Results from studies examining the treatment of fibromyalgia syndrome with various antidepressants.

dat.haeuser2009

Format

The data frame contains the following columns:

studycharacterstudy authors
refnumericreference number as in article
yearnumericpublication year
countrynumericcountry where study was conducted
femalenumericpercent of female participants
whitenumericpercent of white participants
magenumericmean age of participants
durationnumericstudy / treatment duration
mednumericantidepressant medication
jadadnumericJadad score
vantuldernumericvan Tulder score
tgrpnumerictreatment group identifier
cgrpnumericcontrol group identifier
outcomenumericoutcome variable
typenumericwhether means reflect raw means of mean changes
ntinumericnumber of participants in the treatment group
mtinumericmean (change) in the treatment group
sdtinumericstandard deviation in the treatment group
ncinumericnumber of participants in the control group
mcinumericmean (change) in the control group
sdcinumericstandard deviation in the control group

Details

The meta-analysis by Häuser et al. (2009) examined the efficacy of antidepressants in the treatment of fibromyalgia syndrome. Several outcomes were assessed in the studies, including pain, fatigue, sleep, (depressed) mood, and health-related quality of life (variable outcome).

Note

Some studies compared multiple treatment groups against a common control group. This induces dependency between the observed standardized mean differences, which was not accounted for in the analyses conducted in the original meta-analysis.

If a range was given in the dataset (e.g., for variable female), then the midpoint of the range was entered in the dataset.

Some typos were discovered and corrected during data entry. For Heymann et al. (2001), the mean in the nortiptyline group for was 48.78, not 49.78. For Hannonen et al. (1998), the sample size of the treatment group for outcome sleep was 30, not 39.

Source

Häuser, W., Bernardy, K., Üçeyler, N., & Sommer, C. (2009). Treatment of fibromyalgia syndrome with antidepressants: A meta-analysis. Journal of the American Medical Association, 301(2), 198–209. https://doi.org/10.1001/jama.2008.944

Concepts

medicine, standardized mean differences, multilevel models, cluster-robust inference

Examples

### copy data into 'dat' and examine data
dat <- dat.haeuser2009
dat
#>                study ref year       country female white mage duration           med jadad vantulder
#> 1     Carette et al.  51 1986        Canada   92.6    NA 41.8        9 amitriptyline     4         9
#> 2     Carette et al.  52 1995        Canada   95.5    NA 43.8        8 amitriptyline     4         8
#> 3     Carette et al.  52 1995        Canada   95.5    NA 43.8        8 amitriptyline     4         8
#> 4     Carette et al.  52 1995        Canada   95.5    NA 43.8        8 amitriptyline     4         8
#> 5    Ginsberg et al.  53 1998       Belgium   87.9    NA 39.7        4    pirlindole     3         7
#> 6    Ginsberg et al.  54 1996       Belgium   83.0  92.0 46.0        8 amitriptyline     4         8
#> 7    Ginsberg et al.  54 1996       Belgium   83.0  92.0 46.0        8 amitriptyline     4         8
#> 8    Ginsberg et al.  54 1996       Belgium   83.0  92.0 46.0        8 amitriptyline     4         8
#> 9  Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6    fluoxetine     5         7
#> 10 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6    fluoxetine     5         7
#> 11 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6    fluoxetine     5         7
#> 12 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6    fluoxetine     5         7
#> 13 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6    fluoxetine     5         7
#> 14 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6 amitriptyline     5         7
#> 15 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6 amitriptyline     5         7
#> 16 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6 amitriptyline     5         7
#> 17 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6 amitriptyline     5         7
#> 18 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6 amitriptyline     5         7
#> 19   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12   moclobemide     5        10
#> 20   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12   moclobemide     5        10
#> 21   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12   moclobemide     5        10
#> 22   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12 amitriptyline     5        10
#> 23   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12 amitriptyline     5        10
#> 24   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12 amitriptyline     5        10
#> 25 Kempenaers et al.  63 1994       Belgium  100.0    NA 38.7        8 amitriptyline     3         7
#> 26 Kempenaers et al.  63 1994       Belgium  100.0    NA 38.7        8 amitriptyline     3         7
#> 27      Wolfe et al.  61 1994 United States  100.0 100.0 48.0        6    fluoxetine     3         7
#> 28      Wolfe et al.  61 1994 United States  100.0 100.0 48.0        6    fluoxetine     3         7
#> 29      Wolfe et al.  61 1994 United States  100.0 100.0 48.0        6    fluoxetine     3         7
#> 30      Wolfe et al.  61 1994 United States  100.0 100.0 48.0        6    fluoxetine     3         7
#> 31    Yavuzer et al.  62 1998        Turkey   58.3    NA 33.2        6   moclobemide     1         6
#> 32    Yavuzer et al.  62 1998        Turkey   58.3    NA 33.2        6   moclobemide     1         6
#> 33    Heymann et al.  57 2001        Brazil  100.0  65.0 53.4        8 amitriptyline     5         8
#> 34    Heymann et al.  57 2001        Brazil  100.0  65.0 53.4        8  nortiptyline     5         8
#> 35  Anderberg et al.  47 2000        Sweden  100.0    NA 48.6       16    citalopram     4         9
#> 36  Anderberg et al.  47 2000        Sweden  100.0    NA 48.6       16    citalopram     4         9
#> 37  Anderberg et al.  47 2000        Sweden  100.0    NA 48.6       16    citalopram     4         9
#> 38  Anderberg et al.  47 2000        Sweden  100.0    NA 48.6       16    citalopram     4         9
#> 39     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 40     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 41     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 42     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 43     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 44     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 45     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 46     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7
#> 47     Arnold et al.  49 2004 United States   88.5  88.5 49.9       12    duloxetine     5         8
#> 48     Arnold et al.  49 2004 United States   88.5  88.5 49.9       12    duloxetine     5         8
#> 49     Arnold et al.  49 2004 United States   88.5  88.5 49.9       12    duloxetine     5         8
#> 50     Arnold et al.  49 2004 United States   88.5  88.5 49.9       12    duloxetine     5         8
#> 51     Arnold et al.  48 2002 United States  100.0  90.0 46.0       12    fluoxetine     4         7
#> 52     Arnold et al.  48 2002 United States  100.0  90.0 46.0       12    fluoxetine     4         7
#> 53     Arnold et al.  48 2002 United States  100.0  90.0 46.0       12    fluoxetine     4         7
#> 54     Arnold et al.  48 2002 United States  100.0  90.0 46.0       12    fluoxetine     4         7
#> 55 Nørregaard et al.  58 1995       Denmark     NA    NA 48.0        8    citalopram     4         6
#> 56 Nørregaard et al.  58 1995       Denmark     NA    NA 48.0        8    citalopram     4         6
#> 57 Nørregaard et al.  58 1995       Denmark     NA    NA 48.0        8    citalopram     4         6
#> 58 Nørregaard et al.  58 1995       Denmark     NA    NA 48.0        8    citalopram     4         6
#> 59 Nørregaard et al.  58 1995       Denmark     NA    NA 48.0        8    citalopram     4         6
#> 60     Patkar et al.  59 2007 United States   94.0    NA 47.9       12    paroxetine     5         9
#> 61    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 62    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 63    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 64    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 65    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 66    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 67    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 68    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 69    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8
#> 70     Vitton et al.  60 2004 United States   97.0  47.0 84.0       12   milnacipran     3         7
#> 71     Vitton et al.  60 2004 United States   97.0  47.0 84.0       12   milnacipran     3         7
#>    tgrp cgrp outcome   type nti    mti  sdti nci    mci  sdci
#> 1    t1   c1    pain    raw  27   4.30  3.00  32   5.00  3.00
#> 2    t2   c2    pain    raw  22   5.07  3.22  22   7.13  2.41
#> 3    t2   c2 fatigue    raw  22   5.62  3.07  20   7.64  1.80
#> 4    t2   c2   sleep    raw  22   3.93  3.14  20   6.51  2.69
#> 5    t3   c3    pain    raw  33   4.85  2.11  28   6.79  1.53
#> 6    t4   c4    pain    raw  20   3.80  2.40  20   7.00  1.30
#> 7    t4   c4 fatigue    raw  20   3.80  2.50  20   5.90  2.20
#> 8    t4   c4   sleep    raw  24   2.60  3.10  22   5.10  3.00
#> 9    t5   c5    pain    raw  22   5.75  2.57  19   8.15  1.65
#> 10   t5   c5 fatigue    raw  22   6.86  2.41  19   7.37  2.51
#> 11   t5   c5   sleep    raw  22   6.66  2.66  19   7.46  2.39
#> 12   t5   c5    mood    raw  22   7.80  4.70  19   9.30  6.50
#> 13   t5   c5     qol    raw  22  47.60 19.80  19  58.50 17.10
#> 14   t6   c5    pain    raw  21   6.40  2.83  19   8.15  1.65
#> 15   t6   c5 fatigue    raw  21   6.77  2.99  19   7.37  2.51
#> 16   t6   c5   sleep    raw  21   5.70  3.48  19   7.46  2.39
#> 17   t6   c5    mood    raw  20   8.70  6.00  19   9.30  6.50
#> 18   t6   c5     qol    raw  21  52.30 22.90  19  58.50 17.10
#> 19   t7   c7    pain    raw  30   4.50  2.70  30   5.20  2.70
#> 20   t7   c7 fatigue    raw  30   4.90  2.70  30   4.60  2.60
#> 21   t7   c7   sleep    raw  30   5.80  3.00  30   4.80  2.90
#> 22   t8   c7    pain    raw  32   4.50  2.80  30   5.20  2.70
#> 23   t8   c7 fatigue    raw  32   4.70  2.80  30   4.60  2.60
#> 24   t8   c7   sleep    raw  32   3.60  2.80  30   4.80  2.90
#> 25   t9   c9    pain    raw   6   3.20  3.10   8   3.70  2.80
#> 26   t9   c9   sleep    raw   6   4.70  3.00   8   6.00  2.20
#> 27  t10  c10    pain    raw  15   1.60  0.79   9   1.60  0.79
#> 28  t10  c10 fatigue    raw  15   7.70  3.98   9   7.80  4.20
#> 29  t10  c10   sleep    raw  15   7.60  3.10   9   7.60  3.83
#> 30  t10  c10    mood    raw  15   8.30  5.86   9  13.90 10.82
#> 31  t11  c11    pain    raw  26   1.57  0.88  22   1.88  0.83
#> 32  t11  c11    mood    raw  28   5.54  5.56  25   5.36  2.68
#> 33  t12  c12     qol    raw  37  39.97 19.88  33  51.68 22.90
#> 34  t13  c12     qol    raw  36  48.78 21.84  33  51.68 22.90
#> 35  t14  c14    pain change  17  -1.00  1.86  18   0.00  2.47
#> 36  t14  c14 fatigue change  17  -0.63  3.01  18  -0.22  2.42
#> 37  t14  c14   sleep change  17  -0.59  0.62  18  -0.39  1.80
#> 38  t14  c14    mood change  17  -1.13  2.87  18  -0.33  2.14
#> 39  t15  c15    pain change 116  -2.39  2.37 118  -1.16  2.28
#> 40  t15  c15   sleep change 116  -2.67  3.12 118  -1.71  3.04
#> 41  t15  c15    mood change 111  -3.79  4.34 109  -2.24  4.70
#> 42  t15  c15     qol change 114 -16.72 16.34 115  -8.35 16.40
#> 43  t16  c15    pain change 114  -2.40  2.35 118  -1.16  2.28
#> 44  t16  c15   sleep change 114  -2.69  3.09 118  -1.71  3.04
#> 45  t16  c15    mood change 110  -2.97  4.72 109  -2.24  4.70
#> 46  t16  c15     qol change 112 -16.81 16.30 115  -8.35 16.40
#> 47  t17  c17    pain change 101  -1.98  3.01 103  -1.35  2.94
#> 48  t17  c17 fatigue change 101  -1.30  2.91 103  -0.88  2.84
#> 49  t17  c17    mood change  88  -3.32  7.97  89  -1.02  7.83
#> 50  t17  c17     qol change 101 -13.46 18.29 102  -7.93 17.47
#> 51  t18  c18    pain change  19  -2.30  2.40  18  -0.10  2.50
#> 52  t18  c18 fatigue change  19  -1.60  2.80  18   0.40  2.80
#> 53  t18  c18    mood change  19  -1.50  2.80  18   0.50  2.10
#> 54  t18  c18     qol change  19 -11.50 14.80  18  -0.40 15.00
#> 55  t19  c19    pain change  21   1.00  2.10  21   0.70  1.10
#> 56  t19  c19 fatigue change  21   0.50  2.20  21   0.10  2.00
#> 57  t19  c19   sleep change  21  -1.00  2.90  21  -0.10  2.50
#> 58  t19  c19    mood change  21  -1.00  6.10  21  -0.90  7.90
#> 59  t19  c19     qol change  21   0.00  0.40  21   0.00  0.40
#> 60  t20  c20    pain change  38 -12.20 18.50  48  -8.80 16.60
#> 61  t21  c21    pain change  79  -2.22  2.49 144  -1.43  2.52
#> 62  t21  c21 fatigue change  79  -1.79  3.91 144  -1.69  4.08
#> 63  t21  c21     qol change  79 -14.77 16.71 144 -10.42 17.52
#> 64  t22  c21    pain change 150  -1.98  2.57 144  -1.43  2.52
#> 65  t22  c21 fatigue change 150  -1.83  4.16 144  -1.69  4.08
#> 66  t22  c21     qol change 150 -12.28 17.64 144 -10.42 17.52
#> 67  t23  c21    pain change 147  -2.26  2.55 144  -1.43  2.52
#> 68  t23  c21 fatigue change 147  -2.12  4.00 144  -1.69  4.08
#> 69  t23  c21     qol change 147 -13.86 17.10 144 -10.42 17.52
#> 70  t24  c24    pain change  97  -2.30  3.00  28  -0.90  2.90
#> 71  t24  c24   sleep change  97  -1.30  3.10  28  -0.50  2.90

### load metafor package
library(metafor)

### compute the SMD values for the outcome pain
dat <- escalc(measure="SMD", m1i=mti, sd1i=sdti, n1i=nti,
                             m2i=mci, sd2i=sdci, n2i=nci,
                             data=dat, subset=outcome == "pain")
dat
#> 
#>                study ref year       country female white mage duration           med jadad vantulder 
#> 1     Carette et al.  51 1986        Canada   92.6    NA 41.8        9 amitriptyline     4         9 
#> 2     Carette et al.  52 1995        Canada   95.5    NA 43.8        8 amitriptyline     4         8 
#> 5    Ginsberg et al.  53 1998       Belgium   87.9    NA 39.7        4    pirlindole     3         7 
#> 6    Ginsberg et al.  54 1996       Belgium   83.0  92.0 46.0        8 amitriptyline     4         8 
#> 9  Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6    fluoxetine     5         7 
#> 14 Goldenberg et al.  55 1996 United States   90.0 100.0 43.2        6 amitriptyline     5         7 
#> 19   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12   moclobemide     5        10 
#> 22   Hannonen et al.  56 1998       Finland  100.0    NA 49.7       12 amitriptyline     5        10 
#> 25 Kempenaers et al.  63 1994       Belgium  100.0    NA 38.7        8 amitriptyline     3         7 
#> 27      Wolfe et al.  61 1994 United States  100.0 100.0 48.0        6    fluoxetine     3         7 
#> 31    Yavuzer et al.  62 1998        Turkey   58.3    NA 33.2        6   moclobemide     1         6 
#> 35  Anderberg et al.  47 2000        Sweden  100.0    NA 48.6       16    citalopram     4         9 
#> 39     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7 
#> 43     Arnold et al.  50 2005 United States  100.0  89.5 49.6       12    duloxetine     3         7 
#> 47     Arnold et al.  49 2004 United States   88.5  88.5 49.9       12    duloxetine     5         8 
#> 51     Arnold et al.  48 2002 United States  100.0  90.0 46.0       12    fluoxetine     4         7 
#> 55 Nørregaard et al.  58 1995       Denmark     NA    NA 48.0        8    citalopram     4         6 
#> 60     Patkar et al.  59 2007 United States   94.0    NA 47.9       12    paroxetine     5         9 
#> 61    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8 
#> 64    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8 
#> 67    Russell et al.  64 2008 United States   94.8  84.2 51.0       28    duloxetine     4         8 
#> 70     Vitton et al.  60 2004 United States   97.0  47.0 84.0       12   milnacipran     3         7 
#>    tgrp cgrp outcome   type nti    mti  sdti nci   mci  sdci      yi     vi 
#> 1    t1   c1    pain    raw  27   4.30  3.00  32  5.00  3.00 -0.2302 0.0687 
#> 2    t2   c2    pain    raw  22   5.07  3.22  22  7.13  2.41 -0.7113 0.0967 
#> 5    t3   c3    pain    raw  33   4.85  2.11  28  6.79  1.53 -1.0258 0.0746 
#> 6    t4   c4    pain    raw  20   3.80  2.40  20  7.00  1.30 -1.6250 0.1330 
#> 9    t5   c5    pain    raw  22   5.75  2.57  19  8.15  1.65 -1.0728 0.1121 
#> 14   t6   c5    pain    raw  21   6.40  2.83  19  8.15  1.65 -0.7310 0.1069 
#> 19   t7   c7    pain    raw  30   4.50  2.70  30  5.20  2.70 -0.2559 0.0672 
#> 22   t8   c7    pain    raw  32   4.50  2.80  30  5.20  2.70 -0.2512 0.0651 
#> 25   t9   c9    pain    raw   6   3.20  3.10   8  3.70  2.80 -0.1598 0.2926 
#> 27  t10  c10    pain    raw  15   1.60  0.79   9  1.60  0.79  0.0000 0.1778 
#> 31  t11  c11    pain    raw  26   1.57  0.88  22  1.88  0.83 -0.3556 0.0852 
#> 35  t14  c14    pain change  17  -1.00  1.86  18  0.00  2.47 -0.4450 0.1172 
#> 39  t15  c15    pain change 116  -2.39  2.37 118 -1.16  2.28 -0.5273 0.0177 
#> 43  t16  c15    pain change 114  -2.40  2.35 118 -1.16  2.28 -0.5340 0.0179 
#> 47  t17  c17    pain change 101  -1.98  3.01 103 -1.35  2.94 -0.2110 0.0197 
#> 51  t18  c18    pain change  19  -2.30  2.40  18 -0.10  2.50 -0.8789 0.1186 
#> 55  t19  c19    pain change  21   1.00  2.10  21  0.70  1.10  0.1756 0.0956 
#> 60  t20  c20    pain change  38 -12.20 18.50  48 -8.80 16.60 -0.1930 0.0474 
#> 61  t21  c21    pain change  79  -2.22  2.49 144 -1.43  2.52 -0.3137 0.0198 
#> 64  t22  c21    pain change 150  -1.98  2.57 144 -1.43  2.52 -0.2155 0.0137 
#> 67  t23  c21    pain change 147  -2.26  2.55 144 -1.43  2.52 -0.3265 0.0139 
#> 70  t24  c24    pain change  97  -2.30  3.00  28 -0.90  2.90 -0.4672 0.0469 
#> 

### fit a random-effects model
res <- rma(yi, vi, data=dat, method="DL", digits=2)
res
#> 
#> Random-Effects Model (k = 22; tau^2 estimator: DL)
#> 
#> tau^2 (estimated amount of total heterogeneity): 0.03 (SE = 0.03)
#> tau (square root of estimated tau^2 value):      0.19
#> I^2 (total heterogeneity / total variability):   44.97%
#> H^2 (total variability / sampling variability):  1.82
#> 
#> Test for Heterogeneity:
#> Q(df = 21) = 38.16, p-val = 0.01
#> 
#> Model Results:
#> 
#> estimate    se   zval  pval  ci.lb  ci.ub      
#>    -0.43  0.06  -6.68  <.01  -0.55  -0.30  *** 
#> 
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
predict(res)
#> 
#>   pred   se ci.lb ci.ub pi.lb pi.ub 
#>  -0.43 0.06 -0.55 -0.30 -0.81 -0.04 
#> 

### construct an approximate var-cov matrix of the SMD values accounting for
### the dependency in the estimates due to the use of shared control groups
V <- vcalc(vi, cluster=ref, grp1=tgrp, grp2=cgrp, data=dat)
V
#> 
#>         1      2      3      4      5      6      7      8      9     10     11     12     13     14 
#> 1  0.0687      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 2       . 0.0967      .      .      .      .      .      .      .      .      .      .      .      . 
#> 3       .      . 0.0746      .      .      .      .      .      .      .      .      .      .      . 
#> 4       .      .      . 0.1330      .      .      .      .      .      .      .      .      .      . 
#> 5       .      .      .      . 0.1121 0.0547      .      .      .      .      .      .      .      . 
#> 6       .      .      .      . 0.0547 0.1069      .      .      .      .      .      .      .      . 
#> 7       .      .      .      .      .      . 0.0672 0.0331      .      .      .      .      .      . 
#> 8       .      .      .      .      .      . 0.0331 0.0651      .      .      .      .      .      . 
#> 9       .      .      .      .      .      .      .      . 0.2926      .      .      .      .      . 
#> 10      .      .      .      .      .      .      .      .      . 0.1778      .      .      .      . 
#> 11      .      .      .      .      .      .      .      .      .      . 0.0852      .      .      . 
#> 12      .      .      .      .      .      .      .      .      .      .      . 0.1172      .      . 
#> 13      .      .      .      .      .      .      .      .      .      .      .      . 0.0177 0.0089 
#> 14      .      .      .      .      .      .      .      .      .      .      .      . 0.0089 0.0179 
#> 15      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 16      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 17      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 18      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 19      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 20      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 21      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#> 22      .      .      .      .      .      .      .      .      .      .      .      .      .      . 
#>        15     16     17     18     19     20     21     22 
#> 1       .      .      .      .      .      .      .      . 
#> 2       .      .      .      .      .      .      .      . 
#> 3       .      .      .      .      .      .      .      . 
#> 4       .      .      .      .      .      .      .      . 
#> 5       .      .      .      .      .      .      .      . 
#> 6       .      .      .      .      .      .      .      . 
#> 7       .      .      .      .      .      .      .      . 
#> 8       .      .      .      .      .      .      .      . 
#> 9       .      .      .      .      .      .      .      . 
#> 10      .      .      .      .      .      .      .      . 
#> 11      .      .      .      .      .      .      .      . 
#> 12      .      .      .      .      .      .      .      . 
#> 13      .      .      .      .      .      .      .      . 
#> 14      .      .      .      .      .      .      .      . 
#> 15 0.0197      .      .      .      .      .      .      . 
#> 16      . 0.1186      .      .      .      .      .      . 
#> 17      .      . 0.0956      .      .      .      .      . 
#> 18      .      .      . 0.0474      .      .      .      . 
#> 19      .      .      .      . 0.0198 0.0082 0.0083      . 
#> 20      .      .      .      . 0.0082 0.0137 0.0069      . 
#> 21      .      .      .      . 0.0083 0.0069 0.0139      . 
#> 22      .      .      .      .      .      .      . 0.0469 
#> 

### fit a multilevel random-effects model
res <- rma.mv(yi, V, random = ~ 1 | ref/tgrp, data=dat, digits=2)
res
#> 
#> Multivariate Meta-Analysis Model (k = 22; method: REML)
#> 
#> Variance Components:
#> 
#>            estim  sqrt  nlvls  fixed    factor 
#> sigma^2.1   0.06  0.24     17     no       ref 
#> sigma^2.2   0.00  0.00     22     no  ref/tgrp 
#> 
#> Test for Heterogeneity:
#> Q(df = 21) = 35.59, p-val = 0.02
#> 
#> Model Results:
#> 
#> estimate    se   zval  pval  ci.lb  ci.ub      
#>    -0.45  0.09  -5.26  <.01  -0.62  -0.28  *** 
#> 
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
predict(res)
#> 
#>   pred   se ci.lb ci.ub pi.lb pi.ub 
#>  -0.45 0.09 -0.62 -0.28 -0.95  0.05 
#> 

### use cluster-robust inference methods
robust(res, cluster=ref, clubSandwich=TRUE)
#> 
#> Multivariate Meta-Analysis Model (k = 22; method: REML)
#> 
#> Variance Components:
#> 
#>            estim  sqrt  nlvls  fixed    factor 
#> sigma^2.1   0.06  0.24     17     no       ref 
#> sigma^2.2   0.00  0.00     22     no  ref/tgrp 
#> 
#> Test for Heterogeneity:
#> Q(df = 21) = 35.59, p-val = 0.02
#> 
#> Number of estimates:   22
#> Number of clusters:    17
#> Estimates per cluster: 1-3 (mean: 1.29, median: 1)
#> 
#> Model Results:
#> 
#> estimate    se¹   tval¹     df¹  pval¹  ci.lb¹  ci.ub¹      
#>    -0.45  0.08   -5.30   13.62   <.01   -0.63   -0.27   *** 
#> 
#> ---
#> Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
#> 
#> 1) results based on cluster-robust inference (var-cov estimator: CR2,
#>    approx t-test and confidence interval, df: Satterthwaite approx)
#>