[R-meta] specification of phi in vcalc

Danielle Hiam d@n|e||e@h|@m @end|ng |rom de@k|n@edu@@u
Sun Aug 14 02:21:17 CEST 2022

```Hi James,

Very happy to share the data. To give you a brief overview, I am trying to run a correlated and hierarchical meta-analysis to investigate changes in microRNA expression after a acute bout of exercise. Each of the primary studies have differing time points so I have picked the most “common” timepoints (PRE, POST, 1-2hour post exercise and 24 hours post exercise) and dummy coded them as follows -1 (PRE), 0(POST), 1(within 1-2HP) and 2 (24HP). I have chosen to use the fold change from PRE as values as these would then be standard measurement across all the studies.

* How many studies you've got:
I am doing multiple meta-analysis of several microRNAs. To give you an idea miRNA-1 has 14 studies, miR-133a 16 studies etc...

* How many effect sizes per study (on average and the range of effect sizes per study; quartiles would be great too): miRNA-1: mean: 2.30 (total 46obs). miR-133a= mean 2.22 (total 51obs)
Average, median and IQR for miR-133a
Time  mean MEDIAN   IQR
1                  -1         1          1           0
2                   0      2.23      1.2         1.71
3                   1      1.54      1.49       1.08
4                  2       1.42      1.27      1.06

* Your model specification, including both what moderators are included and how you've specified the random effects:
This is my code:
V <- vcalc(FC_SD, cluster=cohort.in.study,
time1=Time_NUM, data = dat2,  phi=0.6)

rma.mv(yi = FC_MEAN,
V = V,
data = dat2,
mods = ~ factor(Time_NUM),
random = list (~ Time_NUM|cohort.in.study),
struct = "CAR")
As the timepoints are not evenly spaced but are dependent (repeated measures) I ran CAR for the struct argument.
Cohort.in.study is a unique ID to indicate that the timepoints within the cohort are dependent while timepoints outside this cohort are independent.

* For any included moderators, whether they are study-level characteristics (constant across the effect sizes for a given study) or effect-level characteristics (that vary within study).
I have chosen timepoints that are common across the studies (PRE, POST, 1-2hour post exercise and 24 hours post exercise). For example I dummy coded them as follows -1 (PRE), 0(POST), 1(within 1-2HP) and 2 (24HP)

* If you're open to sharing, the results of fitting the model with different values of phi, to provide a sense of how much the estimates change.
No worries see below for the miRNA-133a results. You will see while estimates don’t change drastically, the results from phi 0.4, 0.5 and 0.6 are borderline significant and when I change the phi to be above 0.7 they become significant. The QE also changes but it remains significant for all values of phi.

Phi 0.4                    estim   sqrt  fixed
tau^2      1.791  1.338     no
rho        0.000            no
Test for Residual Heterogeneity:
QE(df = 47) = 192.076,  p-val < .001
Model Results:
estimate    se¹   tval¹    df¹  pval¹  ci.lb¹  ci.ub¹     <U+200B>
intrcpt               0.983  0.040  24.415  12.72  <.001   0.896   1.070  ***
factor(Time_NUM)0     1.353  0.571   2.368  16.51  0.030   0.145   2.560    *
factor(Time_NUM)1     0.773  0.226   3.416  11.63  0.005   0.278   1.268   **
factor(Time_NUM)2     0.519  0.242   2.146   7.06  0.069  -0.052   1.089    .

Phi     0.5                estim   sqrt  fixed
tau^2      1.824  1.351     no
rho        0.000            no
Test for Residual Heterogeneity:
QE(df = 47) = 213.811,  p<0.001
Model Results:
estimate    se¹   tval¹    df¹  pval¹  ci.lb¹  ci.ub¹     <U+200B>
intrcpt               0.978  0.050  19.485  12.76  <.001   0.870   1.087  ***
factor(Time_NUM)0     1.361  0.580   2.348  16.45  0.032   0.135   2.587    *
factor(Time_NUM)1     0.800  0.235   3.409  11.56  0.005   0.286   1.313   **
factor(Time_NUM)2     0.541  0.240   2.257   7.05  0.058  -0.025   1.106    .

Phi     0.6                estim   sqrt  fixed
tau^2      1.865  1.366     no
rho        0.000            no
Test for Residual Heterogeneity:
QE(df = 47) = 249.228, p<0.001
Model Results:
estimate    se¹   tval¹    df¹  pval¹  ci.lb¹  ci.ub¹     <U+200B>
intrcpt               0.974  0.060  16.213  12.82  <.001   0.844   1.104  ***
factor(Time_NUM)0     1.369  0.588   2.328  16.39  0.033   0.125   2.614    *
factor(Time_NUM)1     0.822  0.244   3.376  11.48  0.006   0.289   1.356   **
factor(Time_NUM)2     0.564  0.239   2.358   7.01  0.050  -0.001   1.130    .

Phi     0.8                estim   sqrt  fixed
tau^2      1.965  1.402     no
rho        0.000            no
Test for Residual Heterogeneity:
QE(df = 47) = 439.477, p<0.001
Model Results:
estimate    se¹   tval¹    df¹  pval¹  ci.lb¹  ci.ub¹     <U+200B>
intrcpt               0.965  0.079  12.157  12.95  <.001   0.794   1.137  ***
factor(Time_NUM)0     1.387  0.606   2.291  16.27  0.036   0.105   2.670    *
factor(Time_NUM)1     0.857  0.262   3.265  11.24  0.007   0.281   1.433   **
factor(Time_NUM)2     0.612  0.246   2.493   6.90  0.042   0.030   1.194    *

-----Original Message-----
From: R-sig-meta-analysis <r-sig-meta-analysis-bounces using r-project.org> On Behalf Of James Pustejovsky
Sent: Thursday, 4 August 2022 1:12 PM
To: Lukasz Stasielowicz <lukasz.stasielowicz using uni-osnabrueck.de>
Cc: R meta <r-sig-meta-analysis using r-project.org>
Subject: Re: [R-meta] specification of phi in vcalc

Hi Danielle,

Just to add a little to Lukasz's suggestions (which I think are excellent), it is a little unusual and surprising that your results are very sensitive to changing the value of phi from 0.6 to 0.8. If you can provide a bit more detail about the structure of your data and model, I may be able to offer some suggestions on how to interpret this sensitivity. Specifically, it would be useful to know:
* How many studies you've got
* How many effect sizes per study (on average and the range of effect sizes per study; quartiles would be great too)
* Your model specification, including both what moderators are included and how you've specified the random effects
* For any included moderators, whether they are study-level characteristics (constant across the effect sizes for a given study) or effect-level characteristics (that vary within study).
* If you're open to sharing, the results of fitting the model with different values of phi, to provide a sense of how much the estimates change.

Incidentally, this issue is closely related to something I'm studying right
now: https://www.jepusto.com/talk/srsm-2022-matter-of-emphasis/

James

On Wed, Aug 3, 2022 at 10:14 AM Lukasz Stasielowicz < lukasz.stasielowicz using uni-osnabrueck.de> wrote:

> Dear Danielle,
>
> vcalc documentation contains a potentially helpful tip: "Argument phi
> must then also be specified to indicate the autocorrelation among the
> sampling errors of two effect sizes that differ by one unit on the
> time1 variable. As above, the autocorrelation of the measurements
> themselves can be used here as a proxy."
> https://rdrr.io/github/wviechtb/metafor/man/vcalc.html
>
> Perhaps some tables in primary studies show correlations between
> neighboring time points?
>
> Another option: If raw data are available for some primary studies,
> then one could estimate the correlation for several data sets and use
> it as "phi" input for vcalc. If different data sets lead to different
> values, then one could test different values in sensitivity analyses.
>
>
>
>
> Best,
> Lukasz
> --
> Lukasz Stasielowicz
> Osnabrück University
> Institute for Psychology
> Research methods, psychological assessment, and evaluation
> Seminarstraße 20
> 49074 Osnabrück (Germany)
>
> On 03.08.2022 12:00, r-sig-meta-analysis-request using r-project.org wrote:
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> >     1. specification of phi in vcalc (Danielle Hiam)
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> > Message: 1
> > Date: Wed, 3 Aug 2022 06:54:48 +0000
> > From: Danielle Hiam <danielle.hiam using deakin.edu.au>
> > To: "r-sig-meta-analysis using r-project.org"
> >       <r-sig-meta-analysis using r-project.org>
> > Subject: [R-meta] specification of phi in vcalc
> > Message-ID:
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> ME3PR01MB54642B304670F1BF825E6F60B79C9 using ME3PR01MB5464.ausprd01.prod.out
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> > Content-Type: text/plain; charset="iso-8859-1"
> >
> > Hello,
> >
> > I am running a meta-analysis that has nested data and dependent
> > effect
> sizes (multiple timepoints). Therefore, I need to take into account
> effect sizes that are correlated and also cluster within studies. I
> will run vcalc, then the rma.mv function and then use robust with
> clubsandwich set to true to "correct" for any mis-specification of the
> model. However, I am looking for some clarification regarding how to
> "guess" the value for phi in the vcalc function, R code: V <-
> vcalc(FC_SD, cluster, time1=Time_NUM, data, phi=0.6).
> >
> > When I change phi from 0.6 to 0.8 in vcalc I get very different
> > results
> from the meta-analysis (rma.mv followed by robust(.... Clubsanwich=T).
> I have read James Pustejovsky paper (DOI:
> https://doi.org/10.1007/s11121-021-01246-3) on this, where he suggests
> that in situations where no information is available, the meta-analyst
> might pick a plausible value and then conduct sensitivity analysis
> >
> > Any information regarding specification of phi would be greatly
> appreciated
> >
> > Thanks,
> > Danielle
> >
> > Deakin University
> > Melbourne Burwood Campus, 221 Burwood Highway, Burwood VIC 3125
> > danielle.hiam using deakin.edu.au ipan.deakin.edu.au Deakin University
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