Friday 16 December 2016

When is a replication not a replication?

Replication studies have been much in the news lately, particularly in the field of psychology, where a great deal of discussion has been stimulated by the Reproducibility Project spearheaded by Brian Nosek.

Replication of a study is an important way to test the the reproducibility and generalisability of the results. It has been a standard requirement for publication in reputable journals in the field of genetics for several years (see Kraft et al, 2009). However, at interdisciplinary boundaries, the need for replication may not be appreciated, especially where researchers from other disciplines include genetic associations in their analyses. I’m interested in documenting how far replications are routinely included in genetics papers that are published in neuroscience journals, and so I attempted to categorise a set of papers on this basis.

I’ve encountered many unanticipated obstacles in the course of this study (unintelligible papers and uncommunicative authors, to name just two I have blogged about), but I had not expected to find it difficult to make this binary categorisation. But it has become clear that there are nuances to the idea of replication. Here are two of those I have encountered:

a)    Studies which include a straightforward Discovery and Replication sample, but which fail to reproduce the original result in the Replication sample. The authors then proceed to analyse the data with both samples combined and conclude that the original result is still there, so all is okay. Now, as far as I am concerned, you can’t treat this as a successful replication; the best you can say of it is that it is an extension of the original study to a larger sample size.  But if, as is typically the case, the original result was afflicted by the Winner’s Curse, then the combined result will be biased.
b)    Studies which use different phenotypes for Discovery and Replication samples. On the one hand, one can argue that such studies are useful for identifying how generalizable the initial result is to changes in measures. It may also be the only practical solution if using pre-existing samples for replication, as one has to use what measures are available. The problem is that there is an asymmetry in terms of how the results are then treated. If the same result is obtained with a new sample using different measures, this can be taken as strong evidence that the genotype is influencing a trait regardless of how it is measured. But when the Replication sample fails to reproduce the original result, one is left with uncertainty as to whether it was type I error, or a finding that is sensitive to how it is measured. I’ve found that people are very reluctant to treat failures to replicate as undermining the original finding in this circumstance.

I’m reminded of arguments in the field of social psychology, where failures to reproduce well-known phenomena are often attributed to minor changes in the procedures or lack of ‘flair’ of experimenters. The problem is that while this interpretation could be valid, there is another, less palatable, interpretation, which is that the original finding was a type I error.  This is particularly likely when the original study was underpowered or the phenotype was measured using an unreliable instrument. 

There is no simple solution, but as a start, I’d suggest that researchers in this field should, where feasible, use the same phenotype measures in Discovery and Replication samples. Where that is not feasible, the could pre-register their predictions for a Replication Sample prior to looking at the data, taking into account the reliability of the measures of the phenotype and the power of the Replication Sample to detect the original effect, based on the sample size

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