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[R-meta] metagen / low heterogeneity

6 messages · Sean, Guido Schwarzer, Emerson Del Ponte +1 more

#
Hello Meta-analysis Community,

I've been using the metagen function in the meta package for a
meta-analysis on fungicide efficacy to control a foliar pathogen in
cucumbers. I'm using pre-calculated Hedge's G as my effect size and it's
standard error. I'm not really a statistician, so I've been using this
resource to hold my hand through the process (
https://bookdown.org/MathiasHarrer/Doing_Meta_Analysis_in_R/random.html).
I've run into a bit of a rut and I'm having a hard time getting help to
interpret my results. I'm dealing with the issue of some of my dataset
heterogeneity being nearly 0 (which could just be the case).

*Here is an example of my output:*

Number of studies combined: k = 288

                                    SMD      95%-CI                t
p-value
Random effects model 0.3309 [ 0.2866; 0.3751] 14.72 < 0.0001
Prediction interval                     [-0.2216; 0.8834]

Quantifying heterogeneity:
 tau^2 = 0.0783 [<0.0000; <0.0000]; tau = 0.2798 [<0.0000; <0.0000];
 I^2 = 0.0% [0.0%; 0.0%]; H = 1.00 [1.00; 1.00]

Test of heterogeneity:
      Q     d.f.   p-value
 165.46  287  1.0000

*Here is the code:*

metamkt <- metagen(G,
                    seG,
                    data = mkt,
                    studlab = paste(Study),
                    comb.fixed = FALSE,
                    comb.random = TRUE,
                    method.tau = "SJ",
                    hakn = TRUE,
                    prediction = TRUE,
                    sm = "SMD")

My first red flag is of course "I^2 = 0.0%", then that my Q p-value is 1.
The interpretation being that the observed heterogeneity is completely
random. I have a couple datasets, with the highest I^2 = 17.4%. The reason
I find it odd, is that when I do subgroup analysis (even though I'm not
supposed to with such low / non-existat heterogeneity), the results make
biological sense. My data spans the last decade and the results are also
similar with a meta-analysis done in the previous decade on the same topic.
This makes me feel like I've made some sort of error at some point in my
workflow and I was wondering if you have any diagnostic recommendations for
me? One thing that worries me is that my standard errors for my Hedge's G
values are so similar since all treatments in each study have 4
replications, but maybe it shouldn't.

Best,

Sean
#
Dear Sean

Some comments in-line. It is difficult to read your output because you 
posted in HTML so I will leave that to people more familiar with the 
software. Next time it would help to set your mailer to use plain text 
so your message does not get mangled.
On 11/01/2021 14:56, Sean wrote:
The fact that your prediction interval is so much wider than the 
confidence interval does suggest there is heterogeneity here.
No, no, a thousand times no. You use a moderator if there is a 
scientific hypothesis which justifies it not because of observed 
heterogeneity. In this case if there is a biological theory behind a 
moderator then use it.

Michael

  My data spans the last decade and the results are also

  
    
  
#
I apologize for the formatting. Here is the ouput and code again
below. I think this should be more readable now that I've selected
plain text.

Michael, well that is good news. If I did have high heterogeneity and
hadn't planned to use a moderator, does that just mean I should
consider looking for one? Whereas in my case, I knew what I was
interested in, so my heterogeneity does not need to be considered as a
prerequisite?

Here is an example of my output:

Number of studies combined: k = 288

                                    SMD      95%-CI                t
     p-value
Random effects model 0.3309 [ 0.2866; 0.3751] 14.72 < 0.0001
Prediction interval                     [-0.2216; 0.8834]

Quantifying heterogeneity:
 tau^2 = 0.0783 [<0.0000; <0.0000]; tau = 0.2798 [<0.0000; <0.0000];
 I^2 = 0.0% [0.0%; 0.0%]; H = 1.00 [1.00; 1.00]

Test of heterogeneity:
      Q     d.f.   p-value
 165.46  287  1.0000

Here is the code:

metamkt <- metagen(G,
                    seG,
                    data = mkt,
                    studlab = paste(Study),
                    comb.fixed = FALSE,
                    comb.random = TRUE,
                    method.tau = "SJ",
                    hakn = TRUE,
                    prediction = TRUE,
                    sm = "SMD")

Sean
On Mon, Jan 11, 2021 at 11:11 AM Michael Dewey <lists at dewey.myzen.co.uk> wrote:
#
Sean,

The confidence intervals for tau2 and tau are certainly wrong / meaningless.

I could have a closer look if you send me (part of) your data set with 
these strange CIs.

Best wishes
Guido

P.S. Internally, meta calls rma.uni() and confint() from R package 
metafor to calculate the confidence intervals for tau2 and tau. I do not 
assume that there is a problem in the computations in metafor.
#
Dear Sean,

I have been dealing with this kind of data and context (fungicide effect on
plant disease), and I think I know which is the previous paper you are
basing your analyses. Sorry for not replying to your specific questions,
but it seems there are primary aspects to look at before specificities of
the MA outcome.

I would recommend that you give a look at a number of works that followed
in the last decade (in case you didn't do it). I am quite sure that you are
treating several treatments from the same experiment as independent given
your high K - all treatments from the same trial are compared to a common
control. A network MA should be interesting to test. I've used the
arm-based approach in metafor (Wolfgang's help) and the contrast-based in
netmeta (Gerta's help).

Nothing wrong with Hedges G, but I would argue that log ratio is a more
directly interpretable effect size in our area - You really want to know
(as everybody in our field) the percent reduction in disease due to
fungicide use relative to the untreated check. The absolute or standardized
difference can be complicated if your control varies considerably among the
trials. Also, the criteria to classify and interpret Hedges G are not well
established in our field.

If you want to see examples specific for this kind of situation, I have
several codes on my github (check the link to the html report for each of
these):

https://github.com/emdelponte/paper-FHB-mixtures-meta-analysis
https://github.com/emdelponte/paper-fungicides-whitemold
https://github.com/emdelponte/paper-FHB-Brazil-meta-analysis

Hope this helps!

Emerson



Em seg., 11 de jan. de 2021 ?s 11:57, Sean <sean.toporek at gmail.com>
escreveu:

  
    
#
On 11/01/2021 16:45, Sean wrote:
The crucial thing is the scientific context. I do not work in the same 
area as you so my examples are from my field, not yours, but I hope are 
helpful.

If the primary studies were all very similar then you would not expect 
heterogeneity and you might be prompted to look for explanations for 
even mild amounts. For instance if all the primary studies had studied 
the same dose of drug in people with very tightly defined illness in 
countries with very similar health care symptoms then any heterogeneity 
might lead you, post hoc, to find out why.

If on the contrary the studies had examined a complex health care 
systems intervention in countries across the globe in patients who might 
vary considerably then you would be very surprised not to see 
heterogeneity. In that case you would be less inclined to look for 
explanations.

If you had a theory that outcomes were related to some other variable 
then you might use that as a moderator irrespective of the amount of 
heterogeneity. For instance in a study of a skills-based therapy you 
might have a theory that outcomes are different now from what they used 
to be so you would find it worth while looking at that whatever. For 
instance is centres in each study have been doing a particular operation 
for different amounts of time do the ones who have been doing it for 
longest have have better or worse outcomes.

Michael