[R-meta] Between study correlation between two different outcomes

Viechtbauer, Wolfgang (SP) wolfg@ng@viechtb@uer @ending from m@@@trichtuniver@ity@nl
Wed May 9 10:46:02 CEST 2018

```Dear Matthias,

V should have the sampling *variances* along the diagonal. And yes, the off-diagonal values will be the covariances. Since you have two values per study, V will therefore be block-diagonal with 2x2 blocks along the diagonal. So your case is basically the same as this one:

http://www.metafor-project.org/doku.php/analyses:berkey1998

The issue of missing information about the covariances has been discussed on this mailing list quite extensively, so it would be good to browse through the archives.

One solution you will find mentioned there is ignoring the covariances (i.e., assuming that they are 0) and then using cluster-robust inference methods. This approach should be ok when interest is only on the fixed effects of the model. In your case, this approach is *NOT* appropriate, since you are specifically interested in the correlation between the random effects. If you assume that the covariances between the sampling errors is 0, then this will (usually) drive up the covariance between the random effects, which is going to lead to an overestimate of the correlation between the random effects. The cluster-robust approach fixes up the standard errors of the fixed effects, but won't do anything to correct for the bias in the estimated correlation between the random effects.

So, if you do not have any information to compute the covariances, you will have to make an educated guess and then do a sensitivity analysis.

Using the Berkey et al. (1998) data as an example, here is an illustration of what this might look like:

library(metafor)

dat <- get(data(dat.berkey1998))

cors <- seq(0, .99, length=100)
rhos <- rep(NA, length(cors))

for (j in 1:length(cors)) {

print(j)

### construct V matrix with guestimated correlation
V <- bldiag(lapply(split(dat[,c("v1i", "v2i")], dat\$trial), function(vi) {vi[1,2] <- vi[2,1] <- sqrt(vi[1,1] * vi[2,2]) * cors[j]; as.matrix(vi)}))

### multiple outcomes random-effects model
res <- rma.mv(yi, V, mods = ~ outcome - 1, random = ~ outcome | trial, struct="UN", data=dat)
rhos[j] <- res\$rho

}

plot(cors, rhos, type="o", pch=19)

So what I am doing here is constructing the V matrix based on the sampling variances and different assumed values for the correlation between the sampling errors (cors). Then I fit the model and save the correlation between the random effects (rhos). As you can see in the plot, as I assume a higher value for cor, the value for rho goes down. Assuming a correlation of 0 leads to an estimate of rho equal to 0.78. On the other hand, assuming a correlation of 0.9 leads to an estiamte of rho equal to 0.36. That's quite different.

I don't know to what extent rho will depend on the assumed correlation for your data. Also, I used a very wide range for 'cors' just for illustration purposes. In practice, you should be able to narrow down the range a bit more.

Best,
Wolfgang

-----Original Message-----
From: Aulbach, Matthias B [mailto:matthias.aulbach at helsinki.fi]
Sent: Wednesday, 09 May, 2018 10:07
To: Viechtbauer, Wolfgang (SP)
Subject: RE: Between study correlation between two different outcomes

Dear Wolfgang,

About the data structure: basically everything you assumed is correct. I have two rows for each study ("ID") ,first row outcome 1, second row outcome 2. "type_outcome" is a binary variable defining which kind of outcome is entered in which line.

And yes, the measurements are from the same subjects. The problem is that I don't have data about within-study correlations (or covariance), so I will have to make a guess about how large that is (or try out different values?). Is that right?
So as I understand, I need a 32x32-matrix with the diagonal being the standard errors from the studies and the off-diagonal values being my educated guess about the within-study covariance between the outcomes. Is that right?

Thank you once more for the help!

Best,
Matthias

-----Original Message-----
From: Viechtbauer, Wolfgang (SP) <wolfgang.viechtbauer at maastrichtuniversity.nl>
Sent: torstai 3. toukokuuta 2018 20.45
To: Aulbach, Matthias B <matthias.aulbach at helsinki.fi>; r-sig-meta-analysis at r-project.org
Subject: RE: Between study correlation between two different outcomes

Dear Matthias,

Can you explain the data structure a bit more? I assume you have two rows for each level of 'ID', the first row for outcome 1 and the second row for outcome 2 and that 'type_outcome' is a dummy variable to indicate the outcome. Is that correct?

Then the output should include the correlation between the underlying true effects (rho). You can get a CI for this with the confint() function. To test its significance, you can conduct a likelihood ratio test. This should do it:

rp <- rma.mv(yi, vi, data=pd, mod = ~ factor(type_outcome) -1, random= ~ type_outcome | ID)
rp0 <- rma.mv(yi, vi, data=pd, mod = ~ factor(type_outcome) -1, random= ~ type_outcome | ID, rho=0) anova(rp, rp0) confint(rp, rho=1)

Two notes:

The model you are fitting uses struct="CS" by default. This assumes that the amount of heterogeneity is the same for the two outcomes, which may not be appropriate. So you might want to use struct="UN".

Also, I assume the two outcomes are measured in the same subjects. In that case, the sampling errors of the two outcomes are correlated. So the V matrix (the second argument for the rma.mv()) function is not diagonal, but also should include the covariances. If you do not account for this, the correlation between the underlying true effects is very likely an overestimate.

Best,
Wolfgang

-----Original Message-----
From: R-sig-meta-analysis [mailto:r-sig-meta-analysis-bounces at r-project.org] On Behalf Of Aulbach, Matthias B
Sent: Thursday, 03 May, 2018 16:52
To: r-sig-meta-analysis at r-project.org
Subject: [R-meta] Between study correlation between two different outcomes

Hi,

I am conducting a meta-analysis, using the great metafor package. I have run into the problem of dependency when using more than one outcome from the same set of studies. In an earlier attempt, I had run two univariate meta-analyses and then used the outcome of one outcome as a predictor in a meta-regression with the other outcome as the dependent variable. But that ignores the within-study correlation between the two, so I'd like to improve that. So I'd like to handle that using a multivariate meta-analysis, using rma.mv and this line of code (with yi denoting the effect sizes, vi their standard errors, type_outcome the kind of outcome that was measured, and ID as the study identifier):

rp <- rma.mv(yi, vi, data=pd, mod = ~ factor(type_outcome) -1, random= ~ type_outcome | ID)

This nicely gives me the different effects for the two kinds of outcomes. However, what I am so desperately interested in is the between-study correlation between the two outcomes, i.e. if there's a strong effect on one outcome, is there also a strong effect on the other (or not)? Is there a way to get that information, including confidence intervals and a significance test for the correlation coefficient?

Any kind of advice is deeply appreciated!

Best,

Matthias

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