Rivaroxaban for the treatment of deep vein thrombosis and ...

depends on the specific parameterisation. In addition, when there is relatively little sample data being
analysed, the prior information can dominate and should be described with care.
NICE DSU TSD2 states that it has become standard practice to use a uniform prior distribution on the
range (0, 2) for the between-study standard deviation for log-odds ratios and log hazard ratios.
However, the document also notes that there are major disadvantages in routinely using vague prior
distributions because, in the absence of a reasonable number of large trials, the posterior distribution
of the between-study standard deviation will be poorly identified and likely to include values that are
implausibly high or possibly implausibly low and will not represent reasonable beliefs.
In this STA, the analyses were conducted using a uniform prior distribution on the range (0, 5) for the
between-study standard deviation when analysing hazard ratios and odds ratios. Although this was
taken from the WinBUGS code included in NICE DSU TSD2, it is even more extreme than that
described with caution in Section 6.2. Half of the analyses included four or less data points and there
are not many more data points available in the primary analyses. Consequently, the prior distribution
for the between-study standard deviation will have a large impact on the results. In fact, as a
consequence of the prior distribution not representing genuine prior beliefs then, without much
Bayesian updating of the prior distribution for the between-study standard deviation to its posterior
distribution, the posterior distributions for the treatment effects will not represent meaningful beliefs.
In the clarification letter, the ERG attempted to encourage the manufacturer to consider using a more
informative prior distribution for the between-study standard deviation so as to avoid implausible
estimates of treatment effect. Unfortunately, this question was not interpreted as the ERG had
intended. NICE DSU TSD2 discusses the use of alternative prior distributions for the between-study
standard deviation when there are a limited number of studies. The ERG believes that a uniform prior
distribution on the range (0, 0.6) would have provided a more reasonable choice for the between-study
standard deviation in the absence of a reasonable number of studies; this prior distribution is still
reasonably uncertain and it acknowledges the possibility of moderate heterogeneity between studies.
The ERG re-analysed the primary data using a uniform prior distribution for the between-study
standard deviation on the range (0, 5) as used in the MS, a uniform prior distribution on the range (0,
2), as recommended in NICE DSU TSD2, and a uniform prior distribution on the range (0, 0.6) as a
sensitivity analysis. These analyses are presented in section 4.5.
When using a uniform prior distribution for the between-study standard deviation on the range (0, 5)
the means of the posterior distributions are greater than the 97.5%-iles, suggesting that the
distributions for the treatment effects are highly skew and essentially unstable.
76
Copyright 2012 Queen's Printer and Controller of HMSO. All rights reserved.