[R-meta] What asymmetry test to use?

[Dr. Guido Schwarzer]

Martin,

The large between-study heterogeneity might be due to including both studies comparing drugs with placebo and drugs with other drugs. Furthermore, the (slight) asymmetry in your funnel plot might be due to between-study heterogeneity which was already described in the paper introducing the Egger test as a potential source of asymmetry (Egger et al., 1997, BMJ).

You could look at a funnel plot of studies comparing drugs with placebo. However, if drugs have a different efficacy, you might get an asymmetric funnel plot due to heterogeneity.

A funnel plot of drugs vs other drugs is not well defined as you might include studies comparing A vs B or B vs A (and similarly for any other drug comparison).

All this said, I would argue that your setting (studies comparing drugs with placebo and drugs with other drugs) calls for the conduct of a network meta-analysis. If you would go this route, the paper by Chaimani and Salanti (https://onlinelibrary.wiley.com/doi/10.1002/jrsm.57) gives a nice introduction into the evalution of small study effects in network meta-analysis and introduces the comparison-adjusted funnel plot.

Best,
Guido