The science of n=1

We are longitudinal creatures. As HG Wells wrote in the introductory exposition of The Time Machine, 'any real body must have extension in four directions: it must have Length, Breadth, Thickness, and—Duration'. We know this in clinical medicine, where the most valuable ingredient of diagnosis, prognosis, and therapy is often time. And yet much of observational medical research is cross-sectional - we compare two groups at the same time, condensing all nuance of an individual's life-course into the variance of the group.

N=1 trials are of increasing interest because they take full advantage of the fact that intra-individual variation is almost always much less than inter-individual variation. Plus they more directly answer the question we really care about - will this intervention help this person?

A great recent example was the SAMSON study, which looked at side-effects reported by patients taking statins to lower cholesterol. Despite the significant benefits of statins for both primary and secondary prevention of cardiovascular disease (the global number one killer), there has been much media attention given to reported side-effects. In SAMSON, patients who had previously stopped statins due to side-effects agreed to take statins again, but this time in a random sequence of months interchanging with placebo. 90% of the side-effects associated with statins also occurred on placebo, and 50% of the participants were able to restart statins.

(As is often the case, the most interesting part of this study is reported in the Supplementary Materials. On p.18 we see the reasons that people declined to take part in the study. Here were have the immortal comment 'Fed up with doctors poking at me because of my hereditary problem'.)

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