14

Phn tch tng hp

ng b ta vn thng ni Mt cy lm chng nn non, ba cy chm li ln hn
ni cao cao tinh thn hp lc, on kt nhm hon tt mt cng vic quan trng
cn n nhiu ngi. Trong nghin cu khoa hc ni chung v y hc ni ring, nhiu khi
chng ta cn phi xem xt nhiu kt qu nghin cu t nhiu ngun khc nhau gii
quyt mt vn c th.

14.1 Nhu cu cho phn tch tng hp

Trong my nm gn y, trong nghin cu khoa hc xut hin kh nhiu nghin
cu di danh mc meta-analysis, m ti tm dch l phn tch tng hp. Vy phn
tch tng hp l g, mc ch l g, v cch tin hnh ra sao l nhng cu hi m rt
nhiu bn c mun bit. Trong bi ny ti s m t s qua vi khi nim v cch tin
hnh mt phn tch tng hp, vi hi vng bn c c th t mnh lm mt phn tch m
khng cn n cc phn mm t tin.
Ngun gc v tng tng hp d liu khi u t th k 17, ch chng phi l
mt tng mi. Thi , cc nh thin vn hc ngh rng cn phi h thng ha d liu
t nhiu ngun c th i n mt quyt nh chnh xc v hp l hn cc nghin cu
ring l. Nhng phng php phn tch tng hp hin i phi ni l bt u t hn na
th k trc trong ngnh tm l hc. Nm 1952, nh tm l hc tr danh Hans J. Eysenck
tuyn b rng tm l tr liu (psychotherapy) chng c hiu qu g c. Hn hai mi nm
sau, nm 1976, Gene V. Glass, mt nh tm l hc ngi M, mun chng minh rng
Eysenck sai, nn ng tm cch thu thp d liu ca hn 375 nghin cu v tm l tr liu
trong qu kh, v tin hnh tng hp chng bng mt phng php m ng t tn l
meta-analysis [1]. Qua phng php phn tch ny, Glass tuyn b rng tm l tr liu
c hiu qu v gip ch cho bnh nhn.
Phn tch tng hp hay meta-analysis t c cc b mn khoa hc khc,
nht l y hc, ng dng gii quyt cc vn nh hiu qu ca thuc trong vic iu
tr bnh nhn. Cho n nay, cc phng php phn tch tng hp pht trin mt bc
di, v tr thnh mt phng php chun thm nh cc vn gai gc, cc vn m
s nht tr gia cc nh khoa hc vn cha t c. C ngi xem phn tch tng hp
c th cung cp mt cu tr li sau cng cho mt cu hi y hc. Ngi vit bi ny
khng lc quan v t tin nh th, nhng vn cho rng phn tch tng hp l mt phng
php rt c ch cho chng ta gii quyt nhng vn cn trong vng tranh ci. Phn tch
tng hp cng c th gip cho chng ta nhn ra nhng lnh vc no cn phi nghin cu
thm hay cn thm bng chng.
Kt qu ca mi nghin cu n l thng c nh gi hoc l tch cc (tc
l, chng hn nh, thut iu tr c hiu qu), hoc l tiu cc (tc l thut iu tr
khng c hiu qu), v s nh gi ny da vo tr s P. Thut ng ting Anh gi qui
1

trnh l significance testing th nghim ngha thng k. Nhng ngha thng k

ty thuc vo s mu c chn trong nghin cu, v mt kt qu tiu cc khng c
ngha l gi thit ca nghin cu sai, m c th l tn hiu cho thy s lng mu cha
y i n mt kt lun ng tin cy. Ci logic ca phn tch tng hp, do , l
chuyn hng t significance testing sang c tnh effect size - mc nh hng. Cu
tr li m phn tch tng hp mun a ra khng ch n gin l c hay khng c ngha
thng k (significant hay insignificant) m l mc nh hng bao nhiu, c ng
chng ta quan tm, c thch hp chng ta ng dng vo thc t lm sng trong vic
chm sc bnh nhn.

14.2 Fixed-effects v Random-effects

Hai thut ng m bn c thng gp trong cc phn tch tng hp l fixedeffects (tm dch l nh hng bt bin) v random-effects (nh hng bin thin).
hiu hai thut ng ny ti s a ra mt v d tng i n gin. Hy tng tng
chng ta mun c tnh chiu cao ca ngi Vit Nam trong tui trng thnh (18
tui tr ln). Chng ta c th tin hnh 100 nghin cu ti nhiu a im khc nhau trn
ton quc; mi nghin cu chn mu (samples) mt cch ngu nhin t 10 ngi n vi
chc ngn ngi; v c mi nghin cu chng ta tnh ton chiu cao trung bnh. Nh
vy, chng ta c 100 s trung bnh, v chc chn nhng con s ny khng ging nhau:
mt s nghin cu c chiu cao trung bnh thp, cao hay trung bnh. Phn tch tng
hp l nhm mc ch s dng 100 s trung bnh c tnh chiu cao cho ton th
ngi Vit. C hai cch c tnh: fixed-effects meta-analysis (phn tch tng hp nh
hng bt bin) v random-effects meta-analysis (phn tch tng hp nh hng bt bin)
[2].
Phn tch tng hp nh hng bt bin xem s khc bit gia 100 con s trung
bnh l do cc yu t ngu nhin lin quan n mi nghin cu (cn gi l withinstudy variance) gy nn. Ci gi nh ng sau cch nhn thc ny l: nu 100 nghin
cu u c tin hnh y chang nhau (nh c cng s lng i tng, cng tui,
cng t l gii tnh, cng ch dinh dng, v.v) th s khng c s khc bit gia cc
s trung bnh.
Nu chng ta gi s trung bnh ca 100 nghin cu l x1 , x2 ,..., x100 , quan im
ca phn tch tng hp nh hng bt bin cho rng mi xi l mt bin s gm hai phn:
mt phn phn nh s trung ca ton b qun th dn s (tm gi l M), v phn cn li
(khc bit gia xi v M l mt bin s ei . Ni cch khc:
x1 = M + e1
x2 = M + e2
.
x100 = M + e100

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

Ch var[M] = 0 v M l mt hng s bt bin, se2 l phng sai ca ei . Mc ch ca

phn tch tng hp l c tnh M v se2 .
Phn tch tng hp nh hng bin thin xem mc khc bit (cn gi l
variance hay phng sai) gia cc s trung bnh l do hai nhm yu t gy nn: cc yu
t lin quan n mi nghin cu (within-study variance) v cc yu t gia cc nghin
cu (between-study variance). Cc yu t khc bit gia cc nghin cu nh a im,
tui, gii tnh, dinh dng, v.v cn phi c xem xt v phn tch. Ni cch khc,
phn tch tng hp nh hng bin thin i xa hn phn tch tng hp nh hng bt bin
mt bc bng cch xem xt n nhng khc bit gia cc nghin cu. Do , kt qu t
phn tch tng hp nh hng bin thin thng bo th hn cc phn tch tng hp
nh hng bt bin.
Quan im ca phn tch tng hp nh hng bin thin cho rng mi nghin cu
c mt gi tr trung bnh c bit phi c tnh, gi l mi . Do , xi l mt bin s gm
hai phn: mt phn phn nh s trung ca qun th m mu c chn ( mi , ch y
c ch t i ch mt nghin cu ring l i), v phn cn li (khc bit gia xi v mi l
mt bin s ei . Ngoi ra, phn tch tng hp nh hng bin thin cn pht biu rng mi
dao ng chung quanh s tng trung bnh M bng mt bin ngu nhin i . Ni cch
khc:

xi = mi + ei
Trong :

Thnh ra:

mi = M + i
xi = M + i + ei

V phng sai ca xi by gi c hai thnh phn:

var[xi ] = var[M ] + var[ i ] + var[ei ] = 0 + s2 + se2

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.

14.3 Qui trnh ca mt phn tch tng hp

Cng nh bt c nghin cu no, mt phn tch tng hp c tin hnh qua cc
cng on nh: thu thp d liu, kim tra d liu, phn tch d liu, v kim tra kt qu
phn tch.

Bc th nht: s dng h thng th vin y khoa PubMed hay mt h thng th

vin khoa hc ca chuyn ngnh tm nhng bi bo lin quan n vn cn
nghin cu. Bi v c nhiu nghin cu, v l do no (nh kt qu tiu cc
chng hn), khng c cng b, cho nn nh nghin cu c khi cng cn phi
thm vo cc nghin cu . Vic lm ny tuy ni th d, nhng trong thc t
khng d dng cht no!

Bc th hai: r sot xem trong s cc nghin cu c truy tm , c bao nhiu

t cc tiu chun c ra. Cc tiu chun ny c th l i tng bnh
nhn, tnh trng bnh, tui, gii tnh, tiu ch, v. Chng hn nh trong s
hng trm nghin cu v nh hng ca viatmin D n long xng, c th ch
vi chc nghin cu t tiu chun nh i tng phi l ph n sau thi mn
kinh, mt xng thp, phi l nghin cu lm sng i chng ngu nhin
(randomized controlled clinical trials - RCT), tiu ch phi l gy xng i,
v.v (Nhng tiu chun ny phi c ra trc khi tin hnh nghin cu).

Bc th ba: chit s liu v d kin (data extraction). Sau khi xc nh c

i tng nghin cu, bc k tip l phi ln k hoch chit s liu t cc nghin
cu . Chng hn nh nu l cc nghin cu RCT, chng ta phi tm cho c
s liu cho hai nhm can thip v i chng. C khi cc s liu ny khng c
cng b hay trnh by trong bi bo, v trong trng hp , nh nghin cu phi
trc tip lin lc vi tc gi tm s liu. Mt bng tm lc kt qu nghin cu
c th tng t nh Bng 1 di y.

Bc th t: tin hnh phn tch thng k. Trong bc ny, mc ch l c tnh

mc nh hng chung cho tt c nghin cu v dao ng ca nh hng
. Trong bi ny, ti s gii thch c th cch lm.

Bc th nm: xem xt cc kt qu phn tch, v tnh ton thm mt s ch tiu

khc nh gi tin cy ca kt qu phn tch.

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.

14.4 Phn tch tng hp nh hng bt bin cho mt tiu

ch lin tc (Fixed-effects meta-analysis for a continuous
outcome).
14.4.1 Phn tch tng hp bng tnh ton th cng
V d 1. Thi gian nm vin iu tr cc bnh nhn t qu l mt tiu ch
quan trng trong vic vch nh chnh sch ti chnh. Cc nh nghin cu mun bit s
khc bit v thi gian nm vin gia hai nhm bnh vin chuyn khoa v bnh vin a
khoa. Cc nh nghin cu ra sot v thu thp s liu t 9 nghin cu nh sau (xem Bng
1). Mt s nghin cu cho thy thi gian nm vin trong cc bnh vin chuyn khoa
ngn hn cc bnh vin a khoa (nh nghin cu 1, 2, 3, 4, 5, 8), mt s nghin cu khc
cho thy ngc li (nh nghin cu 7 v 9). Vn t ra l cc s liu ny c ph hp
vi gi thit bnh nhn cc bnh vin a khoa thng c thi gian nm vin ngn hn cc
bnh vin a khoa hay khng. Chng ta c th tr li cu hi ny qua cc bc sau y:
Bc 1: tm lc d liu trong mt bng thng k nh sau:
Bng 1. Thi gian nm bnh vin ca cc bnh nhn t qu trong hai nhm bnh
vin chuyn khoa v a khoa
Nghin
cu (i)
1
2
3
4
5
6
7
8

Bnh vin chuyn khoa

LOS1i
SD1i
N1i
155
55
47
31
27
7
75
64
17
18
66
20
8
14
8
57
19
7
34
52
45
110
21
16

Bnh vin a khoa

N2i
LOS2i
SD2i
156
75
64
32
29
4
71
119
29
18
137
48
13
18
11
52
18
4
33
41
34
183
31
27

9
Tng cng

60
548

30

27

52
610

23

20

Ch thch: Trong bng ny, i l ch s ch mi nghin cu, i=1,2,,9. N1 v N2 l s bnh nhn

nghin cu cho tng nhm bnh vin; LOS1 v LOS2 (length of stay): thi gian trung bnh nm
vin (tnh bng ngy); SD1 v SD2: lch chun (standard deviation) ca thi gian nm vin.

Bc 2: c tnh mc khc bit trung bnh v phng sai (variance) cho

tng nghin cu. Mi nghin cu c tnh mt nh hng, hay ni chnh xc hn l
khc bit v thi gian nm vin k hiu, v ti s t k hiu l di gia hai nhm bnh
vin. Ch s nh hng ny ch n gin l:

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 =

(N1i 1)SD12i + (N 2i 1)SD22i

1
1
N + N
2i
1i

N1i + N 2i 2

Chng hn nh vi nghin cu 1, chng ta c:

d1 = 75 55 = 20
v phng sai ca d1:

(155 1)( 47 ) + (156 1)( 64 )

=
2

2
1

155 + 156 2

1
1
+

= 40.59
155 156

hay lch chun: s1 = 40.59 = 6.37

Vi lch chun si chng ta c th c tnh khong tin cy 95% (95% confidence
interval hay 95%CI) cho di bng l thuyt phn phi chun (Normal distribution). Cn
nhc li rng, nu mt bin s tun theo nh lut phn phi chun th 95% cc gi tr ca
bin s s nm trong khong 1,96 ln lch chun. Do , khong tin cy 95% cho
mc khc bit ca nghin cu 1 l:
n

di - 1.96*si = 20 1.96*6.37 = 7.71 ngy

di + 1.96*si = 20 + 1.96*6.37 = 32.49 ngy

Tip tc tnh nh th cho cc nghin cu khc, chng ta s c thm bn ct trong bng

sau y:

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

n y chng ta c th th hin mc nh hng di v khong tin cy 95% trong mt

biu c tn l forest plot nh sau:

Biu forest th hin gi tr ca di v khong tin cy 95%. Mc nh hng di

ghi nhn t nghin cu 5, 7 v 9 c xem l khng c ngha thng k, v khong
tin cy 95% vt qua ct mc 0.

Bc 3: c tnh trng s (weight) cho mi nghin cu. Trng s (Wi) thc

ra ch l s o ca phng sai si2 ,

Wi = 1 / si2
Chng hn nh vi nghin cu 1, chng ta c: W1 =

1
= 0.0246
40.59

V chng ta c thm mt ct mi cho bng trn nh sau:

Bng 1b. Trng s (weight) cho tng nghin cu
Nghin cu

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

Bc 4: c tnh tr s trung bnh ca d cho tt c cc nghin cu. Chng ta

c th n gin tnh trung bnh d bng cch cng tt c di v chia cho 9, nhng cch tnh
nh th khng khch quan, bi v mi gi tr di c mt phng sai v trng s (Wi) c
bit. Chng hn nh nghin cu 4, v phng sai cao nht (150.2), chng t rng nghin
cu ny c s i tng t hay dao ng rt cao, v dao ng cao c ngha l chng
ta khng t nim tin cy vo cao c. Chnh v th m trng s cho nghin cu
ny rt thp, ch 0.0067. Ngc li, nghin cu 6 c trng s cao v dao ng thp
(phng sai thp) v c tnh nh hng ca nghin cu ny c trng lng hn cc
nghin khc trong nhm.

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

Bt c mt c tnh thng k (estimate) no cng phi c mt phng sai. V trong

trng hp d, phng sai (ti s k hiu l sd2 ) ch n gin l s o ca tng trng s
W i:
1
sd2 = 9
Wi
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

Sau , cng tt c Wi v Wi d i (trong hng Tng s ca bng trn). Nh vy, tr s

trung bnh trng s ca d l:
9

d=

W d
i =1
9

W
i =1

0.4928 + 0.9771 + ... 0.3383 5.7140

=
= 3.49 .
0.0246 + 0.4886 + ... + 0.0483 1.6354

V phng sai ca d l: sd2 =

1
= 0.61 .
1.6345

Ni cch khc, sai s chun (standard error) ca d l: sd = 0.61 = 0.782 .

9

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

y, k l s nghin cu (trong v d trn k = 9). Theo l thuyt xc sut, Q c phn

phi theo lut Chi-square vi bc t do (degrees of freedom df) l k-1 (tc l k21 ).
Ni cch khc, nu Q ln hn k21 th l tn hiu cho thy s bt ng nht gia cc
nghin cu c ngha thng k (significant).
Nhiu nghin cu trong thi gian qua ch ra rng Q thng khng pht hin c
s bt ng nht mt cch nht qun, cho nn ngy nay t ai dng ch s ny trong phn
tch tng hp. Mt ch s khc thay th Q c tn l index of heterogeneity (I2)m ti
tm dch l ch s bt ng nht, nhng s gi cch vit I2. Ch s ny c nh ngha
nh sau:
I2 =

Q (k 1)
Q

I2 c gi tr t m n 1. Nu I2 < 0, th chng ta s cho n l 0; nu I2 gn bng 1 th

l du hiu cho thy c s bt ng nht gia cc nghin cu.

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

Wi (d i d ) = 0,0246*(20 3.49)2 = 6,7129

2

Bng 1d. Tnh ton cc ch s ng nht v bt ng nht

Nghin cu

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

Ch s bt ng nht I2 rt cao, cho thy dao ng v di gia cc nghin cu rt cao.

iu ny chng ta c th thy c ch qua nhn vo ct s 2 trong bng thng k trn.
Bc 6: nh gi kh nng publication bias [4]. Publication bias (tm dch:
trong thin v) l mt khi nim tng i mi c th gii thch bng tnh hung thc t
sau y. Chng ta bit rng khi mt nghin cu cho ra kt qu negative (kt qu tiu
cc, tc l khng pht hin mt nh hng hay mt mi lin h c ngha thng k)
cng trnh nghin cu rt kh c c hi c cng b trn cc tp san, bi v gii ch
bt tp san ni chung khng thch in nhng bi nh th. Ngc li, mt nghin cu vi
mt kt qu tch cc (tc c ngha thng k) th nghin cu c kh nng xut hin
trn cc tp san khoa hc cao hn l cc nghin cu vi kt qu tiu cc. Th nhng
phn ln nhng phn tch tng hp li da vo cc kt qu cng b trn cc tp san
khoa hc. Do , c tnh ca mt phn tch tng hp c kh nng thiu khch quan, v
cha xem xt y n cc nghin cu tiu cc cha bao gi cng b.

Mt s nh nghin cu ngh dng biu funnel (cn gi l funnel plot)

kim tra kh nng publication bias. Biu funnel c th hin bng cch v chnh
xc precision (trc tung, y-axis) vi c tnh mc nh hng cho tng nghin cu.
y precision c nh ngha l s o ca sai s chun (standard error):
precision =

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

Biu funnel (biu phu): trc tung l precision v trc honh l d.

Biu ny cho thy phn ln cc nghin cu c kt qu thi gian nm
vin trong cc bnh vin a khoa thng lu hn cc bnh vin chuyn
khoa.

12

Ci logic ng sau biu funnel l nu cc cng trnh nghin cu ln (tc c

precision cao) c kh nng c cng b cao, th s lng nghin cu vi kt qu tch
cc s nhiu hn s lng nghin cu nh hay vi kt qu tiu cc trong cc tp san. V
nu iu ny xy ra, th biu funnel s th hin mt s thiu cn i (asymmetry). Ni
cch khc, s thiu cn i ca mt biu funnel l du hiu cho thy c vn v
publication bias. Nhng vn t ra l publication bias c ngha thng k hay
khng? Biu funnel khng th tr li cu hi ny, chng ta cn n cc phng php
phn tch nh lng nghim chnh hn.
Nghim ton Egger

Vi nm gn y c kin cho rng biu funnel rt kh din dch, v c th

gy nn ng nhn v publication bias [5-6]. Tht vy, mt s tp san y hc c chnh sch
khuyn khch cc nh nghin cu tm mt phng php khc nh gi publication bias
thay v dng biu funnel.
Mt trong nhng phng php l nghim ton Egger (cn gi l Egger's test).
Vi phng php ny, chng ta m hnh rng SND = a + b x precision, trong SND
d
c c tnh bng cch ly d chia cho sai s chun ca d, tc l: SNDi = i , a v b l
sdi
hai thng s phi c tnh t m hnh hi qui ng thng . y, a cung cp cho
chng ta mt c s v tnh trng thiu cn i ca biu funnel: a>0 c ngha l xu
hng nghin cu cng c qui m ln cng c c s v nh hng vi s chnh xc
cao.
Trong v d trn, chng ta c th dng mt phn mm phn tch thng k (nh
SAS hay R) c tnh a v b nh sau:
SNDi = 4.20 + -4.17084*precisioni
Kt qu c s a = 4.20 tuy l >0 nhng khng c ngha thng k, cho nn y bng
chng cho thy khng c s publication bias.
Tuy nhin, nh thy trong thc t, nghim tan Egger ny cng ch l mt cch
th hin biu funnel m thi, ch cng khng c thay i g ln. C mt cch nh
gi publication bias, cho n nay, c xem l ng tin cy nht: l phng php phn
tch hi qui ng thng (linear regression) gia di v tng s mu (Ni). Ni cch khc,
chng ta tm a v b trong m hnh [7]:
di = a + b*Ni
Nu khng c publication bias th gi tr ca b s rt gn vi 0 hay khng c ngha
thng k. Nu tr s b khc vi 0 th l mt tn hiu ca publication bias. Trong v d
va nu vi d liu sau y,
Nghin cu

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

chng ta c phng trnh:

di = 16.0 - 0.0009*/Ni
v qu tht gi tr ca b qu thp (cng nh khng c ngha thng k), cho nn n y
chng ta c th kt lun rng khng c vn publication bias trong nghin cu va
cp n.
Ni tm li, qua phn tch tng hp ny, chng ta c bng chng ng tin cy
kt lun rng thi gian nm vin ca bnh nhn trong cc bnh vin a khoa di hn cc
bnh vin chuyn khoa khong 3 ngy ri, hoc trong 95% trng hp thi gian khc
bit khong t 2 ngy n 5 ngy. Kt qu ny cng cho thy khng c thin v xut bn
(publication bias) trong phn tch.
14.4.2 Phn tch tng hp bng R
R c hai package c vit v thit k cho phn tch tng hp. Package c s
dng kh thng dng l meta. Bn c c th ti min ph t trang web ca R (trong
phn packages): http://cran.R-project.org.

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)

Sau , chng ta s nhp s liu trong v d 1 vo R bin nh sau:

Nhp d liu cho tng ct trong Bng 1 v cho vo mt dataframe gi l los:

> n1 <- c(155,31,75,18,8,57,34,110,60)
> los1 <- c(55,27,64,66,14,19,52,21,30)
> sd1 <- c(47,7,17,20,8,7,45,16,27)
> n2 <- c(156,32,71,18,13,52,33,183,52)
> los2 <- c(75,29,119,137,18,18,41,31,23)
> sd2 <-c (64,4,29,48,11,4,34,27,20)

14

> los <- data.frame(n1,los1,sd1,n2,los2,sd2)

S dng hm

metacont (dng phn tch cc bin lin tc do

cont=continuous variable) v cho kt qu vo i tng res:

> res <- metacont(n1,los1,sd1,n2,los2,sd2,data=los)

> res
> res
WMD
95%-CI %W(fixed) %W(random)
1 -20 [-32.4744; -7.5256]
1.44
10.69
2 -2 [ -4.8271;
0.8271]
28.11
12.67
3 -55 [-62.7656; -47.2344]
3.73
11.89
4 -71 [-95.0223; -46.9777]
0.39
7.39
5 -4 [-12.1539;
4.1539]
3.38
11.80
6
1 [ -1.1176;
3.1176]
50.11
12.72
7 11 [ -8.0620; 30.0620]
0.62
8.76
8 -10 [-14.9237; -5.0763]
9.27
12.41
9
7 [ -1.7306; 15.7306]
2.95
11.67
Number of trials combined: 9
WMD
Fixed effects model
-3.4636
Random effects model -13.9817

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

meta cung cp cho chng ta hai kt qu: mt kt qu da vo m hnh fixed-effects v

mt da vo m hnh random-effects. Nh thy qua kt qu trn, mc khc bit gia
hai m hnh kh ln, nhng kt qu chung th ging nhau, tc kt qu ca c hai m hnh
u c ngha thng k.

Chng ta tt nhin cng c th s dng hm plot th hin kt qu trn bng biu

forest nh sau:
> plot(res, lwd=3)

15

-100

-80

-60

-40
-20
Weighted mean difference

20

14.5. Phn tch tng hp nh hng bt bin cho mt tiu

ch nh phn (Fixed-effects meta-analysis for a dichotomous
outcome).
Trong phn trn, ti va m t nhng bc chnh trong mt phn tch tng hp
nhng nghin cu m tiu ch l mt bin lin tc (continuous variable). i vi cc
bin lin tc, tr s trung bnh v lch chun l hai ch s thng k thng c s
dng tm lc. Nhng hai ch s ny khng th ng dng cho nhng tiu ch mang
tnh th loi hay th bc nh t vong, gy xng, v.v v nhng tiu ch ny ch c hai
gi tr: hoc l c, hoc l khng. Mt ngi hoc l cn sng hay cht, b gy xng
hay khng gy xng, mc bnh suy tim hay khng mc bnh suy tim, v.v i vi
nhng bin ny, chng ta cn mt phng php phn tch khc vi phng php dnh
cho cc bin lin tc.
14.5.1 M hnh phn tch

i vi nhng tiu ch nh phn (ch c hai gi tr), ch s thng k tng ng

vi tr s trung bnh l t l hay proportion, c th tnh phn trm); v ch s tng
ng vi lch chun l sai s chun (standard error). Chng hn nh nu mt
nghin cu theo di 25 bnh nhn trong mt thi gian, v trong thi gian c 5 bnh
nhn mc bnh, th t l (k hiu l p) n gin l: p = 5/25 = 0,20 (hay 20%). Theo l
thuyt xc sut, phng sai ca p (k hiu l var[p]) l: var[p] = p(1-p)/n = 0,2*(1 0,8)/25 = 0,0064.
Theo , sai s chun ca p (k hiu SE[p]) l:

16

SE [ p ] = var[ p ] = 0,0064 = 0,08. Chng ta cn c th c tnh khong tin cy 95%

ca t l nh sau: p 1,96 SE [ p ] = 0,2 1,96 0,08 = 0,04 n 0,36.

V cch tnh ca cc tiu ch nh phn kh c th, cho nn phng php phn

tch tng hp cc nghin cu vi bin nh phn cng khc. minh ha cch phn tch
tng hp dng ny, ti s ly mt v d (phng theo mt nghin cu c tht).
V d 2: Beta-blocker (s vit tt l BB) l mt loi thuc c chc nng iu tr
v phng chng cao huyt p. C gi thit cho rng BB cng c th phng chng bnh
suy tim, hay t ra l lm gim nguy c suy tim. th nghim gi thit ny, hng lot
nghin cu lm sng i chng ngu nhin c tin hnh trong thi gian 20 nm qua.
Mi nghin cu c 2 nhm bnh nhn: nhm c iu tr bng BB, v mt nhm khng
c iu tr (cn gi l placebo hay gi dc). Trong thi gian 2 nm theo di, cc nh
nghin cu xem xt tn s t vong cho tng nhm. Bng 2 sau y tm lc 13 nghin
cu trong qu kh:
Bng 2. Beta-blocker v bnh suy tim (congestive heart failure)
Nghin cu
(i)
1
2
3
4
5
6
7
8
9
10
11
12
13
Tng cng

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.

Nh chng ta thy, mt s nghin cu c s mu kh nh, li c nhng nghin cu vi s

mu gn 4000 ngi! Cu hi t ra l tng hp cc nghin cu ny, kt qu c nht
qun hay ph hp vi gi thit BB lm gim nguy c suy tim hay khng? tr li cu
hi ny, chng ta tin hnh nhng bc sau y:
Bc 1: c tnh mc nh hng cho tng nghin cu. Mi nghin cu c
hai t l: mt cho nhm BB v mt cho nhm placebo. Ti s gi hai t l ny l p1 v p2.
Ch s nh gi mc nh hng ca thuc BB l t s nguy c tng i (relative
risk RR), v RR c th c c tnh nh sau:

17

RR =

p1
p2

Chng hn nh, trong nghin cu 1, chng ta c: p1 =

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:

Nh vy t s nguy c cho nghin cu 1 l: RR =

Bng 2a. c tnh t l t vong v t s nguy c tng i

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

Bc 2: bin i RR thnh n v logarithm v tnh phng sai, sai s

chun. Mi c s thng k, nh c ln ni, u c mt lut phn phi, v lut phn
phi c th phn nh bng phn sai (hay sai s chun). Cch tnh phng sai ca RR kh
phc tp, cho nn chng ta s tnh bng mt phng php gin tip. Theo phng php
ny, chng ta s bin i RR thnh log[RR] (ch log y c ngha l loga t nhin,
tc l loge hay c khi cn vit tt l ln natural logarithm) , v sau s tnh phng sai
ca log[RR].

Nu N1 v N2 l ln lc tng s mu ca nhm 1 v nhm 2; v d1 v d2 l s t

vong ca nhm 1 v nhm 2 ca mt nghin cu, th phng sai ca log[RR] c th c
tnh bng cng thc sau y:
Var[logRR] =

1
1
1
1

d1 N1 d1 d 2 N 2 d 2

18

V sai s chun ca log[RR] l:

SE[logRR] =

1
1
1
1

d1 N 1 d1 d 2 N 2 d 2

Trong v d trn, vi nghin cu 1, chng ta c:

Log[RR] = loge(0.833) = -0.182
Vi phng sai:
var[log RR ] =

1
1
1
1

+
= 0.264
5 25 5 6 25 6

V sai s chun:

SE[log RR] = 0.264 = 0.514

Da vo lut phn phi chun, chng ta cng c th tnh ton khong tin cy 95% ca
RR cho tng nghin cu bng cch bin i ngc li theo n v RR. Chng hn nh
vi nghin cu 1, chng ta c khong tin cy 95% ca log[RR] l:
logRR 1.96*SE[logRR] = -0.182 1.96*0.514 = -1.19 n 0.82
hay bin i thnh n v nguyn thy ca RR l:
exp(-1.19) = 0.30 n exp(0.82) = 2.28
Tnh ton tng t cho cc nghin cu khc, chng ta c thm mt bng mi nh sau:
Bng 2b. c tnh t s nguy c tng i, phng sai, sai s chun v khong tin
cy 95% cho tng nghin cu

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

SE[logRR] Phn thp

95%CI
ca RR
0.514
0.30
1.142
0.09
0.282
0.61
1.189
0.05
0.842
0.12
0.162
0.58
0.854
0.14
0.377
0.14

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

Chng ta c th th hin RR v khong tin cy 95% bng biu forest nh sau:

Biu forest th hin gi tr ca RR v khong tin cy 95%. Cc c tnh khong

tin cy 95%CI ca RR vt qua ct mc 1 c xem l khng c ngha thng k.
Bc 3: c tnh trng s (weight) cho tng nghin cu v RR cho ton b
nghin cu. Biu trn cho thy mt s nghin cu c dao ng RR rt ln (chng
t cc nghin cu ny c s mu nh hay c s RR khng n nh), v ngc li, mt
s nghin cu ln c c s RR n nh hn. Trng s cho mi nghin cu (Wi ti s
cho vo k hiu i) o lng n nh ny l s o ca phng sai:

20

Wi =

1
var[log RRi ]

V s trung bnh trng s ca log[RR] (k hiu l logwRR) c th c tnh t tng ca

tch Wilog[RRi]:

W log[RR ]
i

log wRR =

Vi phng sai:
Var[logwRR] =

v sai s chun:
SE [log wRR ] =

Ngoi ra, khong tin cy 95% c th c tnh bng:

log wRR SE [log wRR ]

tnh trung bnh trng s logRR, chng ta cn mt ct Wilog[RRi]. Chng hn nh

vi nghin cu 1, chng ta c:
W1 =
v

1
= 3.79
0, 264

Wi log[RRi ] = 3.79 (-0.182) = -0.69

Tng t cho cc nghin cu khc:

Bng 2c. c tnh t trng s (Wi)

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:

=3.79 + 0.77 + + 5.75 = 284.24

W log[RR ] = -0.69 0.09 + -4.39 = -108.42

i

Do . trung bnh trng s ca log[RR] c th c tnh bng:

W log[RR ]
i

log wRR =

108, 42
= 0.38
284, 24

Vi phng sai:

Var [ log wRR ] =

1
= 0.0035
284.24

v sai s chun:
SE [ log wRR ] =

= 0.0035 = 0.06

Do . khong tin cy 95% ca logwRR c th c tnh bng:

log wRR SE [log wRR ] = -0.38 1.960.06 = 0.498 n -0.265

Nhng chng ta mun th hin bng n v gc (tc t s); do . cc c s trn phi

c bin chuyn v n v gc:
RR = exp(logwRR) = log(-0.38) = 0.68
V khong tin cy 95%:
Exp(-0.498) = 0.61 n Exp(-0.265) = 0.77.

22

n y chng ta c th ni rng t l t vong trong cc bnh nhn c iu tr

bng BB bng 0.68 (hay thp hn 32%) so vi cc bnh nhn gi dc (placebo). Ngoi
ra. v khong tin cy 95% khng bao gm 1. chng ta cng c th ni. mc khc bit
ny c ngha thng k.
Bc 4: c tnh ch s ng nht v bt ng nht. Nh ni trong phn
(1) lin quan n phn tch bin lin tc. sau khi c tnh t s nguy c trung bnh.
chng ta cn phi xem xt ch s I2.

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

Wi (log RRi log wRR ) = 3.79(-0.182 + 0.38)2 = 0.1502

2

v cho cc nghin cu khc:

Bng 2d. c tnh ch s heterogeneity (I2)

Nghin cu (i)
1
2
3
4
5
6
7
8
9
10
11
12
13
Tng s

Wi Wi (log RRi log wRR )2

3.79
0.1502
0.77
0.0533
12.61
2.5118
0.71
0.0687
1.41
0.0040
38.30
0.8635
1.37
0.0054
7.03
4.8731
4.13
0.0790
1.45
1.7074
110.78
0.0012
96.13
0.0253
5.75
0.8382
284.24
11.1811

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

Q = Wi ( log RRi log wRR ) = 11.1811

2

i =1

V.
I2 =

Q (k 1) 11.18 12
=
= 0.16
Q
11.18

23

V I2 < 0. nn chng ta c th cho I2 = 0. Ni cch khc. mc khc bit v RR gia

cc nghin cu khng c ngha thng k.
Bc 5: nh gi kh nng publication bias. Nh gii thch trong phn 1f.
cch nh gi kh nng publication bias c ngha nht l phn tch hi qui ng thng
log[RR] v tng s mu (N):
log[RRi] = a + bNi

Da vo bng thng k sau.

Nghin cu (i)
1
2
3
4
5
6
7
8
9
10
11
12
13

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

Chng ta c th c tnh a v b nh sau:

log[RRi] = -0.534 + 0.00003Ni
c tnh b = 0.00003 khng c ngha thng k (p = 0.782). Do . chng ta c th
pht biu rng mc thin lch v xut bn khng ng k trong phn tch tng hp
ny.

24

Biu funnel cng cho thy khng c vn publication bias

14.5.2 Phn tch bng R

Package meta c hm metabin c th s dng tin hnh phn tch tng hp

cho cc bin nh phn nh s liu trong v d 2 trn y. Khi u. chng ta np
package meta (nu cha lm) vo mi trng vn hnh. v sau thu nhp s liu vo
mt data frame:
library(meta)

# 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)

# Phn tch bng hm metabin v kt qu trong res

> res <- metabin(d1.n1.d2.n2.data=bb.sm=RR.meth=I)

> res
> res
RR
95%-CI %W(fixed) %W(random)
1 0.8333 [0.2918; 2.3799]
1.26
1.26
2 0.8889 [0.0930; 8.4951]
0.27
0.27
3 1.0670 [0.6116; 1.8617]
4.47
4.47
4 0.5000 [0.0484; 5.1677]
0.25
0.25
5 0.6476 [0.1240; 3.3814]
0.51
0.51
6 0.7935 [0.5731; 1.0986]
13.08
13.08

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

Number of trials combined: 13

RR
Fixed effects model 0.6821
Random effects model 0.6821

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

Kt qu t m hnh fixed-effects v random-effects mt ln na cho chng ta bng chng

kt lun rng beta-blocker c hiu nghim trong vic lm gim nguy c t vong.
# Biu forest
> plot(res. lwd=3)

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 :

xem xt nhng nghin cu no c tin hnh gii quyt vn ;

kt qu ca cc nghin cu nh th no;
h thng cc tiu ch lm sng ng quan tm;
r sot nhng khc bit v c tnh gia cc nghin cu;
cch thc tng hp kt qu; v
truyn t kt qu mt cch khoa hc.

Mc ch ca phn tch tng hp. xin nhc li mt ln na. l c tnh mt ch s

nh hng trung bnh sau khi xem xt tt c kt qu nghin cu hin hnh. Mt kt
qu chung nh th gip cho chng ta i n mt kt lun chnh xc v ng tin cy hn.
Hai v d trn y hi vng gip ch cho bn c hiu c c ch v ngha
ca mt phn tch tng hp. Hi vng bn c c th t mnh lm mt phn tch nh th
khi c d liu. Thc ra. tt c cc tnh ton trn c th thc hin bng mt phn mm
nh Microsoft Excel. Ngoi ra. mt s phn mm chuyn mn khc (nh SAS chng
hn) cng c th tin hnh nhng phn tch trn. Ti s gii thch phn ny trong phn k
tip). Cc php tnh tht n gin. Vn ca phn tch tng hp khng phi l tnh
ton. m l d liu ng sau tnh ton.
Phn tch tng hp cng khng phi l khng c nhng khim khuyt. Trong
nghin cu ngi ta c cu rc vo. rc ra. tc l nu cc d liu c s dng trong
phn tch khng c cht lng cao th kt qu ca phn tch tng hp cng chng c gi
tr khoa hc g. Do . vn quan trng nht trong phn tch tng hp l chn la d
liu v nghin cu phn tch. vn ny cn phi c cn nhc cc k cn thn
m bo tnh hp l v khoa hc ca kt qu.
Ti liu tham kho v ch thch

[1] Glass GV. Primary. secondary. and meta-analysis of research.

Researcher 1976; 5:3-8.

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

[4] Egger M. Davey Smith G. Schneider M. Minder C. Bias in meta-analysis detected by

a simple. graphical test. Br Med J 1997;315:62934.
[5] Tang JL. Liu JL. Misleading funnel plot for detection of bias in meta-analysis. J Clin
Epidemiol. 2000;53(5):477-84.
[6] Peters JL. Sutton AJ. Jones DR. Abrams KR. Rushton L. Comparison of two
methods to detect publication bias in meta-analysis. JAMA. 2006;295(6):676-80.
[7] Macaskill P. Walter SD. Irwig L. A comparison of methods to detect publication bias
in meta-analysis. Stat Med. 2001;20:641-654.

28

Tm tt phn tch tng hp

i vi cc bin s lin tc
Nhm 1 (s mu. trung bnh. lch
chun): n1i . x1i . s1i ; i = 1. 2. 3. . k
Nhm 2 (s mu. trung bnh. lch
chun): n2i . x2i . s2i
nh hng (effect size. ES):
d i = x2i x1i

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 =

x1i n1i x1i x2i n2i x2i

(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

x1i n1i x1i x2i n2i x2i

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

Khong tin cy 95%: d 1,96 s 2

Index of homogeneity:

Khong tin cy 95%: 1,96 s 2

Index of homogeneity:

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

c tnh phng sai gia cc nghin cu

(between-study variance):

Q (k 1)
2
= max 0,

k
2

Wi

k
i =1

Wi k
i =1
Wi

i =1

c tnh phng sai gia cc nghin cu

(between-study variance):

Q (k 1)
2 = max 0,

k
2

Wi

k
i =1

Wi k
i =1
Wi

i =1

30