1

Phng php c tnh c mu

cho mt nghin cu y hc

Nguyn Vn Tun

Mt cng trnh nghin cu thng da vo mt mu (sample). Mt trong nhng
cu hi quan trng nht trc khi tin hnh nghin cu l cn bao nhiu mu hay bao
nhiu i tng cho nghin cu. i tng y l n v cn bn ca mt nghin
cu, l s bnh nhn hay s tnh nguyn vin. c tnh s lng i tng cn thit cho
mt cng trnh nghin cu ng vai tr cc k quan trng, v n c th l yu t quyt
nh s thnh cng hay tht bi ca nghin cu. Nu s lng i tng khng th kt
lun rt ra t cng trnh nghin cu khng c chnh xc cao, thm ch khng th kt
lun g c. Ngc li, nu s lng i tng qu nhiu hn s cn thit th ti
nguyn, tin bc v thi gian s b hao ph. Do , vn then cht trc khi nghin cu
l phi c tnh cho c mt s i tng va cho mc tiu ca nghin cu. S
lng i tng va ty thuc vo loi hnh nghin cu v hai thng s chnh:

Phng php thit k nghin cu v tiu ch lm sng (outcome measure).
H s nh hng (effect size);
Sai lm m nh nghin cu chp nhn, c th l sai lm loi I v II (power);

Khng bit [hay cha quyt nh] c thit k nghin cu v khng c s liu v
hai thng s trn th khng th no c tnh c mu. Kinh nghim ca ngi vit cho
thy rt nhiu ngi khi tin hnh nghin cu thng khng c nim g v cc s liu
ny, cho nn khi n tham vn cc chuyn gia v thng k hc, h ch nhn cu tr li:
khng th tnh c! Trong bi ny ti s bn qua hai thng s trn v trnh by mt
s v d nghin cu lm sng c th v c tnh c mu.

1. Thit k nghin cu v tiu ch lm sng

1.1 Thit k nghin cu

Thng tin th nht trong qui trnh c tnh c mu l th loi nghin cu, bi v
yu t ny c nh hng n phng php phn tch thng k v v th phng php c
tnh c mu. C th phn bit cc th loi nghin cu ny da vo hai tiu ch: thi gian
v c tnh. V thi gian, cc nghin cu thu thp d liu ti mt thi im hin ti
(present) c gi l cross-sectional study (nghin cu tiu biu mt thi im); cc
nghin cu c nh hng theo di tnh trng sc khe ca i tng trong mt thi gian,
tc thu thp d liu tng i tng nhiu ln (hin ti v tng lai) c gi l
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prospective (hay longitudinal) study (nghin cu theo thi gian); v cc nghin cu c
tin hnh hin ti nhng c nh hng tm hiu qu kh (past) c gi l retrospective
study.

Nghin cu ti mt thi im hay cross-sectional study (c dch theo ngha en
l nghin cu ct ngang). y l mt thit k m cc nh nghin cu chn mt qun
th mt cch ngu nhin nhng tiu biu cho mt cng ng, ti mt thi im no .
Ni cch khc, nh nghin cu thu thp d liu ch mt ln duy nht ca cc i tng
ngay ti thi im (hin ti). Mc ch chnh ca cc nghin cu ny l tm hiu t l
hin hnh (prevalence) ca mt bnh no , hay tm hiu mi tng quan gia mt yu
t nguy c v mt bnh.

Nghin cu i chng hay case-control study. Trong cc nghin cu ny, mc
ch chnh l tm hiu mi lin h gia mt (hay nhiu) yu t nguy c (risk factors) v
mt bnh rt c th. tin hnh nghin cu ny, nh nghin cu bt u bng mt
nhm bnh nhn v mt nhm i tng khng bnh (i chng), v i ngc thi
gian tm hiu nhng yu t nguy c m c hai nhm phi nhim trong qu kh.

Nghin cu xui thi gian (longitudinal studies hay prospective study). Ngc
li vi nghin cu i chng (trng hp nh nghin cu bit ai mc bnh v ai khng
mc bnh), vi cc nghin cu theo thi gian nh nghin cu bt u bng mt nhm
khng mc bnh, v theo di mt thi gian sau quan st ai mc bnh hay khng mc
bnh trong thi gian . Ngc li vi nghin cu i chng (trng hp nh nghin
cu i ngc v qu kh tm hiu ai b phi nhim yu t nguy c), vi cc nghin
cu theo thi gian, nh nghin cu bit ngay t lc ban u ai b phi nhim hay khng
phi nhim yu t nguy c. Mc ch ca cc nghin cu xui thi gian thng l c
tnh t l pht sinh (incidence) bnh trong mt thi gian (iu ny khc vi mc ch ca
nghin cu ti mt thi im l c tnh t l hin hnh tc prevalence ca bnh).
Ngoi ra, cc nghin cu theo thi gian cn cho php nh nghin cu tm hiu mi lin
h gia mt hay nhiu yu t nguy c v nguy c pht sinh bnh tt. Khc vi nghin
cu cross-section ch ghi nhn s kin ti mt thi im, cc nghin cu longitudinal
phi theo di i tng trong mt thi gian c th l nhiu nm thng.

1.2 Tiu ch lm sng

Sau khi xc nh th loi nghin cu, nh nghin cu cn phi quyt nh chn
mt tiu ch lm sng chnh (primary outcome measure) cn c vo m c tnh c
mu. Quyt nh chn tiu ch lm sng l mt quyt nh va mang tnh lm sng, va
mang tnh khoa hc. Bi v mc tiu ti hu ca nghin cu y khoa l em li li ch cho
bnh nhn hay cng ng, cho nn tiu ch c chn phi c ngha thc t i vi
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bnh nhn. Chng hn nh trong vic thm nh hiu qu ca cc phng php truy tm
ung th, th t l pht hin ung th v iu tr khng phi l tiu ch c ngha thc t,
nhng t l t vong v thi gian sng st sau khi truy tm ung th mi l tiu ch c
ngha lm sng v thc t. Mc khc, tiu ch phi p ng cc tiu chun khoa hc v
tin cy v chnh xc. Nu mt nghin cu c mc tiu tm hiu hiu qu ca mt
loi thuc phng chng bnh x va ng mch, th cholesterol trong mu khng th
c xem l tiu ch c ngha lm sng, d n p ng yu cu khoa hc tnh. Do ,
vic chn mt tiu ch lm sng cho nghin cu cn phi cn nhc rt cn thn.

Quyt nh chn tiu ch lm sng l mt quyt nh quan trng, bi v n c nh
hng n c mu rt ln. Chng hn nh trong cc nghin cu long xng, cc nh
nghin cu c th so snh mt xng hay t l gy xng gia hai nhm can thip
bit hiu qu ca thuc. Nu chn mt xng lm tiu ch lm sng th s lng c
mu c th s l con s vi trm bnh nhn, nhng nu chn t l gy xng con s c
mu c th ln n vi chc ngn i tng.


2. Khi nim v h s nh hng (effect size)

H s nh hng, ni mt cch n gin, l mt ch s v nh hng ca mt
thut can thip. V phn nh mc khc bit, h s nh hng cho php chng ta trnh
khi cch din dch gii hn bi ngn ng nh phn (nh c hay khng c nh
hng?), v tp trung vo mt cch din dch mang tnh khoa hc hn (nh mc
nh hng cao hay thp c no?) Ba trng hp n gin sau y s minh ha cho khi
nim v h s nh hng:

Trng hp 1: Trong mt nghin cu gm 50 bnh nhn cao huyt p c iu
tr bng mt thuc trong nhm beta-blocker. Trc khi iu tr, huyt p tm thu (SBP)
trung bnh cho c nhm l 140 mmHg v lch chun l 22 mmHg. Sau khi iu tr,
huyt p tm thu gim xung cn 125 mmHg.

Trng hp 2: Mt nghin cu khc thm nh hiu qu ca mt thuc chng
long xng trong nhm bisphosphonate. Nghin cu c tin hnh trn 50 bnh nhn.
Trc khi iu tr, mt xng c xng i (femoral neck bone mineral density, vit
tt l BMD) trung bnh l 0.68 g/cm
2
vi lch chun 0.12 g/cm
2
. Sau 6 thng iu tr,
BMD trung bnh cho c nhm tng ln 0.72 g/cm
2
vi

lch chun 0.13 g/cm
2
.

Trng hp 3: Mt nghin cu bnh chng (case-control study) nhm thm
nh nh hng ca thi quen ht thuc l n glucose trong mu. Nhm ht thuc l
gm 30 ngi c glucose trung bnh l 130 mg/dL vi lch chun 35 mg/dL.
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Nhm khng ht thuc l gm 70 ngi c glucose trung bnh l 110 mg/dL vi
lch chun 50 mg/dL.

Trong trng hp 1, chng ta c th c tnh mc nh hng bng cch ly
huyt p sau khi iu tr tr cho huyt p trc khi iu tr: d
1
= 125 140 = -15 mmHg.
Tng t, nh hng ca thuc bisphosphonate cho trng hp 2 l d
2
= 0.72 0.68 =
0.04 g/cm
2
. V trng hp 3, nh hng ca ht thuc l c th c tnh bng d3 =
130 110 = 20 mg/dL.

Kh khn trong cch c tnh nh hng trn y l khng th so snh trc
tip c nh hng, bi v n v o lng khc nhau. V, quan trng hn na,
dao ng (phn nh bng lch chun) gia 3 trng hp cng rt khc nhau. Phng
php so snh trc tip nh hng l tng l hon chuyn sao cho c ba trng hp c
cng mt n v o lng. t c mc ch ny, cch n gin nht l ly nh
hng chia cho lch chun. T s ny c tn ting Anh l effect size (c khi cn gi l
standardized difference) m ti tm dch l h s nh hng. Cng thc chung cho c
tnh h s nh hng (s vit tt bng ES) l:

1 0
0
x x
ES
s

= [1]
Trong :

1
x l s trung bnh ca nhm can thip;

0
x l s trung bnh ca nhm i chng; v

0
s l lch chun ca nhm i chng.

H s nh hng ca 3 trng hp trn l:

Trng hp 1: ES
1
= -15 / 22 = 0.68
Trng hp 2: ES
2
= 0.04 / 0.12= 0.33
Trng hp 3: ES
3
= 20 / 50 = 0.40

Nn nh rng lch chun c cng n v o lng vi nh hng trung bnh, cho
nn h s nh hng khng c n v. Ni cch khc, n v o lng nh hng by
gi l lch chun. Chng hn nh trong trng hp 1, thuc beta-blocker c tc dng
gim huyt p tm thu khong 0.68 lch chun, cn trong trng hp 2, thuc
bisphosphonate tng mt xng ch 0.33 lch chun. V c cng n v so snh, c
th ni [n gin] rng h s nh hng ca thuc beta-blocker cao hn thuc
bisphosphonate.

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Theo mt qui c [khng c c s khoa hc my], mt h s nh hng bng 0.2
c xem l thp, 0.5 l trung bnh, v >0.8 l cao [1]. Mt h s nh hng 0.2
tng ng vi khc bit v chiu cao ca mt em b 15 tui v mt em b 16 tui.
Mt h s nh hng 0.5 tng ng vi khc bit v chiu cao ca mt em b 14
tui v mt em b 18 tui. Mt h s nh hng 0.8 tng ng vi khc bit v ch
s thng minh (IQ) ca mt sinh vin nm th nht v mt tin s.


3. Sai lm loi I, II v khi nim v power

3.1 Sai lm loi I v II

Thng k hc l mt phng php khoa hc c mc ch pht hin, hay i tm
nhng ci c th gp chung li bng cm t cha c bit (unknown). Ci cha c
bit y l nhng hin tng chng ta khng quan st c, hay quan st c nhng
khng y . Ci cha bit c th l mt n s (nh chiu cao trung bnh ngi Vit
Nam, hay trng lng mt phn t), hiu qu ca mt thut iu tr, t l lu hnh
(prevalence), t l pht sinh (incidence) ca bnh, v.v Chng ta c th o chiu cao,
hay tin hnh xt nghim bit hiu qu ca thuc, nhng cc nghin cu nh th ch
c tin hnh trn mt nhm i tng, ch khng phi ton b qun th ca dn s.
Vn l s dng kt qu ca mt nhm i tng suy lun cho mt qun th ln
hn. Mc ch ca c tnh c mu l tm s lng i tng sao cho suy lun t
chnh xc cao nht v y nht.

mc n gin nht, nhng ci cha bit ny c th xut hin di hai hnh
thc: hoc l c, hoc l khng. Chng hn nh mt thut iu tr c hay khng c hiu
qu chng gy xng. Bi v khng ai bit hin tng mt cch y , chng ta phi
t ra gi thit. Gi thit n gin nht l gi thit o (hin tng khng tn ti, k hiu
Ho) v gi thit chnh (hin tng tn ti, k hiu Ha).

Chng ta s dng cc phng php kim nh thng k (statistical test) nh kim
nh t, F, z,
2
, v.v nh gi kh nng ca gi thit. Kt qu ca mt kim nh
thng k c th n gin chia thnh hai gi tr: hoc l c ngha thng k (statistical
significance), hoc l khng c ngha thng k (non-significance). C ngha thng k
y thng da vo tr s P: thng thng, nu P < 0.05, chng ta pht biu kt qu c
ngha thng k; nu P > 0.05 chng ta ni kt qu khng c ngha thng k. Cng c
th xem c ngha thng k hay khng c ngha thng k nh l c tn hiu hay khng
c tn hiu. Hy tm t k hiu T+ l kt qu c ngha thng k, v T- l kt qu kim
nh khng c ngha thng k.

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Hy xem xt mt v d c th: bit thuc risedronate c hiu qu hay khng
trong vic iu tr long xng, chng ta tin hnh mt nghin cu gm 2 nhm bnh
nhn (mt nhm c iu tr bng risedronate v mt nhm ch s dng gi dc
placebo). Chng ta theo di v thu thp s liu gy xng, c tnh t l gy xng cho
tng nhm, v so snh hai t l bng mt kim nh thng k. Kt qu kim nh thng
k hoc l c ngha thng k (P<0.05) hay khng c ngha thng k (P>0.05). Xin
nhc li rng chng ta khng bit risedronate tht s c hiu nghim chng gy xng
hay khng; chng ta ch c th t gi thit. Do , khi xem xt mt gi thit v kt qu
kim nh thng k, chng ta c bn tnh hung:

(a) Gi thuyt Ha ng (thuc risedronate c hiu nghim) v kt qu kim nh thng
k P<0.05.

(b) Gi thuyt Ha ng, nhng kt qu kim nh thng k khng c ngha thng k;

(c) Gi thuyt Ha sai (thuc risedronate khng c hiu nghim) nhng kt qu kim
nh thng k c ngha thng k;

(d) Gi thuyt Ha sai v kt qu kim nh thng k khng c ngha thng k.

y, trng hp (a) v (d) khng c vn , v kt qu kim nh thng k nht qun
vi thc t ca hin tng. Nhng trong trng hp (b) v (c), chng ta phm sai lm, v
kt qu kim nh thng k khng ph hp vi gi thit. Trong ngn ng thng k hc,
chng ta c vi thut ng:

xc sut ca tnh hung (b) xy ra c gi l sai lm loi II (type II error), v
thng k hiu bng .

xc sut ca tnh hung (a) c gi l Power. Ni cch khc, power chnh l xc
sut m kt qu kim nh thng cho ra kt qu p<0.05 vi iu kin gi thit Ha
l tht. Ni cch khc: power = 1- ;

xc sut ca tnh hung (c) c gi l sai lm loi I (type I error, hay
significance level), v thng k hiu bng . Ni cch khc, chnh l xc sut
m kt qu kim nh thng cho ra kt qu p<0.05 vi iu kin gi thit Ha sai;

xc sut tnh hung (d) khng phi l vn cn quan tm, nn khng c thut
ng, d c th gi l kt qu m tnh tht (hay true negative).

C th tm lc 4 tnh hung trong mt Bng 1 sau y:
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Bng 1. Cc tnh hung trong vic th nghim mt gi thit khoa hc

Gi thuyt Ha
Kt qu kim nh thng
k
ng
(thuc c hiu nghim)

Sai
(thuc khng c hiu nghim)

C ngha thng k
(p<0,05)

Dng tnh tht (power),
1-= P(S | Ha)


Sai lm loi I (type I error)
= P(S | Ho)

Khng c ngha thng k
(p>0,05)

Sai lm loi II (type II error)
= P(NS | Ha)

m tnh tht (true negative)
1- = P(NS | Ho)

Ch thch: k hiu S trong bng ny c ngha l significant (tc p<0.05); NS = non-
significant (tc p>0.05). Do , c th m t 4 tnh hung trn bng ngn ng xc sut c iu
kin nh sau: Power = 1 = P(S | Ha); = P(NS | Ha); v = P(S | Ho). Xin nhc li rng k
hiu ton hc P(A | B) c ngha l mt xc sut c iu kin, c th hn k hiu P(S | Ha) c
ngha l xc sut S xy ra nu (hay vi iu kin) Ha l ng.

3.2 Kim nh gi thit thng k v chn on y khoa

C l nhng l gii trn y, i vi mt s bn c, vn cn kh tru tng. Mt
cch minh ha cc khi nim power v tr s P l qua chn on y khoa. Tht vy, c
th v nghin cu khoa hc v suy lun khoa hc nh l mt qui trnh chn on bnh.
Trong chn on, thot u chng ta khng bit bnh nhn mc bnh hay khng, v phi
thu thp thng tin (nh tm hiu tin s bnh, cch sng, thi quen, v.v) v lm xt
nghim (nh quang tuyn X, nh siu m, phn tch mu, nc tiu, v.v) i n kt
lun.

C hai gi thit: bnh nhn khng c bnh (k hiu Ho) v bnh nhn mc bnh
(Ha). mc n gin nht, kt qu xt nghim c th l dng tnh (+ve) hay m
tnh (-ve). Trong chn on cng c 4 tnh hung v ti s bn trong phn di y,
nhng vn r rng hn, chng ta hy xem qua mt v d c th nh sau:

Trong chn on ung th, bit chc chn c ung th hay khng, phng php
chun l dng sinh thit (tc gii phu xem xt m di ng knh hin vi xc nh
xem c ung th hay khng c ung th. Nhng sinh thit l mt phu thut c tnh cch
xm phm vo c th bnh nhn, nn khng th p dng phu thut ny mt cch i tr
cho mi ngi. Thay vo , y khoa pht trin nhng phng php xt nghim khng
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mang tnh xm phm th nghim ung th. Cc phng php ny bao gm quang
tuyn X hay th mu. Kt qu ca mt xt nghim bng quang tuyn X hay th mu c
th tm tt bng hai gi tr: hoc l dng tnh (+ve), hoc l m tnh (-ve).

Nhng khng c mt phng php th nghim gin tip no, d tinh vi n u
i na, l hon ho v chnh xc tuyt i. Mt s ngi c kt qu dng tnh, nhng
thc s khng c ung th. V mt s ngi c kt qu m tnh, nhng trong thc t li
c ung th. n y th chng ta c bn kh nng:

Bnh nhn c ung th, v kt qu th nghim l dng tnh. y l trng hp
dng tnh tht (danh t chuyn mn l nhy, ting Anh gi l sensitivity);

bnh nhn khng c ung th, nhng kt qu th nghim l dng tnh. y l
trng hp dng tnh gi (false positive);

bnh nhn khng c ung th, nhng kt qu th nghim l m tnh. y l trng
hp ca m tnh tht (specificity); v,

bnh nhn c ung th, v kt qu th nghim l m tnh. y l trng hp m
tnh gi hay c hiu (false negative).

C th tm lc 4 tnh hung trong Bng 2 sau y:

Bng 2. Cc tnh hung trong vic chn on y khoa: kt qu xt nghim v bnh
trng

Bnh trng
Kt qu xt nghim C bnh

Khng c bnh

+ve (dng tnh)

nhy hay dng tnh tht
(sensitivity),


Dng tnh gi (false positive)


-ve (m tnh)

m tnh gi (false negative),


c hiu hay m tnh tht
(Specificity),



n y, chng ta c th nhn ra mi tng quan song song gia chn on y
khoa v kim nh mt gi thit khoa hc. Trong chn on y khoa c ch s dng tnh
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tht, tng ng vi khi nim power trong nghin cu khoa hc. Trong chn on y
khoa c xc sut dng tnh gi, v xc sut ny chnh l tr s p trong suy lun khoa hc.
Bng sau y s cho thy mi tng quan :

Bng 3. Tng quan gia chn on y khoa v suy lun trong khoa hc

Chn on y khoa Kim nh gi thit khoa hc
Chn on bnh Th nghim mt gi thit khoa hc
Bnh trng (c hay khng) Gi thit khoa hc (Ha hay Ho)
Phng php xt nghim Kim nh thng k
Kt qu xt nghim +ve Tr s p < 0.05 hay c ngha thng k
Kt qu xt nghim ve Tr s p > 0.05 hay khng c ngha thng
k
Dng tnh tht (sensitivity) Power; 1-; P(s | Ha)
Dng tnh gi (false positive) Sai lm loi I; tr s p; ; P(S | Ho)
m tnh gi (false negative) Sai lm loi II; ; = P(NS | Ha)
m tnh tht (c hiu, hay specificity) m tnh tht; 1- = P(NS | Ho)

Cng nh cc phng php xt nghim y khoa khng bao gi hon ho, cc
phng php kim nh thng k cng c sai st. V do , kt qu nghin cu lc no
cng c bt nh (nh s bt nh trong mt chn on y khoa vy). Vn l chng
ta phi thit k nghin cu sao cho sai st loi I v II thp nht.


4. Phng php c tnh c mu

Nh cp trong phn u ca bi vit, c tnh s i tng cn thit cho
mt cng trnh nghin cu, ngoi th loi nghin cu, chng ta cn phi c 3 s liu: xc
sut sai st loi I v power, v h s nh hng. S lng c mu l hm s ca ba thng
s ny. Gi n l s lng c mu cn thit, l sai st loi I, l sai st loi II (tc 1-
l power), h s nh hng l ES, th cng thc chung c tnh c mu l:

( )
( )
2
2
2 /
ES
z z
n
b
+
=

Trong ,
2 /
z v

z l nhng hng s (tht ra l s lch chun) t phn phi chun

(standardized normal distribution) cho xc sut sai st v . Bi v, trong cng thc
trn ES l mu s, cho nn nu ES thp th s lng c mu s tng; ngc li, nu ES
cao th s lng c mu s gim.

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V nh hng nh th, h s nh hng phi c gi nh trc khi tnh ton.
y l thng s khng phi lc no cng c sn, cho nn nh nghin cu cn phi xem
xt cc nghin cu trc hay nh hng c ngha lm sng tnh ton c mu.

V xc sut sai st, thng thng mt nghin cu chp nhn sai st loi I khong
1% hay 5% (tc = 0.01 hay 0.05), v xc sut sai st loi II khong = 0.1 n = 0.2
(tc power phi t 0.8 n 0.9). Mi trng hp gn lin vi mt hng s
2 /
z v

z
nh va cp. Hai hng s ny c th tm gn bng cng thc ( )
2
2 / b
z z C + =

. C
c xc nh bi lut phn phi chun nh trnh by trong Bng 3 di y. Chng hn
nh nu mun = 0.05 v power = 0.80, th hng s C l 7.85.

Bng 3: Hng s C lin quan n sai st loi I v II

= = 0.20
(Power = 0.80)
= 0.10
(Power = 0.90)
= 0.05
(Power = 0.95)
0.10 6.15 8.53 10.79
0.05 7.85 10.51 13.00
0.01 13.33 16.74 19.84


4.1 Cc nghin cu vi tiu ch l bin lin tc (continuous variable)

4.1.1 Trong trng hp nghin cu ch c mt nhm i tng, v mc tiu l
c tnh mt ch s trung bnh (k hiu ) vi mt sai s nh trc l . Vi nghin cu
nh th, h s nh hng c th c tnh bng ES = /. V s i tng (n) cn thit
cho nghin cu c th tnh ton theo cng thc sau y:

( )
2
C
n
ES
= [2]

Trong , C l hng s t Bng 3.

4.1.2 Trong trng hp nghin cu trc-sau (before-after studies). Nhiu
nghin cu can thip trn mt nhm bnh nhn, m theo tiu ch lm sng mi bnh
nhn c o lng hai ln: trc khi can thip v sau khi can thip. Trong thut ng
dch t hc, ngi ta gi l nghin cu trc-sau (before-after study). Chng hn nh
nh gi hiu qu ca mt loi thuc iu tr cao huyt p, cc nh nghin cu c th
chn mt nhm bnh nhn thch hp, sau o lng huyt p trc khi iu tr v sau
11
khi iu tr. H s nh hng c th tnh t khc bit gia hai thi im, nhng y
cn mt thng s lin quan khc: l h s tng quan gia hai ln o lng.

Gi o lng trc khi iu tr ca bnh nhn i l
i
X v sau khi iu tr l
i
Y .
nh hng ca thut iu tr c th c tnh cho mi bnh nhn i bng
i i i
Y X = . T
, chng ta c th tnh nh hng trung bnh v lch chun ca
i
. Trong thc t,
chng ta khng bit
i
, cho nn phi da vo mt mu. Nu gi c s mu ca
i

l
i
d , chng ta c th c tnh nh hng trung bnh v lch chun ca
i
d . Gi ch
s trung bnh l d v lch chun l s. H s nh hng c th c tnh bng cng
thc:

d
ES
s
=

Ngoi ra, gi r l h s tng quan gia hai o lng. Vi cc thng s ny, s lng c
mu cn thit cho nghin cu l:

( )
( )
2
2 1 C r
n
ES

= [3]


4.1.3 Trong trng hp nghin cu vi hai nhm i tng, mc tiu thng
l so snh hai ch s trung bnh. Gi ch s trung bnh ca nhm 1 v 2 l
1
v
2
. Gi
lch chun ca hai nhm l
1
v
2
. Nu hai lch chun khng khc nhau, h s
nh hng c th c tnh t cng thc [1] nh sau:
1 2
1
ES

=
S lng i tng cho mi nhm (n) cn thit cho nghin cu c th tnh ton nh sau
(gi tr ca hng s C c xc nh t xc sut sai st loi I v II (hay power) trong
Bng 3):
( )
2
2C
n
ES
= [4]

4.1.4 Trong trng hp nghin cu vi hai nhm i tng nhng mc tiu
kim nh nh hng tng ng (equivalence studies). Trong nhiu nghin
cu, chng ta mun nh gi xem hai thut can thip hay iu tr c hiu qu nh nhau.
Gi ch s trung bnh ca nhm 1 v 2 l
1
v
2
. Nu |
1

2
| < d (trong d l
khc bit khng c ngha lm sng), th chng ta tuyn b rng hai thut iu tr c nh
12
hng tng ng. Trong trng ny, h s nh hng s l (ti s dng k hiu H thay
v ES khng nhm ln vi cng thc [1]):


1 2
d
H

=

V s lng c mu cn thit cho mi nhm l:


2
2C
n
H
= [5]

4.2 Cc nghin cu vi tiu ch l bin nh phn (binomial variable)

Trong phn trc chng ta lm quen vi phng php c tnh c mu so
snh hai s trung bnh bng kim nh t. Nhng c nghin cu bin s khng lin tc m
mang tnh nh phn (nh c / khng, sng / cht, dt bnh / khng dt bnh, v.v), ch
s tm lc [d nhin] khng th l s trung bnh, m l t l (proportion). Nhiu nghin
cu m t c mc ch kh n gin l c tnh mt t l. Chng hn nh gii y t
thng hay tm hiu t l lu hnh bnh trong mt cng ng. Trong trng hp ny,
chng ta khng c nhng o lng mang tnh lin tc, nhng kt qu ch l nhng gi tr
nh phn nh c / khng. Phng php c tnh c mu cng khc vi cc phng php
cho cc nghin cu vi bin s lin tc.

Nm 1991, mt cuc thm d kin M cho thy 45% ngi c hi sn sng
khuyn khch con h nn hin mt qu thn cho nhng bnh nhn cn thit. Khong tin
cy 95% ca t l ny l 42% n 48%, tc mt khong cch n 6%! Kt qu ny
[tng i] thiu chnh xc, d s lng i tng tham gia ln n 1000 ngi. Ti
sao? tr li cu hi ny, chng ta th xem qua mt vi l thuyt v c tnh c mu
cho mt t l.

4.2.1 Trong trng hp nghin cu ch c mt nhm i tng, v mc tiu l
c tnh mt t l (k hiu ) v mt bin c lm sng. Qua l thuyt xc sut, chng ta
bit rng nu trong n i tng, c k bin c th c s ca l p = x / n, vi sai s
chun ( ) ( )
1 / SE p p p n = . Khong tin cy 95% ca mt t l [trong qun th] l:
( )
1.96 p SE p .

By gi, th lt ngc vn : chng ta mun c tnh sao khong tin cy
( )
2 1.96 SE p khng qu mt hng s m. Ni cch khc, chng ta mun:
13

( )
1.96 1 / p p n m

Chng ta mun tm s lng i tng n t yu cu trn. Qua cch din t
trn, d dng thy rng:

( )
2
1.96
1 n p p
m
| |

|
\
[6]

Do , s lng c mu ty thuc vo sai s m v t l p m chng ta mun
c tnh. sai s cng thp, s lng c mu cng cao.

4.2.2 Trong trng hp nghin cu c hai nhm i tng, v mc tiu
nghin cu l so snh hai t l. so snh hai t l, phng php kim nh thng dng
nht l kim nh nh phn (binomial test) hay Chi bnh phng (
2
test). Gi hai t l
[m chng ta khng bit nhng mun tm hiu] l
1
v
2
, v gi =
1

2
. Gi thit
m chng ta mun kim nh l = 0.

Nhng trong thc t, chng ta khng bit
1
v
2
, m ch c tnh qua hai t l
1
p v
2
p . L thuyt ng sau c tnh c mu cho kim nh gi thit ny kh rm
r, nhng c th tm gn bng cng thc sau y:

( ) ( ) ( )
( )
2
/ 2 1 1 2 2
2
2 1 1 1 z p p z p p p p
n

+ +
=

[7]
Trong , p = (
1
p +
2
p )/2,
/ 2
z

l tr s z ca phn phi chun cho xc sut /2

(chng hn nh khi = 0.05, th
/ 2
z

= 1.96; khi = 0.01, th

/ 2
z

= 2.57), v z

l tr
s z ca phn phi chun cho xc sut (chng hn nh khi = 0.10, th z

= 1.282; khi
= 0.20 hay power = 0.80, th z

= 0.842).

4.2.3 Trong trng hp nghin cu c hai nhm i tng vi mc tiu
nghin cu l nhm chng minh hai t l tng ng nhau. Vi cc nghin cu
th loi ny, gi thit t ra l nu khc bit gia
1
p v
2
p thp hn d th c th chp
nhn rng
1
v
2
tng ng nhau; nu |
1
p -
2
p | > d, th hai t l khng tng ng
nhau. kim nh gi thit tng ng ny, s lng c mu cn thit cho mi nhm
l:

14

( ) ( )
( )
1 1 2 2
2
1 2
2 1 1 C p p p p
n
p p d
( +

=

[8]

4.3 Cc nghin cu c tnh h s tng quan (coefficient of
correlation)

4.3.1 Trng hp ch c hai bin lin tc. Trong cc nghin cu quan st
(observational studies), k c cc nghin cu mt thi im (cross-sectional studies), i
khi mc tiu chnh l c tnh mt h s tng quan gia hai bin lin tc (chng hn
nh h s tng quan gia tui v nng cholesterol). Gi h s tng quan gia
hai bin l , gi thit t ra l: H
o
: = 0 hoc H
1
0 : . (Nu 0 = , hai bin hon ton
c lp vi nhau, tc khng c mi lin h).

Trong thc t, chng ta khng bit , nhng c th c tnh qua h s tng quan
quan st c l r, c khi cn gi l h s Pearson. Gi thit c th kim nh bng ch
s thng k t nh sau:

3
1
1
log
2
1

+
= n
r
r
t
e


Trong n l s c mu. Ch s t phn phi theo lut phn phi chun vi trung bnh 0
v phng sai 1. Do , vn l tm n sao cho t c ngha thng k, v p s ca n l:


2
3
1 1
log
4 1
e
C
n

= +
(
| | +
( |

\
[9]

4.3.2 Trng hp nghin cu c nhiu bin lin tc. Vi nhng nghin cu
c mt bin ph thuc (dependent variable) v nhiu bin c lp (independent
variables), mc tiu thng l xc nh cc bin c lp c th gii thch bao nhiu
phn trm phng sai ca bin ph thuc. Phng php phn tch chnh l m hnh hi
qui tuyn tnh a bin (multiple linear regression). Trong m hnh ny, ch s phn nh
mi lin h a chiu ny l h s xc nh bi (coefficient of determination), k hiu R
2
.

15
Phng php c tnh c mu cho h s R
2
tng i phc tp, v thng phi s
dng n thut m phng (simulation). Tuy nhin, mt s qui c kh tin cy c th p
dng nh sau:

Vi power = 0.80 v = 0.05, nghin cu cn ti thiu 50 i tng
c tnh R
2
0.23; hay ti thiu 100 c tnh R
2
0.12 [2].

Vi m bin c lp v 1 bin ph thuc, s lng c mu cn thit ti
thiu l n > 104 + m [3].

Vi m 5, s lng c mu cn thit ti thiu l n > 50 + m [4].

4.4 Cc nghin cu c tnh t s nguy c (odds ratio)

Trong cc nghin cu i chng (case-control study), nh nghin cu thng
mun tm hiu mi lin h gia mt yu t nguy c (risk factor) v mt bnh c th. Mi
lin h ny thng c o lng bng odds ratio (OR) m ti tm dch l t s nguy
c (ch khng phi t s chnh m ng nghip trong nc hay s dng). Chng hn
nh nu t s nguy c gia ht thuc l v gy xng l 2, th iu ny c ngha l nhng
ngi ht thuc l c nguy c b gy xng tng khong 2 ln so vi nhng ngi khng
ht thuc l.

Do , c tnh c mu th nghim mt gi thit v mi lin h gia mt yu
t nguy c v bnh thng da vo t s nguy c. c tnh c mu cho cc nghin
cu nh th, nh nghin cu cn phi c trong tay 3 s liu:

T l lu hnh (prevalence) ca yu t nguy c trong mt qun th (gi tt l p);
T s nguy c m nh nghin cu mun bit; v
Cc sai s thng k th hin qua xc sut a v power.

Vi cc s liu trn, cng thc sau y s cung cp cho nh nghin cu mt c tnh
s lng i tng cn thit cho nghin cu (N):

( )
( ) ( )
2
2
1
ln 1
r C
N
r OR p p
+
=

[10]

Trong , r l t s c mu gia hai nhm (v trong cc nghin cu i chng,
khng nht thit hai nhm phi c cng c mu). Nu r = 1 (tc hai nhm c cng s
lng c mu), th cng thc trn s n gin thnh:
16

( ) ( )
2
4
ln 1
C
N
OR p p
=

[11]

4.5 Cc nghin cu vi bin ph thuc l thi gian dn n s kin
(survival studies)

Trong nhiu nghin cu khoa hc, k c nghin cu lm sng, cc nh nghin cu
thng theo di i tng trong mt thi gian, c khi ln n vi mi nm. Bin c xy
ra trong thi gian nh c bnh hay khng c bnh, sng hay cht, v.v l nhng bin
c c ngha lm sng nht nh, nhng thi gian dn n bnh nhn mc bnh hay cht
cn quan trng hn cho vic nh gi nh hng ca mt thut iu tr hay mt yu t
nguy c. Nhng thi gian ny khc nhau gia cc bnh nhn. Chng hn nh thi im
t lc iu tr ung th n thi im bnh nhn cht rt khc nhau gia cc bnh nhn, v
do tiu ch lm sng thng l thi gian sng st ca bnh nhn tnh t khi c iu
tr (hay t khi c chn on bnh).

Nghin cu tiu biu thng c 2 nhm bnh nhn: mt nhm i chng v mt
nhm can thip. Phng php tnh c mu cho cc nghin cu th loi ny kh phc tp,
nhng mt cch tnh n gin cng c th ng dng. Nu thi gian theo di i tng
c nh trc, v t l pht sinh ca hai nhm trong thi gian l
1
p v
2
p , th t s
nguy c (hazards ratio) c th c tnh nh sau [5,6]:

( )
( )
2
1
log
log
p
p
h
e
e
=
V s c mu cn thit cho tng nhm l:


( )
( )( )
2
2 1
2
1 2
1

+
=
h p p
h C
n [12]

4.5 Cc nghin cu v chn on (diagnostic studies)

Nghin cu v chn on thng xoay quanh hai ch s: nhy (sensivity) v
c hiu (specificity) nh trnh by trong Bng 2. Mt phng php chn on c
xem l ng tin cy v c th s dng trong thc hnh lm sng cn phi t nhy v
c hiu ti thiu 0.75 (hay tt hn na l 0.80). Vic pht hin bnh qua chn on cn
ty thuc vo t l lu hnh (prevalence) ca bnh trong mt qun th. Do , phng
php c tnh c mu phi da vo cc ch s ny. Mt cch c th, nh nghin cu cn
phi xc nh cc s liu sau y:
17

Xc sut dng tnh tht (hay nhy k hiu
se
p ) ti thiu l bao nhiu?
Xc sut m tnh tht (hay c hiu k hiu
sp
p ) ti thiu l bao nhiu?
Sai s ca hai xc sut dng tnh tht v m tnh tht l bao nhiu (k hiu w)?
T l lu hnh ca bnh trong qun th l bao nhiu (k hiu
dis
p )

Vi cc thng s ny, s lng c mu c tnh nhy c th c tnh bng
cng thc sau y [7]:

Trc ht, c tnh TP+FN (tc l s dng tnh tht true positive v m tnh
gi - false negative)


( )
2
2
1
w
p p Z
FN TP
se se

= +

Trong ,
2

Z l hng s ca phn phi chun. Nu = 0.05, hng s

2

Z bng
1.96. Sau , c tnh s lng c mu (ti s dng k hiu
se
n ch r y l
s c mu cho nhy):


dis
se
p
FN TP
n
+
= [13]

Tng t, s lng c mu c tnh c hiu c th c tnh qua hai bc
nh sau:

Trc ht, c tnh FP+TN (tc l s dng tnh gi - false positive v m tnh
tht true negative)


( )
2
2
1
w
p p Z
TN FP
sp sp

= +

Sau , c tnh s lng c mu (ti s dng k hiu
sp
n ch r y l s c
mu cho nhy):


dis
sp
p
TN FP
n

+
=
1
[14]

5. V d

18
Trong phn ny, ti s nu nhiu v d v c tnh c mu minh ha cho phn
l thuyt va trnh by trong phn trn. Ti s tp trung cc v d lin quan n nghin
cu lm sng bn c tp ch d theo di.

5.1 c tnh c mu cho mt ch s trung bnh

V d 1 c tnh mt ch s trung bnh: Chng ta mun c tnh chiu cao
n ng ngi Vit, v chp nhn sai s trong vng 1 cm (d = 1) vi khong tin cy 0.95
(tc =0.05) v power = 0.8 (hay = 0.2). Cc nghin cu trc cho bit lch chun
chiu cao ngi Vit khong 4.6 cm. Nh vy, h s nh hng l: ES = 1/4.6 = 0.217,
v hng s C = 7.85. Chng ta c th p dng cng thc [2] c tnh c mu cn thit
cho nghin cu:

( ) ( )
166
217 . 0
85 . 7
2 2
= = =
ES
C
n

Ni cch khc, chng ta cn phi o chiu cao 166 i tng c tnh chiu
cao n ng Vit vi sai s trong vng 1 cm.

Nu sai s chp nhn l 0.5 cm (thay v 1 cm), s lng i tng cn thit l:
( )
2
7.85
664
0.5/ 4.6
n = = . Nu sai s m chng ta chp nhn l 0.1 cm th s lng i
tng nghin cu ln n 16610 ngi! Qua cc c tnh ny, chng ta d dng thy c
mu ty thuc rt ln vo sai s m chng ta chp nhn. Mun c c tnh cng
chnh xc, chng ta cn cng nhiu i tng nghin cu.

V d 2 c tnh c mu cho nghin cu trc sau: Mt loi thuc iu
tr c kh nng tng alkaline phosphatase bnh nhn long xng. lch chun
ca alkaline phosphatase l 15 U/l. Mt nghin cu mi s tin hnh trong mt qun th
bnh nhn Vit Nam, v cc nh nghin cu mun bit bao nhiu bnh nhn cn tuyn
chng minh rng thuc c th alkaline phosphatase t 60 n 65 U/l sau 3 thng iu
tr, vi sai s = 0.05 v power = 0.8.

y l mt loi nghin cu trc sau (before-after study); c ngha l trc
v sau khi iu tr. y, chng ta ch c mt nhm bnh nhn, nhng c o hai ln
(trc khi dng thuc v sau khi dng thuc). Ch tiu lm sng nh gi hiu nghim
ca thuc l thay i v alkaline phosphatase. Trong trng hp ny, chng ta c th
c tnh h s nh hng nh sau:
19
3333 . 0
15
5
= = ES
V l nghin cu trc sau, chng ta cn mt thng tin khc na: l h s tng
quan gia hai ln o lng alkaline phosphatase. Chng ta khng bit h s ny, nhng
c th gi nh n dao ng khong 0.6 n 0.8. Vi h s tng quan 0.6, v s dng
cng thc [3], chng ta c th c tnh s c mu nh sau:

( )
( )
( )
( )
56
3333 . 0
6 . 0 1 85 . 7 2 1 2
2 2
=

=

=
ES
r C
n

Nhng nu h s tng quan l 0.8, th s c mu tr thnh:

( )
( )
28
3333 . 0
8 . 0 1 85 . 7 2
2
=

= n

Ni cch khc, khi h s tng quan cng cao (tc tin cy ca o lng cao), s lng
c mu cng thp.

5.2 c tnh c mu cho so snh hai s trung bnh (hai nhm)

V d 3 Nghin cu so snh hai ch s trung bnh: Mt nghin cu c thit
k th nghim thuc alendronate trong vic iu tr long xng ph n sau thi k
mn kinh. C hai nhm bnh nhn c tuyn: nhm 1 l nhm can thip (c iu tr
bng alendronate), v nhm 2 l nhm i chng (tc khng c iu tr). Tiu ch
nh gi hiu qu ca thuc l mt xng (bone mineral density BMD). S liu t
nghin cu dch t hc cho thy gi tr trung bnh ca BMD trong ph n sau thi k mn
kinh l 0.80 g/cm
2
, vi lch chun l 0.12 g/cm
2
. Vn t ra l chng ta cn phi
nghin cu bao nhiu i tng chng minh rng sau 12 thng iu tr BMD ca
nhm 1 tng khong 5% so vi nhm 2?

Trong v d trn, tm gi tr s trung bnh ca nhm 2 l
2
v nhm 1 l
1
,
chng ta c:
2
= 0.8*1.05 = 0.84 g/cm
2
(tc tng 5% so vi nhm 1), v do , = 0.84
0.80 = 0.04 g/cm
2
. lch chun l = 0.12 g/cm
2
. Nh vy, h s nh hng l:
3333 . 0 12 . 0 / 04 . 0 = = ES . Vi power = 0.90 v = 0.05, hng s C = 10.51, v s c
mu cn thit l:

( ) ( )
189
333 . 0
51 . 10 2 2
2 2
=

= =
ES
C
n
20

Kt qu trn cho bit chng ta cn 190 bnh nhn cho mi nhm (hay 380 bnh
nhn cho cng trnh nghin cu). Trong trng hp ny, power = 0.90 v = 0.05 c
ngha l g ? Tr li: hai thng s c ngha l nu chng ta tin hnh tht nhiu nghin
cu (v d 1000) v mi nghin cu vi 380 bnh nhn, s c 90% (hay 900) nghin cu
s cho ra kt qu trn vi tr s p < 0.05.

V y l th loi nghin cu thng dng, cho nn c ngi v mt biu (xem
biu 1 di y) c tnh c mu cho nhng ai khng thch tnh ton. Biu ny
i hi ngi s dng phi bit c h s nh hng (m biu vit l standardised
difference) v power.


Biu 1. Biu (nomogram) cho c tnh c mu v power cho cc
nghin cu hai nhm. (Ngun: British Medical Journal, 1980, 281,
13361338).
Cch s dng: Ly v d 3, chng ta c standardised difference l 0.33
(tc ES), power = 0.9. nh du 0.33 ct tri, 0.9 ct phi; k ni hai
im nh du bng mt thc thng. im giao cho gia ng k
thng v ct gia chnh l s c mu cn thit cho = 0.05 hay 0.01.
21

V d 4 c tnh c mu chng minh hai thut iu tr c hiu qu
tng ng nhau: Mt nghin cu c thit k chng minh rng hiu qu ca
thuc A v B tng ng nhau. Cc nh nghin cu chn mt xng (BMD) lm
tiu ch lm sng. Nghin cu gm 2 nhm bnh nhn long xng c phn chia ngu
nhin: nhm 1 c iu tr bng A, v nhm 2 c iu tr bng B. Cc nghin cu
trc cho thy sau 6 thng iu tr, A c th tng BMD khong 7%, v B c tc dng
tng BMD khong 4%. Theo cc nghin cu , lch chun ca tng BMD l 10%.
Cc nh nghin cu quyt nh rng nu khc bit v BMD gia hai nhm trong vng
2 g/cm
2
th s xem l hai loi thuc c hiu qu nh nhau. Vn t ra l cn bao nhiu
i tng cho nghin cu vi = 0.05 v power = 0.8?

Vi cc s liu trn, chng ta c th c tnh h s nh hng (xem phn 4.1.4)
nh sau: 1 . 0
10
2 4 7
2 1
=

=

=

d
H . Vi = 0.05 v power = 0.8, hng s C =
7.85 (Bng 3). S lng c mu cn thit cho mi nhm (theo cng thc [5]) l:
( )
1570
1 . 0
85 . 7 2 2
2 2
=

= =
H
C
n
Ni cch khc, cng trnh cn tuyn chn 3140 i tng t c yu cu v
mc tiu ca nghin cu.

5.3 c tnh c mu cho cc nghin cu c tnh h s tng quan

V d 5 Nghin cu tm hiu tng quan. Mi tng quan gia lng
ng trong mu (fasting plasma glucose - FPG) v t trng c th (body mass index
BMI) thng khng nht qun gia cc sc dn, v ngay c mt sc, cng khng nht
qun gia cc qun th. Mt nghin cu c thit k c tnh h s tng quan gia
BMI v FPG. S liu t cc nghin cu trc cho thy h s tng quan thng dao
ng t 0.08 n 0.30. Vn t ra l trong dao ng , nghin cu cn o lng
bao nhiu i tng c kt qu vi tin cy 99% (tc = 0.01) v power = 0.80?

Cng thc [9] c th ng dng c tnh c mu cho nghin cu. Gi d nh
h s tng quan tht l 0.15, v vi = 0.01 v power = 0.80, hng s C = 13.33 (Bng
3). S c mu do l:

499
15 . 0 1
15 . 0 1
log 25 . 0
33 . 11
3
1
1
log 25 . 0
3
2 2
=
(

\
|

+ =
(

\
|

+
+ =
r
r
C
n
22

Ni cch khc, cng trnh ny cn phi tuyn khong 500 i tng t c yu cu
v mc tiu ca nghin cu. Bng sau y cho thy s lng c mu c th dao ng
kh cao ty thuc vo h s tng quan.

Bng 4. S c mu cn thit c tnh h s tng quan vi = 0.01 hay 0.05 v
power = 0.80

S c mu cn thit cho power = 0.80 v H s tng quan
= 0.01 = 0.05
0.05
4527 3138
0.10
1128 783
0.15
499 347
0.20
279 194
0.25
177 123
0.30
121 85
0.35
88 62
0.40
66 47
0.45
51 36
0.50
41 29

5.3 c tnh c mu c tnh mt t l

V d 6 Nghin cu c tnh t l lu hnh: Chng ta mun c tnh t l n
ng ht thuc l Vit Nam sao cho c s khng cao hn hay thp hn 2% so vi t l
tht trong ton dn s. Mt nghin cu trc y cho thy t l ht thuc trong n ng
ngi Vit c th ln n 70%. Cu hi t ra l chng ta cn nghin cu trn bao nhiu
n ng t yu cu trn.

Trong v d ny, chng ta c sai s m = 0.02, p = 0.70, v s lng c mu cn
thit cho nghin cu (theo cng thc [6]) l:

2
1.96
0.7 0.3
0.02
n
| |

|
\


Ni cch khc, chng ta cn nghin cu t nht l 2017. Nu chng ta mun gim sai s
t 2% xung 1% (tc m = 0.01) th s lng i tng s l 8067! Ch cn thm
chnh xc 1%, s lng mu c th thm hn 6000 ngi. Do , vn c tnh c
23
mu phi rt thn trng, xem xt cn bng gia chnh xc thng tin cn thu thp v chi
ph.

5.4 c tnh c mu cho so snh hai t l

V d 7 Nghin cu so snh hai t l pht sinh (incidence rate): Mt th
nghim lm sng i chng ngu nhin c thit k nh gi hiu qu ca mt loi
thuc chng gy xng sng. Hai nhm bnh nhn s c tuyn. Nhm 1 c iu tr
bng thuc, v nhm 2 l nhm i chng (khng c iu tr). Cc nh nghin cu gi
thit rng t l gy xng trong nhm 2 l khong 10%, v thuc c th lm gim t l
ny xung khong 6%. Nu cc nh nghin cu mun th nghim gi thit ny vi sai
st I l = 0.01 v power = 0.90, bao nhiu bnh nhn cn phi c tuyn m cho
nghin cu?

y, chng ta c = 0.10 0.06 = 0.04, v p = (0.10 + 0.06)/2 = 0.08. Vi
= 0.01,
/ 2
z

= 2.57 v vi power = 0.90, z

= 1.28. Do , s lng bnh nhn cn thit

cho mi nhm (theo cng thc [7]) l:

( )
( )
2
2
2.57 2 0.08 0.92 1.28 0.1 0.90 0.06 0.94
1361
0.04
n
+ +
= =

Nh vy, cng trnh nghin cu ny cn phi tuyn t nht l 2722 (1361 x 2) bnh nhn
kim nh gi thit trn.

V d 8 Nghin cu chng minh hai t l tng ng: Quay li vi v d
4 v nghin cu nhm chng minh hai loi thuc A v B c hiu qu nh nhau. Nhng
ln ny, tiu ch lm sng nh gi hiu qu ca thuc l t l pht sinh gy xng ct
sng (incidence of vertebral fracture), ch khng phi l s thay i mt xng. S
liu t cc nghin cu trc y cho thy t l gy xng mi cc bnh nhn c iu
tr bng A l khong 2% v B l 3%. ng trn quan im lm sng, cc nh nghin cu
cho rng nu hai t l khc nhau trong vng 0.5% th c th xem l tng ng. Vn
t ra l cn bao nhiu i tng cho nghin cu t c = 0.05 (tc tin cy
0.95) v power = 0.80?

Vi cc s liu trn (p
1
= 0.02, p
2
= 0.03, v d = 0.005 tc 0.5%) v p dng cng
thc [8], chng ta c th c tnh s c mu cn thit cho mi nhm nh sau:

24
( ) ( ) [ ]
( )
( ) ( ) [ ]
( )
=

+
=

+
=
2 2
2 1
2 2 1 1
005 . 0 03 . 0 02 . 0
97 . 0 03 . 0 98 . 0 02 . 0 85 . 7 2 1 1 2
d p p
p p p p C
n 15291

Do , cng trnh ny cn tuyn 30582 i tng t yu cu ca nghin cu. Nh c
th thy c trong cng thc trn, yu t quan trng trong cch tnh c mu cho nghin
cu loi ny l khc bit d xem l hiu qu hai loi thuc tng ng. S c mu
trn da vo tiu chun khc bit 0.5% kt lun tng ng. Nhng nu tiu
chun d di hn mt cht (nh 1%) th s lng c mu gim xung cho mi nhm
gim xung cn 7646 i tng vn l mt con s ln. So snh vi kt qu c tnh t
v d 4, chng ta thy cng mt mc tiu nghin cu, nhng vn chn tiu ch lm
sng y rt quan trng v c nh hng ln n s c mu.

5.5 c tnh c mu cho mt t s nguy c (odds ratio)

V d 9 Nghin cu bnh-chng (case-control study): Nh nghin cu mun
tm hiu mi lin h gia ht thuc l v nguy c gy xng ct sng (vertebral fracture).
Hai nhm i tng c chn: Nhm 1 l nhng bnh nhn mi gy xng ct sng, v
nhm 2 l nhng i tng khng gy xng, nhng c cng tui, gii vi nhm
bnh nhn. Sau khi c hai nhm i tng, cc nh nghin cu s phng vn xem trong
hai nhm, c bao nhiu ngi ht thuc l. Cc nh nghin cu gi thit rng t s nguy
c gy xng nhng ngi ht thuc l l 2. Nu cc nh nghin cu mun th
nghim gi thit ny vi sai st I l = 0.05 v power = 0.80, bao nhiu i tng cn
phi c tuyn m cho nghin cu? p dng cng thc [11], chng ta c:

( ) ( ) ( )
349
75 . 0 25 . 0 2 ln
85 . 7 4
1 ln
4
2 2
=

=
p p OR
C
n

Cng trnh nghin cu cn phi tuyn t nht l 350 i tng (175 bnh nhn v
175 i chng) kim nh gi thit trn.

5.6 c tnh c mu cho nghin cu v sng st

V d 10 Nghin cu so snh thi gian sng st: Nh cp trong mc 4.5,
nhiu nghin cu y khoa c mc ch so snh thi gian sng st (survival time) gia hai
nhm. Cm t sng st y phi c hiu rng hn, khng ch phn nh t vong v
cn sng, m bao gm thi gian dn n mt s kin lm sng (c th l ung th, t qu,
gy xng, i tho ng, v.v) Chng hn nh nghin cu tm hiu xem mt thuc
mi c th ko di thi gian sng ca bnh nhn hay khng, cc nh nghin cu theo di
2 nhm bnh nhn (nhm 1 c iu tr v nhm 2 l nhm i chng) trong vng 2
25
nm. Theo y vn, t l sng st trong vng 2 nm ca nhm i chng l 25%, cc nh
nghin cu hi vng thuc mi c th ko di thi gian sng cao hn nhm i chng
khong 1.5 ln. t c ngha thng k = 0.05 v power = 0.80, nghin cu cn
bao nhiu bnh nhn?

Trong trng hp ny, chng ta bit c 25 . 0
1
= p , v h = 1.5, do , c th suy
ra t cng thc
( )
( )
5 . 1
ln
25 . 0 ln
2
= =
p
h , v theo : 397 . 0
2
= p . Vi = 0.05 v power =
0.80, hng s C = 7.85. Thay th cc s ny vo cng thc [12], chng ta c s c mu
cho mi nhm l:

( )
( )( )
( )
( )( )
195
1 5 . 1 397 . 0 25 . 0 2
1 5 . 1 85 . 7
1 2
1
2
2
2
2 1
2
=

+
=

+
=
h p p
h C
n .

Nh vy, cng trnh cn phi tuyn chn 390 bnh nhn t cc yu cu v mc ra.

5.7 c tnh c mu cho nghin cu chn on

V d 11 Nghin cu chn on bnh lao phi: Hin nay chn on bnh lao
phi AFB m tnh (soi m trc tip bng phng php Ziehl-Neelsen m tnh) cha c
tiu chun thng nht, ch yu da vo kt qu X quang phi v vic p ng iu tr th
bng thuc chng lao. Vit Nam cc k thut hin i pht hin nhanh vi khun lao ch
tin hnh cc bnh vin ln, cc trung tm thnh ph, cn cc bnh vin c s hay
cp tnh cha c iu kin p dng c. Do , cc nh nghin cu pht trin mt
phng php chn on da vo cn lm sng. Cc nh nghin cu hi vng rng phng
php cn lm sng s c nhy khong 0.80 v c hiu khong 0.95, v mun thit
k nghin cu sao cho hai ch s ny dao ng trn di 5%. Bit rng t l hin hnh
ca bnh lao phi trong cng ng khong 20%. Cu hi t ra l nghin cu cn bao
nhiu i tng t c tin cy thng k 95% (tc = 0.05).

Vi cc s liu trn, chng ta c th c tnh TP+FN:

( ) ( )
( )
=

=

= +
2
2
2
2
05 . 0
20 . 0 80 . 0 96 . 1 1
w
p p Z
FN TP
se se
246

Vi t l hin hnh ca bnh l 20%, s lng c mu cn thit c tnh nhy (theo
cng thc [13]) l: 246 / 0.20 = 1229.

26
Mt khc, cc s liu trn, chng ta c th c tnh FP+TN:

( )
( )
( )
=

=

= +
2
2
2
2
05 . 0
05 . 0 95 . 0 96 . 1
1
w
p p Z
TN FP
sp sp
73

Vi t l hin hnh ca bnh l 20%, s lng c mu cn thit c tnh c hiu
(theo cng thc [14]) l: 73 / (1 0.20) = 91.

Trong trng hp ny, chng ta c hai c tnh kh khc nhau. Nu da vo tiu
ch nhy, nghin cu cn n 1229 i tng, nhng nu ly tiu ch c hiu nghin
cu ch cn 91 i tng. Vn cn li l phi xc nh gia hai ch s nhy v c
hiu, ch s no quan trng hn ly lm tiu ch cho nghin cu. y l mt quyt
nh lm sng cn phi cn nhc trc khi c tnh c mu!

6. Mt s vn v c tnh c mu

iu chnh cho hin tng b cuc. Cc phng php c tnh c mu trnh
by trn y da vo mt gi nh quan trng l nghin cu s tin hnh sung s, tc l
khng c i tng b cuc v s liu thu thp y cho tt c mi i tng. Nhng
trong thc t, chng ta bit rng khng c mt nghin cu no hon ho nh th c. Hin
tng b cuc (withdrawal) rt ph bin trong nghin cu lm sng. V nhiu l do, i
tng khng th tham gia t u n cui cng trnh nghin cu, v phi b cuc. V
b cuc, cho nn s liu ca i tng khng y . Ty theo th loi v tnh can thip
hay xm phm ca cng trnh nghin cu, t l b cuc v khng y s liu c th
dao ng t 10% n 30%.

V th, c tnh c mu cng phi xem xt n kh nng trn bng cch iu
chnh cho t l b cuc. Nu theo l thuyt c tnh, nghin cu cn n i tng, v nu
t l b cuc l q th s lng i tng thc t cn phi l n/(1-q). Chng hn nh trong
v d 8, s lng bnh nhn cn thit cho nghin cu theo l thuyt l 30582 ngi, nu t
l b cuc l 20%, th trong thc t nh nghin cu phi cn tuyn n 30582/(1-0.20) =
34280 bnh nhn.

iu chnh cho trng hp khng cn i gia hai nhm. Cc cng thc tnh
ton c mu ti trnh by trong phn trc cn gi nh rng trong cc nghin cu gm
hai nhm th hai nhm phi c cng s lng i tng. Nhng trong thc t, nhiu
nghin cu (nht l nghin cu bnh chng case-control study) s lng bnh nhn kh
27
m bng s lng i chng, nu bnh thuc vo dng him trong cng ng. V th,
nhm i chng cn phi c nhiu i tng hn nhm bnh.

Trong trng hp mt cn i gia hai nhm, s lng c mu cng cn phi
c iu chnh. Gi tng s c mu l thuyt (ca hai nhm cng li) l N; gi tng s
c mu iu chnh l N*, nu chng ta k vng rng t s c mu ca nhm 1 v nhm 2
l k, th N* c th xc nh bng cng thc sau y:

( )
k
k N
N
4
1
*
2
+
=
D thy rng nu hai nhm cn i (c cng c mu, hay k = 1) th N = N*. Quay li v
d 10, s lng c mu cn thit cho mi nhm l 195 (do N = 390). Nhng nu
chng ta k vng rng s c mu ca nhm 1 phi hn nhm 2 khong 1.5 ln, th tng s
lng i tng cn phi tuyn chn l: N = [390 (1+1.5)
2
] / (41.5) = 406, tc tng
khong 16 i tng so vi c tnh l thuyt.

c tnh c mu l bc u trong nghin cu. Trc khi kt thc bi vit
ny, ti mun nhn c hi nhn mnh mt ln na, c tnh c mu cho nghin cu l
mt bc cc k quan trng trong vic thit k mt nghin cu cho c ngha khoa hc,
v n c th quyt nh thnh bi ca nghin cu. Trc khi c tnh c mu nh nghin
cu cn phi bit trc (hay t ra l c vi gi thit c th) v vn mnh quan tm.

c tnh c mu cn mt s thng s nh cp n trong phn u ca chng,
v nu cc thng s ny khng c th khng th c tnh c. Trong trng hp mt
nghin cu hon ton mi, tc cha ai tng lm trc , c th cc thng s v nh
hng v dao ng o lng s khng c, v nh nghin cu cn phi tin hnh mt
s m phng (simulation) hay mt nghin cu s khi c nhng thng s cn thit.
Cch c tnh c mu bng m phng l mt lnh vc nghin cu kh chuyn su, khng
nm trong ti ca sch ny, nhng bn c c th tm hiu thm phng php ny
trong cc sch gio khoa v thng k hc cp cao hn.

28
Ti liu tham kho:

1. Cohen J. Statistical power analysis for the behavioral science. NY: Academic Press,
1969.

2. Hair JF, Anderson RE, et al. Multivariate data analysis, 5
th
Ed. New Jersey:Prentice-
Hall, 1998.

3. Green SB. How many subjects does it take to do a regression analysis. Multivariat
Behav Res 1991; 26:499-510.

4. Harris RJ. A primer of multivariate analysis, 2
nd
Ed. New York: Academic Press,
1985.

5. Freeman LS. Tables of the number of patients required in clinical trials using the
logrank test. Stat Med 1982; 1:121-129.

6. Lee ET. Statistical methods for survival analysis. Page 320. New York: Wiley, 1992.

7. Jones SJ, Carley S, Harrison M. An introduction to power and sample size estimation.
Emerg Med J 2003; 20:453-458.

Ti liu c thm: Cc cng thc trnh by trong bi vit ny c th tm thy trong cc
sch gio khoa v dch t hc v thng k hc. Ba cun sch sau y c th xem nh loi
sch dn nhp:

1. Machin JM. Biostatistical Methods The Assessment of Relative Risks. New York:
John Wiley & Sons, 2000.

2. Kahn HA, Sempos CT. Statistical Methods in Epidemiology. New York: Oxford
University Press, 1989.

3. Phn tch s liu v to biu bng R - hng dn thc hnh ca ti (tc gi bi
ny) do Nh xut bn Khoa hc v K thut pht hnh, Thnh ph H Ch Minh, 2006.
Trong sch c hng dn cch tnh c mu (v phn tch s liu) bng my tnh qua ngn
ng thng k R.

Ngoi ra, bn c mun tm hiu thm v cc phng php tnh c mu c th tm c
cc bi bo quan trng sau y:

1. Florey CD. Sample size for beginners. BMJ 1993;306(6886):1181-4.

29
2. Day SJ, Graham DF. Sample size and power for comparing two or more treatment
groups in clinical trials. BMJ 1989;299(6700):663-5.

3. Kieser M, Hauschke D. Approximate sample sizes for testing hypotheses about the
ratio and difference of two means. J Biopharm Stat 1999;9(4):641-50.

4. Miller DK, Homan SM. Graphical aid for determining power of clinical trials
involving two groups. BMJ 1988;297(6649):672-6.

5. Campbell MJ, Julious SA, Altman DG. Estimating sample sizes for binary, ordered
categorical, and continuous outcomes in two group comparisons. BMJ
1995;311(7013):1145-8.

6. Sahai H, Khurshid A. Formulae and tables for the determination of sample sizes and
power in clinical trials for testing differences in proportions for the two-sample design: a
review. Stat Med 1996;15(1):1-21.