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Hay ni chung l:
xi = M + ei
Tt nhin ei c th <0 hay >0. Nu M v ei c lp vi nhau (tc khng c tng quan
g vi nhau) th phng sai ca xi (gi l var[xi ] ) c th vit nh sau:
var[xi ] = var[M ] + var[ei ] = 0 + se2
xi = mi + ei
Trong :
Thnh ra:
mi = M + i
xi = M + i + ei
Nh ta thy qua cng thc ny, s2 phn nh dao ng gia cc nghin cu (betweenstudy variation), cn se2 phn nh dao ng trong mi nghin cu (within-study
variation). Mc ch ca phn tch tng hp nh hng bin thin l c tnh M, se2
v s2 .
Ni tm li, Phn tch tng hp nh hng bt bin v Phn tch tng hp nh
hng bin thin ch khc nhau phng sai. Trong khi phn tch tng hp bt bin
xem s2 = 0, th phn tch tng hp bin thin t yu cu phi c tnh s2 . Tt nhin,
nu s2 = 0 th kt qu ca hai phn tch ny ging nhau. Trong bi ny ti s tp trung
vo cch phn tch tng hp nh hng bt bin.
Cng nh phn tch thng k cho tng nghin cu ring l ty thuc vo loi tiu
ch (nh l bin s lin tc continuous variables hay bin s nh phn dichotomous
variables), phng php phn tch tng hp cng ty thuc vo cc tiu ch ca nghin
cu. Ti s ln lc m t hai phng php chnh cho hai loi bin s lin tc v nh
phn.
9
Tng cng
60
548
30
27
52
610
23
20
di = LOS1i LOS2i
Phng sai ca di (ti s k hiu l si2 ) c c tnh bng mt cng thc chun da vo
lch chun v s i tng trong tng nghin cu. Vi mi nghin cu i (i = 1, 2, 3,
, 9), chng ta c:
si2 =
1
1
N + N
2i
1i
N1i + N 2i 2
d1 = 75 55 = 20
v phng sai ca d1:
2
1
155 + 156 2
1
1
+
= 40.59
155 156
Bng 1a. khc bit v thi gian gia hai nhm v khong tin cy 95%
Nghin cu (i)
1
2
3
4
5
6
7
8
9
di
20
2
55
71
4
-1
-11
10
-7
si2
40.6
2.0
15.3
150.2
20.2
1.2
95.4
8.0
20.7
si
6.37
1.43
3.91
12.26
4.49
1.11
9.77
2.83
4.55
di-1.96*si
di+1.96*si
7.51
-0.80
47.34
46.98
-4.81
-3.17
-30.14
4.45
-15.92
32.49
4.80
62.66
95.02
12.81
1.17
8.14
15.55
1.92
Wi = 1 / si2
Chng hn nh vi nghin cu 1, chng ta c: W1 =
1
= 0.0246
40.59
1
2
3
4
5
6
7
8
9
Tng s
di
20
2
55
71
4
-1
-11
10
-7
Wi
si2
40.6
2.0
15.3
150.2
20.2
1.2
95.4
8.0
20.7
0.0246
0.4886
0.0654
0.0067
0.0495
0.8173
0.0105
0.1245
0.0483
1.6354
Do , tnh trung bnh d cho tng s nghin cu, chng ta phi xem xt n trng s
Wi. Vi mi di v Wi chng ta c th tnh tr s trung bnh trng s (weighted mean)
theo phng php chun nh sau:
9
d=
W d
i =1
9
W
i =1
Sai s chun (standard error, SE) ca d, do l: SE(d) = sd . Theo l thuyt phn phi
chun (Normal distribution), khong tin cy 95% (95% confidence interval, 95%CI) c
th c c tnh nh sau:
95%CI ca d = d 1.96 ( sd )
tnh d chng ta cn thm mt ct na: l ct Wi d i . Chng hn nh vi nghin cu
1, chng ta c W1d1 = 0,0246 20 = 0,4928 . Tip tc nh th, chng ta c thm mt ct.
Bng 1c. Tnh ton tr s trung bnh
Nghin cu
di
1
2
3
4
5
6
7
8
9
Tng s
si2
40.6
2.0
15.3
150.2
20.2
1.2
95.4
8.0
20.7
20
2
55
71
4
-1
-11
10
-7
Wi
0.0246
0.4886
0.0654
0.0067
0.0495
0.8173
0.0105
0.1245
0.0483
1.6354
Wi d i
0.4928
0.9771
3.5993
0.4726
0.1981
-0.8173
-0.1153
1.2450
-0.3383
5.7140
d=
W d
i =1
9
W
i =1
1
= 0.61 .
1.6345
Khong tin cy 95% (95% confidence interval hay 95%CI) c th c c tnh nh sau:
3.49 1,96*0.782 = 1.96 n 5.02.
n y, chng ta c th ni rng, tnh trung bnh, thi gian nm vin ti cc bnh vin
a khoa di hn cc bnh vin chuyn khoa 3.49 ngy v 95% khong tin cy l t 1.96
ngy n 5.02 ngy.
Bc 5: c tnh ch s ng nht (homogeneity) v bt ng nht
(heterogeneity) gia cc nghin cu [3]. Trong thc t, y l ch s o lng khc
bit gia mi nghin cu v tr s trung bnh trng s. Ch s ng nht (index of
homogeneity) c tnh theo cng thc sau y:
k
Q = Wi (d i d )
i =1
Q (k 1)
Q
Trong v d trn, c tnh Q v I2, chng ta cn tnh Wi (d i d ) cho tng nghin cu.
Chng hn nh, vi nghin cu 1:
2
di
si2
1
2
20
2
40.6
2.0
Wi
0.0246
0.4886
Wi (d i d )
0.4928
6.7129
0.9771
1.0903
Wi d i
10
3
4
5
6
7
8
9
Tng s
55
71
4
-1
-11
10
-7
15.3
150.2
20.2
1.2
95.4
8.0
20.7
0.0654
0.0067
0.0495
0.8173
0.0105
0.1245
0.0483
1.6354
3.5993
0.4726
0.1981
-0.8173
-0.1153
1.2450
-0.3383
5.7140
173.6080
30.3356
0.0127
16.5054
2.2026
5.2701
5.3215
241.05
Sau khi c tnh Wi (d i d ) cho tng nghin cu, chng ta cng li s ny (xem ct
sau cng) v chnh l Q :
2
Q = Wi (d i d ) = 241.05
2
i =1
T , I2 c th c tnh nh sau:
I2 =
241.05 8
= 0.966
241.05
1
sdi
11
Ni cch khc, biu funnel biu din precision vi di. Chng hn nh vi nghin cu
1, chng ta c: precision = 1 / 40,6 = 0,157 . Tnh cho tng nghin cu, chng ta c
dng bng thng k sau v biu funnel nh sau:
Bng 1e. c tnh publication bias
Nghin cu
1
2
3
4
5
6
7
8
9
di
20
2
55
71
4
-1
-11
10
-7
si2
40.6
2.0
15.3
150.2
20.2
1.2
95.4
8.0
20.7
1/si
0.1570
0.6990
0.2558
0.0816
0.2225
0.9041
0.1024
0.3528
0.2198
12
di
Ni
13
1
2
3
4
5
6
7
8
9
20
2
55
71
4
-1
-11
10
-7
311
63
146
36
21
109
67
293
112
phn tch tng hp bng R chng ta phi nhp package meta vo mi trng
vn hnh ca R (vi iu kin, tt nhin, l bn c ti v ci t meta vo R).
> library(meta)
14
S dng hm
95%-CI
z p.value
[ -4.9626; -1.9646] -4.5286 < 0.0001
[-24.0299; -3.9336] -2.7272
0.0064
Quantifying heterogeneity:
tau^2 = 205.4094; H = 5.46 [4.54; 6.58]; I^2 = 96.7% [95.2%; 97.7%]
Test of heterogeneity:
Q d.f. p.value
238.92
8 < 0.0001
Method: Inverse variance method
15
-100
-80
-60
-40
-20
Weighted mean difference
20
16
Beta-blocker
N1
T vong (d1)
25
5
9
1
194
23
25
1
105
4
320
53
33
3
261
12
133
6
232
2
1327
156
1990
145
214
8
4879
420
N2
25
16
189
25
34
321
16
84
145
134
1320
2001
212
4516
Placebo
T vong (d2)
6
2
21
2
2
67
2
13
11
5
228
217
17
612
N: s bnh nhn nghin cu; T vong: s bnh nhn cht trong thi gian theo di.
17
RR =
p1
p2
5
8
= 0,20 v p2 =
= 0,24 .
25
25
0,20
= 0,833 . Tnh ton tng t cho
0,24
cc nghin cu cn li, chng ta s c mt bng nh sau:
Nghin cu (i)
1
2
3
4
5
6
7
8
9
10
11
12
13
T l t vong
nhm BB (p1)
0.200
0.111
0.119
0.040
0.038
0.166
0.091
0.046
0.045
0.009
0.118
0.073
0.037
T l t vong
nhm placebo
(p2)
0.240
0.125
0.111
0.080
0.059
0.209
0.125
0.155
0.076
0.037
0.173
0.108
0.080
T s nguy
c (RR)
0.833
0.889
1.067
0.500
0.648
0.794
0.727
0.297
0.595
0.231
0.681
0.672
0.466
1
1
1
1
d1 N1 d1 d 2 N 2 d 2
18
1
1
1
1
d1 N 1 d1 d 2 N 2 d 2
1
1
1
1
+
= 0.264
5 25 5 6 25 6
V sai s chun:
Nghin
cu (i)
1
2
3
4
5
6
7
8
T s nguy
c (RR)
Log[RR]
Var[logRR]
0.200
0.111
0.119
0.040
0.038
0.166
0.091
0.046
-0.182
-0.118
0.065
-0.693
-0.434
-0.231
-0.318
-1.214
0.264
1.304
0.079
1.415
0.709
0.026
0.729
0.142
Phn cao
95% CI
ca RR
2.28
8.33
1.85
5.15
3.37
1.09
3.87
0.62
19
9
10
11
12
13
0.045
0.009
0.118
0.073
0.037
-0.520
-1.465
-0.385
-0.398
-0.763
0.242
0.688
0.009
0.010
0.174
0.492
0.829
0.095
0.102
0.417
0.23
0.05
0.56
0.55
0.21
1.56
1.17
0.82
0.82
1.06
20
Wi =
1
var[log RRi ]
W log[RR ]
i
log wRR =
Vi phng sai:
Var[logwRR] =
v sai s chun:
SE [log wRR ] =
1
= 3.79
0, 264
Nghin cu (i)
1
2
3
4
5
6
Log[RR]
-0.182
-0.118
0.065
-0.693
-0.434
-0.231
Var[logRR]
0.264
1.304
0.079
1.415
0.709
0.026
Wi Wilog[RRi]
3.79
-0.69
0.77
-0.09
12.61
0.82
0.71
-0.49
1.41
-0.61
38.30
-8.86
21
7
8
9
10
11
12
13
Tng s
-0.318
-1.214
-0.520
-1.465
-0.385
-0.398
-0.763
0.729
0.142
0.242
0.688
0.009
0.010
0.174
1.37
7.03
4.13
1.45
110.78
96.13
5.75
284.24
-0.44
-8.54
-2.15
-2.13
-42.63
-38.23
-4.39
-108.42
Chng ta c:
W log[RR ]
i
log wRR =
108, 42
= 0.38
284, 24
Vi phng sai:
1
= 0.0035
284.24
v sai s chun:
SE [ log wRR ] =
= 0.0035 = 0.06
22
c tnh ch s I2. chng ta cn tnh Wi (log RRi log wRR ) cho mi nghin cu.
Chng hn nh vi nghin cu 1. chng ta c:
2
Nghin cu (i)
1
2
3
4
5
6
7
8
9
10
11
12
13
Tng s
Log[RRi]
-0.182
-0.118
0.065
-0.693
-0.434
-0.231
-0.318
-1.214
-0.520
-1.465
-0.385
-0.398
-0.763
V d 2 c k = 13 nghin cu. Do .
k
i =1
V.
I2 =
Q (k 1) 11.18 12
=
= 0.16
Q
11.18
23
Log[RRi]
-0.182
-0.118
0.065
-0.693
-0.434
-0.231
-0.318
-1.214
-0.520
-1.465
-0.385
-0.398
-0.763
Ni
50
25
383
50
139
641
49
345
278
366
2647
3991
426
24
# S liu t v d 2
n1
d1
n2
d2
<<<<-
c(25.9.194.25.105.320.33.261.133.232.1327.1990.214)
c(5.1.23.1.4.53.3.12.6.2.156.145.8)
c(25.16.189.25.34.321.16.84.145.134.1320.2001.212)
c(6.2.21.2.2.67.2.13.11.5.228.217.17)
# To mt dataframe ly tn l bb
bb <- data.frame(n1.d1.n2.d2)
25
7
8
9
10
11
12
13
0.7273
0.2971
0.5947
0.2310
0.6806
0.6719
0.4662
[0.1346;
[0.1410;
[0.2262;
[0.0454;
[0.5635;
[0.5496;
[0.2056;
3.9282]
0.6258]
1.5632]
1.1744]
0.8221]
0.8214]
1.0570]
0.49
2.49
1.48
0.52
38.81
34.31
2.07
0.49
2.49
1.48
0.52
38.81
34.31
2.07
95%-CI
z p.value
[0.6064; 0.7672] -6.3741 < 0.0001
[0.6064; 0.7672] -6.3741 < 0.0001
Quantifying heterogeneity:
tau^2 = 0; H = 1 [1; 1.45]; I^2 = 0% [0%; 52.6%]
Test of heterogeneity:
Q d.f. p.value
11
12
0.5292
Method: Inverse variance method
1
2
3
4
5
6
7
8
9
10
11
12
13
0.05
0.10
0.20
0.50
1.00
Relative Risk
2.00
5.00
10.00
26
***
Thc ra. trong khoa hc ni chung. chng ta c mt truyn thng lu i v
vic duyt xt bng chng nghin cu (review). duyt xt kin thc hin hnh. Nhng
cc duyt xt nh th thng mang tnh nh cht (qualitative review). v v tnh nh
cht. chng ta kh m bit chnh xc c nhng khc bit mang tnh nh lng gia
cc nghin cu. Phn tch tng hp cung cp cho chng ta mt phng tin nh lng
h thng bng chng. Vi phn tch tng hp. chng ta c c hi :
Educational
[2] Normand SL. Meta-analysis: formulating. evaluating. combining. and reporting. Stat
Med. 1999;18(3):321-59.
[3] Higgins JPT. Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med.
2002;21:1539-1558
27
28
i vi cc bin s nh phn
Nhm 1 (s mu. s s kin): n1i . x1i ; i =
1. 2. 3. . k
Nhm 2 (s mu. s s kin): n2i . x2i ; i =
1. 2. 3. . k
nh hng (effect size. ES) tnh bng t
s nguy c RR:
x x
RRi = 2i 1i
n2i n1i
Bin chuyn sang logarithm:
i = log(RRi )
Phng sai ca d i :
Phng sai ca i :
1
1
1
1
s2i =
(n1i 1)s
1
+ (n2i 1)s
1
+
n1i + n2i 2
n1i n2i
Sai s (standard error) ca d i :
2
1i
sdi2 =
2
2i
sdi = sdi2
Sai s ca i :
1
1
1
1
s =
1
sdi2
c s nh hng chung:
Trng s: Wi =
k
i =1
i =1
1
s2i
c s nh hng chung:
Trng s: Wi =
k
i =1
i =1
d= Wi d i / Wi
= Wi i / Wi
Phng sai ca d:
Phng sai ca :
s 2 = 1 / Wi
s 2 = 1 / Wi
i =1
i =1
Q = Wi (d i d )
Q = Wi ( i )
Index of heterogeneity:
Q (k 1)
I2 =
Q
Xem xt publication bias: Phn tch hi qui
tuyn tnh: di = a + b*Ni . (Ni l tng s
mu ca nghin cu i). Xem ngha thng
k ca b.
Index of heterogeneity:
Q (k 1)
I2 =
Q
Xem xt publication bias: Phn tch hi qui
tuyn tnh: = a + b*Ni . (Ni l tng s
mu ca nghin cu i). Xem ngha thng
k ca b.
i =1
i =1
29
Q (k 1)
2
= max 0,
k
2
Wi
k
i =1
Wi k
i =1
Wi
i =1
Q (k 1)
2 = max 0,
k
2
Wi
k
i =1
Wi k
i =1
Wi
i =1
30