessed homoscedasticity by comparing the variance of the primary endpoint between arms through the outcome variance ratio
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