14

Phn tch tng hp

Mt vn khoa hc cn n nhiu nghin cu. Mt nghin cu ring
l khng th gii quyt hay cung cp cu tr li dt khot cho mt vn khoa
hc. Nhu cu lp li nghin cu trong iu kin khc nhau rt quan trng trong
hot ng khoa hc. 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 nhng nm gn y, trong nghin cu khoa hc xut hin kh
nhiu nghin cu di danh mc meta-analysis, tm dch l phn tch tng
hp. Vy phn tch tng hp l g, mc ch, v cch tin hnh ra sao l nhng
cu hi m rt nhiu bn c mun bit. Chng ny ti s m t 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. 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 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. Tuy pht biu ny qu lc quan, nhng

19

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 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 hay khng.

14.2 Fixed-effects v Random-effects

Hai thut ng m bn c thng gp trong cc phn tch tng hp l
fixed-effects (tm dch l nh hng bt bin) v random-effects (nh hng
bin thin). hiu hai thut ng ny chng ta s xem xt 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 within-study variance) gy nn. Ci gi nh ng sau cch nhn thc ny
l: nu 100 nghin cu u c tin hnh ging 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.

20

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

2
Ch var[M] = 0 v M l mt hng s bt bin, se l phng sai ca ei .
2
Mc ch ca phn tch tng hp l c tnh M v se .

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 bnh ca qun th

21

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 :

Do :

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

2
Nh ta thy qua cng thc ny, s phn nh dao ng gia cc nghin cu
2
(between-study variation), cn se phn nh dao ng trong mi nghin cu
(within-study variation). Mc ch ca phn tch tng hp nh hng bin thin
2
2
l c tnh M, se v s .

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
2
hp bt bin xem s = 0, th phn tch tng hp bin thin t yu cu phi
2
2
c tnh s . Tt nhin, nu s = 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.

22

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 thu thp 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.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 . Phn di y 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. Chng ta s ln lc m t hai phng php
chnh cho hai loi bin s lin tc v nh phn.

23

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 chuyn 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
Bnh vin chuyn khoa
Bnh vin a khoa
cu (i)
N1i
LOS1i
SD1i
N2i
LOS2i
SD2i
1
155
55
47
156
75
64
2
31
27
7
32
29
4
3
75
64
17
71
119
29
4
18
66
20
18
137
48
5
8
14
8
13
18
11
6
57
19
7
52
18
4
7
34
52
45
33
41
34
8
110
21
16
183
31
27
9
60
30
27
52
23
20
Tng cng
548
610
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.

24

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 chng ta s
t k hiu l di. Ch s nh hng ny ch n gin l:

di = LOS1i LOS2i
2
Phng sai ca di (ti s k hiu l si ) 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:

2
i

(
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:
2
1

( 155 1) ( 47 )
=

+ ( 156 1) ( 64 ) 1
1
+

= 40.59
155 + 156 2
155 156
2

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:
di - 1.96*si = 20 1.96*6.37 = 7.71 ngy
n
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%

25

Nghin cu (i)

di

1
2
3
4
5
6
7
8
9

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
7.51
-0.80
47.34
46.98
-4.81
-3.17
-30.14
4.45
-15.92

di+1.96*si
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
2
(Wi) thc ra ch l s o ca phng sai si ,

Wi = 1 / si2

26

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

di

1
2
3
4
5
6
7
8
9
Tng s

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

27

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

2
trong trng hp d, phng sai (k hiu l sd ) ch n gin l s o ca tng
trng s Wi:

sd2 =

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

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

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

28

0.4928 + 0.9771 + ... 0.3383 5.7140

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

2
V phng sai ca d l: sd =

1
= 0.61 .
1.6345

Ni cch khc, sai s chun (standard error) ca d l:

sd = 0.61 = 0.782 .
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
2
2
k-1 (tc l k 1 ). Ni cch khc, nu Q ln hn k 1 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), 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.

29

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
3
4
5
6
7
8
9
Tng s

20
2
55
71
4
-1
-11
10
-7

40.6
2.0
15.3
150.2
20.2
1.2
95.4
8.0
20.7

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

Wi ( d i d )

6.7129
1.0903
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

30

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

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

di

1
2
3
4
5
6
7
8
9

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

31

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.
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.
Kim nh 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 kim nh Egger (cn gi l
Egger's test). Vi phng php ny, chng ta m hnh rng SND = a + b x
precision, trong SND c c tnh bng cch ly d chia cho sai s chun
ca d, tc l: SNDi =

di
, a v b l hai thng s phi c tnh t m hnh hi
sdi

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.

32

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, kim nh 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
1
2
3
4
5
6
7
8
9

di
20
2
55
71
4
-1
-11
10
-7

Ni
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

33

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)
> 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

34

Number of trials combined: 9

WMD
Fixed effects model -3.464
Random effects model -13.98

95%-CI
[ -4.96; -1.96]
[-24.03; -3.93]

z
-4.53
-2.73

p.value
<0.0001
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 fixedeffects 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.
Ngoi ra, chng ta cng c th s dng hm plot th hin kt qu trn bng
biu forest nh sau:
> plot(res, lwd=3)

-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 metaanalysis for a dichotomous outcome).

35

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:
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, chng ta s ly mt v d (phng theo
mt nghin cu c tht).
V d 2: Beta-blocker (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:

36

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 (gi dc).
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:

RR =

p1
p2

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

p2 =

8
= 0,24 .
25

RR =

5
= 0,20 v
25

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

0,20
= 0,833 . Tnh ton tng t cho cc nghin cu cn li, chng ta
0,24

s c mt bng nh sau:
Bng 2a. c tnh t l t vong v t s nguy c tng i

37

Nghin cu (i)

T l t vong
nhm BB (p1)

1
2
3
4
5
6
7
8
9
10
11
12
13

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 N 1 d1 d 2 N 2 d 2

V sai s chun ca log[RR] l:

SE[logRR] =

1
1
1
1

d1 N1 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 ] =

38

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)

T s
nguy
c
(RR)

Log[RR]

Var[logRR]

SE[logRR]

Phn
thp
95%CI
ca RR

1
2
3
4
5
6
7
8
9
10
11
12
13

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

-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

0.264
1.304
0.079
1.415
0.709
0.026
0.729
0.142
0.242
0.688
0.009
0.010
0.174

0.514
1.142
0.282
1.189
0.842
0.162
0.854
0.377
0.492
0.829
0.095
0.102
0.417

0.30
0.09
0.61
0.05
0.12
0.58
0.14
0.14
0.23
0.05
0.56
0.55
0.21

Phn
cao
95%
CI ca
RR
2.28
8.33
1.85
5.15
3.37
1.09
3.87
0.62
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:

39

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 cho vo k hiu i) o lng n nh ny l s
o ca phng sai:
1
Wi =
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:

40

1
Var[logwRR] =

v sai s chun:

SE [ log wRR ] =

i1

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

Tnh ton tng t cho cc nghin cu khc, chng ta s c mt bng s liu

mi nh sau:
Bng 2c. c tnh t trng s (Wi)
Nghin cu (i)
1
2
3
4
5
6
7
8
9
10
11
12
13
Tng s
Chng ta c:

Log[RR]
-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

Var[logRR]
0.264
1.304
0.079
1.415
0.709
0.026
0.729
0.142
0.242
0.688
0.009
0.010
0.174

Wi
3.79
0.77
12.61
0.71
1.41
38.30
1.37
7.03
4.13
1.45
110.78
96.13
5.75
284.24

Wilog[RRi]
-0.69
-0.09
0.82
-0.49
-0.61
-8.86
-0.44
-8.54
-2.15
-2.13
-42.63
-38.23
-4.39
-108.42

41

=3.79 + 0.77 + + 5.75 = 284.24

log[ RRi ] = -0.69 0.09 + -4.39 = -108.42

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.
n y chng ta c th ni rng t l t vong trong cc bnh nhn
c iu tr bng BB l 0.68 (hay thp hn 32%) so vi cc bnh nhn
placebo. Ngoi ra. v khong tin cy 95% khng bao gm 1, chng ta cng c
th pht biu rng 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,

42

chng ta cn tnh Wi ( log RRi log wRR )

nh vi nghin cu 1, chng ta c:

cho mi nghin cu. Chng hn

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

2

v tnh ton tng t cho cc nghin cu khc, chng ta s c mt bn s liu

mi nh sau:
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

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

Wi

Wi ( log RRi log wRR )

3.79
0.77
12.61
0.71
1.41
38.30
1.37
7.03
4.13
1.45
110.78
96.13
5.75
284.24

0.1502
0.0533
2.5118
0.0687
0.0040
0.8635
0.0054
4.8731
0.0790
1.7074
0.0012
0.0253
0.8382
11.1811

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

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):

43

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.

Biu funnel cng cho thy khng c vn publication bias

14.5.2 Phn tch bng R

44

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
7 0.7273 [0.1346; 3.9282]
0.49
0.49
8 0.2971 [0.1410; 0.6258]
2.49
2.49
9 0.5947 [0.2262; 1.5632]
1.48
1.48
10 0.2310 [0.0454; 1.1744]
0.52
0.52
11 0.6806 [0.5635; 0.8221]
38.81
38.81
12 0.6719 [0.5496; 0.8214]
34.31
34.31
13 0.4662 [0.2056; 1.0570]
2.07
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

45

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

***
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

46

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. Cc php tnh trong phn tch tng hp 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. Educational
Researcher 1976; 5:3-8.
[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
[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 metaanalysis. 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.

47

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): n2 i . x2 i . s2 i
nh hng (effect size. ES):
d i = x2i x1i

Phng sai ca d i :

(
n1i 1) s12i + ( n2i 1) s22i
=

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 i :

1
1
1
1 s2i = 1 1
+

+
x1i n1i x1i x2i n2i x2i
n

n1i + n2i 2
1i n2i
Sai s (standard error) ca d i :
Sai s ca i :

2
di

sdi = sdi2

1
1
1
1

x1i n1i x1i x2 i n2i x2 i

s =

1
sdi2
c s nh hng chung:

1
s2i
c s nh hng chung:

Trng s: Wi =
k

i =1

i =1

Trng s: Wi =
k

i =1

i =1

d= Wi d i / Wi

= Wii / Wi

Phng sai ca d:

Phng sai ca :

s 2 = 1 / Wi

s 2 = 1 / Wi

i =1

i =1

Khong tin cy 95%:

d 1,96 s

Index of homogeneity:
k

Q = Wi ( d i d )

i =1

Index of heterogeneity:

48

Khong

tin

1,96 s

cy

Index of homogeneity:
k

Q = Wi (i )

i =1

Index of heterogeneity:

95%:

I2 =

Q ( k 1)
Q

I2 =

Q ( k 1)
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.

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.

c tnh phng sai gia cc nghin

cu (between-study variance):

c tnh phng sai gia cc

nghin cu (between-study
variance):

2
=max 0,

Q ( k 1)

k
2
W

i
k

Wi i =k1

i =1
Wi

i =1

2 =max 0,

Q ( k 1)

k
Wi 2

Wi i =k1

i =1
Wi

i =1

49