Page Rev Bayes – we found statistical irregularities in a randomized controlled trial

November 9, 2013
By

(This article was first published on Statistical Reflections of a Medical Doctor » R, and kindly contributed to R-bloggers)

The Bayesian counterpart to the frequentist analysis of the Randomized Controlled Trial is in many aspects more straightforward than the Bayesian analysis. One starts with a prior probability about the probability of a patient being assigned to each of the three arms and combines it with the (multinomial) likelihood of observing a given assignment pattern in the 240 patients enrolled in the study. Bayes theorem gives the posterior probability quantifying our belief about the magnitudes of the unknown assignment probabilities. Note that testing the strict equality is bound to lead us straight to the arms of the Lindley paradox so that a different approach is likely to be more fruitful. Specifically, we specify a maximum tolerable threshold for the difference between the maximum and the minimum probability of being assigned the trial arms (let’s say 1-5%) and we directly calculate the probability for this difference (“probability of foul play”).

In the absence of prior evidence for (or against) foul play we use a non-informative prior in which all possible values of assignment probabilities are equally plausible. This (Dirichlet) prior corresponds to a prior state of knowledge in which three individuals were randomized and all three ended up in different treatment arms. Under this prior, the posterior distribution is itself a Dirichlet distribution with parameters equal to the number of individuals actually assigned to each arm+1. The following R code may then be used to calculate the probability of foul play, as previously defined i.e.

 event<-c(105,70,65)
set.seed(1234);
r<-rdirichlet(10000,event+1);
res0<-mean(apply(r,1,function(x,tol)
I(abs(max(x)-min(x))<=tol),0.01))
res0*100

This probability comes down to 0.4% which is numerically close to the frequentist answer, yet with a more intuitive interpretation: based on the observed trial sizes and a numerical tolerance for the maximum tolerable difference in assignment probability the odds for “foul play” are 249:1.
Increasing the tolerance will obviously decrease these odds, but in such a case we would be willing to tolerate larger differences in assignment probabilities. Although these results are mathematically trivial (and non-controversial), the plot will become more convoluted when one proceeds to use them to make a declaration of “foul play”. For in that case, a decision needs to be made which has to consider not only the probability of the uncertain events: “foul play” v.s. “not foul play” but also the consequences for the journal, the study investigators and the scientific community at large. At this level one would need to decide whether the odds of 249:1 are high enough or not for subsequent action to be taken. But this consideration will take us to the realm of decision theory (and it already 11pms).

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