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LTS. Tr s P trong nghin cu y khoa vn thnh thong c em ra tho lun trn cc
tp san y hc quc t, v ngha ca n vn l mt ti cho chng ta khai thc hiu
r hn. Bi vit sau y mt ln na bn v ngha ca tr s P nhng khng phi ng
trn quan im thng k, m qua ci nhn chn on lm sng. C th cc bn s thy
th v v s tng ng gia nghin cu y khoa v chn on lm sng trong bi vit
ny. Bi vit c ng trn tp san Thng tin Y hc; do , bn c c th tham
kho tp san bit thm chi tit.


ngha ca tr s P trong nghin cu y hc

Nguyn Vn Tun

Trong mt cng trnh nghin cu nh gi hiu qu chng gy xng ca thuc
zoledronate, cc nh nghin cu iu tr 1065 bnh nhn bng zoledronate v 1062 bnh
nhn khng c iu tr bng zoledronate (placebo), v kt qu c trnh by qua mt
on vn quan trng sau y: The rates of any new fracture were 8,6% in the zoledronic
acid group and 13,9% in the placebo group, a 35% risk reduction with zoledronic acid (p
= 0,001); the respective rates of new vertebral fracture were 1,7% and 3,8% (p = 0,02)
[1]. Cu vn trn y gn lin vi tr s p c ngha g?

Khi mt cu hi tng t c em i hi mt nhm bc s chuyn khoa v c
kinh nghim trong nghin cu y hc, c n 85% tr li sai [2]. i a s nhng ngi
c hi hiu rng mt kt lun (v s khc bit) vi tr s p = 0,05 c ngha l kh nng
m kt lun sai l 5%, hay kh nng m kt lun ng l 95% (ly 1 tr cho 0,05).
Nhiu ngi khc th hiu rng mt s khc bit vi tr s P cng nh th mc nh
hng cng c ngha v tin cy ca kt lun cng cao. Nhng rt tic rng c hai
cch hiu ny u sai. iu ng ngc nhin l khng nhng gii lm nghin cu khoa
hc hiu sai, m ngay c cc nh nghin cu c kin thc thng k kh nh dch t hc
cng hiu sai. Tht ra, mt s nh thng k chuyn nghip cng hiu sai ngha ca tr
s P bi v mt s sch gio khoa gii thch hoc l sai, hoc khng r rng!

Trong bi vit ngn ny, ti s gii thch ngha tht ca tr s P, bn qua nhng
khim khuyt ca n, v gii thiu mt trng phi suy lun khoa hc c ch cho nghin
cu lm sng.

1. Tr s P v trit l phn nghim (falsificationism)

Khi c cc bi bo khoa hc trn cc tp san y hc, chng ta thng hay gp
nhng tr s P. Mt s khc bit vi tr s p < 0,05 thng c hiu l s khc bit
c ngha thng k (statistically significant); ngc li, khi p > 0,05 chng ta thng
hiu rng s khc bit khng c ngha thng k, khng ng k, hay do ngu nhin.
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 2
Tuy nhin, cch hiu P [l mt xc sut phi iu kin] nh th rt sai lm. Tr s P l mt
xc sut c iu kin. ngha ca tr s P gn lin vi trit l phn nghim
(falsificationism) trong khoa hc. Do , trc khi bn v ngha ca tr s P, thit
tng chng ta cn phi hiu qua v trit l phn nghim.

Mt gi thuyt c xem l mang tnh khoa hc nu gi thuyt c kh nng
phn nghim. Theo Karl Popper [3], nh trit hc khoa hc, c im duy nht c
th phn bit gia mt l thuyt khoa hc thc th vi ngy khoa hc (pseudoscience) l
thuyt khoa hc lun c c tnh c th b bc b hay kh nng phn nghim
(falsified) bng nhng thc nghim n gin. ng gi l kh nng phn nghim
(falsifiability) [4]. Php phn nghim l phng cch tin hnh nhng thc nghim
khng phi xc minh m ph phn cc l thuyt khoa hc, v c th coi y nh l
mt nn tng cho khoa hc thc th. Chng hn nh gi thuyt [n gin] Tt c cc
qu u mu en c th b bc b nu chng ta quan st c mt con qu mu .
Hay, gi thuyt vi khun V. cholerae gy bnh dch t c th bc b nu c mt bnh
nhn dch t khng nhim vi khun V. cholerae.

ng trn phng din khoa hc, c hai m hnh thc t tip cn l thuyt
phn nghim: l m hnh kim nh thng k v m hnh kim nh gi thuyt. Rt
nhiu sch gio khoa thng k v khoa hc c vit ra, nhng rt tic, nhiu tc gi
khng gii thch hay khng phn bit c hai m hnh ny. C tc gi thm ch cn
nhm ln khi din dch, v cng chnh l mt trong nhng nguyn nhn dn n tnh
trng hiu lm ngha ca tr s P. Trong phn ny, ti s gii thch ngn gn v cung
cp ti liu tham kho ca hai m hnh bn c c th hiu qua v nghin cu thm.

1.1 Fisher v m hnh kim nh ngha thng k

Trit l phn nghim rt ph bin v tr thnh mt m hnh gii thch s tin
b ca khoa hc. Chu nh hng bi trit l ny, Ronald A. Fisher (1890 1962), mt
nh di truyn hc ngi Anh v cng l cha ca nn thng k hc hin i, xut
mt phng php nh lng phn nghim mt gi thuyt khoa hc. ng gi phng
php ny l Test of Significance [5-6] (ti tm dch l: phng php kim nh
ngha thng k). Fisher quan nim rng thng k l mt b phn quan trng ca phng
php suy lun theo php qui np (inductive inference), tc l phng php suy lun da
vo quan st t cc mu (sample) v khi qut cho mt qun th (population). Phng
php kim nh ngha thng k c tin hnh theo 3 bc nh sau:

Bc 1, pht biu mt gi thuyt v hiu (null hypothesis). Gi thuyt v hiu l
gi thuyt ngc li vi gi thuyt m nh nghin cu mun kim nh. Chng
hn nh nu gi thuyt iu tr bng thuc zoledronate lm gim nguy c t vong
(nhm c iu tr bng zoledronate c t l t vong thp hn nhm gi dc),
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 3
th gi thuyt v hiu s pht biu l t l t vong bnh nhn c iu tr bng
zoledronate bng vi nhm gi dc. Gi gi thuyt v hiu l H0.

Bc 2, thu thp d liu lin quan n gi thuyt. Trong v d trn, s liu s l
s trng hp t vong. Gi d liu l D.

Bc 3, c tnh xc sut quan st d liu D nu gi thuyt H0 ng. Ni cch
khc v vit theo ngn ng ton, bc ny c tnh P(D | H0). y chnh l tr
s P (p-value).

Fisher ngh bo co tr s P mt cch chnh xc. Tc l khng c nhng cch
vit nh p < 0,05 hay p > 0,01 m phi l p = 0,043 hay p = 0,002. Fisher cn ngh
rng nu tr s p thp hn 0,05 th gi thuyt H0 (v hiu) khng ph hp vi s liu
quan st c. i vi Fisher, khng c chuyn bc b gi thuyt hay chng minh
gi thuyt m ch c s liu c ph hp, c nht qun vi gi thuyt hay khng m thi.
Quan im ny chu nh hng m ca trit l phn nghim ca Popper, v theo trit l
ny, chng ta khng th chng minh bt c mt gi thuyt no, m ch c th bc b
(disprove) mt gi thuyt bng d liu quan st c.

V d 1. C th minh ha cho cc bc trn bng mt v d nh sau: chng ta c
10 bnh nhn, mi bnh nhn c iu tr bng 2 loi thuc (A v B). Sau khi theo di
mt thi gian, c 8 bnh nhn m hiu qu ca thuc A tt hn thuc B. Kt qu ny c
ph hp vi gi thuyt thuc A tt hn thuc B?

tr li cu hi v cng l kim nh gi thuyt trn, chng ta pht biu mt gi
thuyt v hiu: nu hai loi thuc ny c hiu qu nh nhau, th s c 5 bnh nhn vi kt
qu A tt hn B, v 5 bnh nhn vi kt qu B tt hn A. Gi l xc sut m kt qu
thuc A tt hn thuc B. Gi thuyt v hiu ny cng c ngha l = 0,5. Nu gi
thuyt v hiu ny ng (tc = 0,5), chng ta c th tnh ton xc sut quan st k bnh
nhn (k = 0, 1, 2, 3, , 10) vi kt qu A tt hn B theo lut phn phi nh phn nh sau:

( ) ( )( ) ( )
k k
k
k P

= =
10 10
5 , 0 1 5 , 0 5 , 0 |

V kt qu c th trnh by trong bng sau y:

Bng 1. Xc sut quan st k bnh nhn (trong s 10 bnh
nhn) vi kt qu A>B nu gi thuyt v hiu ( = 0,5)
ng

k = Pr(k | =0,5)
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 4
0 0,0009765625
1 0,009765625
2 0,04394531
3 0,1171875
4 0,2050781
5 0,2460938
6 0,2050781
7 0,1171875
8 0,04394531
9 0,009765625
10 0,0009765625
P(k 8) 0,054687


C nhin, tng s xc sut k = 0, 1, 2, , 10 phi bng 1. Theo kt qu trn, nu khng
c s khc bit v hiu qu ca hai thuc, xc sut m chng ta quan st 8 bnh nhn vi
kt qu A>B l khong 4,39%. Din dch tng t, chng ta c tnh rng xc sut vi 9
bnh nhn kt qu A>B l 0,97%, v xc sut tt c 10 bnh nhn vi kt qu A>B l
0,097%. Xc sut m ti thiu 8 bnh nhn vi kt qu A>B l 0,055 hay 5,5%. Vit
theo k hiu ton: P(k 8) = 0,0547. y chnh l tr s P.

S dng tiu ch 0,05, chng ta c th ni rng d 80% (8 trn 10) bnh nhn vi
kt qu A>B, chng ta vn cha c y bng chng khng nh rng kt qu ny
nht qun vi gi thuyt thuc A tt hn B.

1.2 Neyman v Pearson v m hnh Kim nh gi thuyt

Jerzy Neyman (1894 1981) l mt nh ton hc xut sc gc Ba Lan v Egon
Pearson (1895 1980) l mt nh thng k hc (con ca gio s Karl Pearson, cha ca
l thuyt Chi-square v h s tng quan) cng lc vi Fisher, pht trin mt phng
php rt khc vi Fisher, m hai ng gi l Test of Hypothesis (Kim nh gi thuyt)
[7]. Neyman v Pearson bc b khi nim suy lun theo qui np; hai ng ngh rng thng
k hc l mt phng php hay c ch hng dn chng ta i n mt quyt nh
ng v lu v di. Ni cch khc, Neyman v Pearson cho rng phng php ca Fisher
v ngha!

Mt cch n gin, m hnh kim nh gi thuyt ca Neyman v Pearson c th
thc hin qua cc bc nh sau:

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 5
Bc 1, pht biu gi thuyt chnh (H1) v gi thuyt v hiu (H0).

Bc 2, quyt nh mc v c th chp nhn c v c tnh c mu cn
thuyt. l xc sut bc b gi thuyt H1 nhng l gi thuyt ng. l xc
sut bc b H0 trong khi H0 ng.

Bc 3, thu thp d liu lin quan n gi thuyt.

Bc 4, nu d liu nm trong khong bc b gi thuyt H0, th chp nhn gi
thuyt H1; nu khng th chp nhn gi thuyt H0. Ch rng chp nhn mt
gi thuyt khng c ngha l chng ta tin vo gi thuyt , m ch c ngha l
chng ta hnh ng vi iu kin l gi thuyt ng.

Nguyn l ca m hnh Neyman v Pearson l chng ta da vo d liu chn
mt gi thuyt sao cho v lu v di chng ta khng qu sai. Chnh v th m ngy nay
chng ta thng chn = 5% v = 10% n 20%.

Fisher bc b hon ton m hnh ca Neyman v Pearson [8]. ng cho rng l
mt m hnh v duyn. Fisher nho bng rng cc nh ton hc (m ch Neyman v
Pearson) chng hiu g v thc nghim v ra mt m hnh qu phi thc t. Trong
nhng nm sau (thp nin 1930s) cng ng thng k hc chng kin mt cuc tranh
lun dai dng v i khi nng bng gia Fisher v Neyman-Pearson trn cc tp san
thng k hc Anh. Fisher tuy l mt ngi thng minh tuyt vi, mt nh t tng vi
nhng suy ngh tru tng, nhng li l mt ngi rt kh tnh v c khi hp hi. S hp
hi ca Fisher th hin ch ng s dng chc quyn khoa bng ca mnh gy kh
khn cho Neyman n ni ng ny chu khng ni v phi di c sang M v sau ny tr
thnh gio s ti trng i hc Berkeley. Sau ny, Neyman c lch s ghi nhn l
mt nh thng k hc xut sc c cng cc k to ln cho khoa hc hin i, snh vai cng
cc i th trong khoa hc hin i. Nc M qu tht l mi trng cho ng thi th ti
nng!

1.2 Mt m hnh hn hp

Tr tru thay, my mi nm sau, hai m hnh ca Fisher v Neyman-Pearson
c hun c thnh mt m hnh tng hp m chng ta ng dng ngy nay trong
nghin cu y hc. M hnh ny s dng kt qu kim nh thng k ca Fisher i n
quyt nh chp nhn hay bc b gi thuyt v hiu H0 hay gi thuyt chnh H1 theo m
hnh ca Neyman v Pearson. Tiu biu cho m hnh ny l nghin cu lm sng i
chng ngu nhin (randomized controlled clinical trial hay RCT). Theo , mt nghin
cu lm sng c tin hnh theo cc bc nh sau:

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 6
Bc 1, nh ngha mt gi thuyt v hiu v mt gi thuyt chnh. Th d trong
mt nghin cu lm sng, gm hai nhm bnh nhn: mt nhm c iu tr bng
thuc A, v mt nhm c iu tr bng placebo, nh nghin cu c th pht
biu gi thuyt v hiu rng hiu nghim thuc A tng ng vi placebo.

Bc 2, xc nh xc sut (cn gi l sai s loi I) v (cn gi l sai s loi
II), v c tnh c mu da vo hai xc sut ny.

Bc 3, thu thp d liu lin quan n gi thuyt. Gi d liu l D.

Bc 4, s dng phng php kim nh ngha thng k ca Fisher c tnh xc
sut P(D | H0). Gi tr s ny l P.

Bc 5, nu P < 0,05, bc b gi thuyt H0. Ch , bc b H0 khng c ngha l
chng ta chp nhn gi thuyt H1.

V d 2. C th minh ha cho cc bc trn bng mt v d v nghin cu hiu
qu ca thuc zoledronate trong vic phng chng long xng [1]. Vi gi thuyt rng
thuc c hiu nghim gim nguy c gy xng, cc nh nghin cu so snh t l gy
xng gia hai nhm bnh nhn: nhm 1 c iu tr bng zoledronate v nhm 2 l
nhm gi c (nhn calcium v vitamin D). Bt u bng cch xc nh = 0,05 v
= 0,80, cc nh nghin cu c tnh s lng bnh nhn cn thit. Sau ba nm thu thp
s liu, kt qu c th tm lc trong bng s liu sau y:

Bng 2. Nguy c gy xng bnh nhn c iu tr bng zoledronate v
placebo

Ch s Zoledronate Placebo Tr s P
S bnh nhn 1065 1062
S gy xng 92 139
T l gy xng 8,6% 13,9 0,001

Bi v tr s P thp hn mc (0,05) m cc nh nghin cu ra t lc u
(trc khi thu thp s liu); cho nn, cc nh nghin cu kt lun rng s khc bit v t
l gy xng gia hai nhm (8,6% vs 13,9%) c ngha thng k. Tt nhin, tr s P
trn khng c ngha l nghin cu chng minh rng thuc zoledronate c hiu qu
gim nguy c gy xng. N c ngha l nu tht s thuc zoledronate khng c hiu
qu gim nguy c gy xng th xc sut m cc nh nghin cu quan st cc s liu trn
(13,9% so vi 8,6%) l 0,001.

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 7
2. Vn ca tr s P

C l ni khng ngoa rng tr s P l mt con s ph bin nht trong khoa hc t
khong 100 nm qua [9]. Hu ht cc bi bo khoa hc u trnh by tr s P nh hm
nng cao tnh khoa hc v tin cy ca bi bo. Tuy nhin, ngay t lc mi ra i, tr
s P b ph bnh d di. C ngi cho rng vic ng dng tr s P trong suy lun khoa
hc l mt bc li, l mt s thoi ha ca khoa hc, nn ngh khng s dng tr s
ny trong nghin cu khoa hc. Nhng d chu nhiu ch trch v ph bnh, ng dng
phng php kim nh gi thuyt v tr s P vn cng ngy cng ph bin, n gin v
chng ta cha c mt phng php khc tt hn, hay hp l hn, hay n gin hn.
Trong phn ny, ti s khng im qua tt c cc ph bnh tr s P (v lm nh th cn
mt cun sch), m ch nu mt s vn chng ta cn lu khi din dch tr s P.


2.1 Vn logic

Nh qua minh ha trn, tr s P khng cho chng ta bit g v s kh d ca mt
gi thuyt, bi v n l mt xc sut c iu kin. Tr s P cho chng ta bit xc sut ca
d liu (data) nu mt gi thuyt l ng. Ci khim khuyt ln nht ca tr s P l n
thiu tnh logic. Tht vy, nu chng ta chu kh xem xt li v d trn, c th khi qut
tin trnh ca mt nghin cu y hc (da vo tr s P) nh sau:

ra mt gi thuyt chnh v hiu (H0)
T gi thuyt v hiu, ra mt gi thuyt chnh (H1)
Tin hnh thu thp d liu (D)
Phn tch d kin: tnh ton xc sut D xy ra nu H0 l tht. Ni theo ngn
ng ton xc sut, bc ny chnh l bc tnh ton tr s P hay P(D | H0).

V th, con s P c ngha l xc sut ca d liu D xy ra nu (nhn mnh: nu)
gi thuyt v hiu H0 l ng. Nh vy, con s P khng trc tip cho chng ta mt
nim g v s tht ca gi thuyt chnh H1; n ch gin tip cung cp bng chng
chng ta chp nhn gi thuyt chnh v bc b gi thuyt v hiu.

Logic ng sau ca tr s P c th c hiu nh l mt qui trnh chng minh o
ngc (proof by contradiction):

Mnh 1: Nu gi thuyt v hiu ng, th s kin ny khng th xy ra;
Mnh 2: S kin xy ra;
Mnh 3 (kt lun): Gi thuyt v hiu khng th ng.

Nu cch lp lun trn kh hiu, chng ta th xem mt v d c th nh sau:

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 8
Nu ng Tun b cao huyt p, th ng khng th c triu chng rng tc (hai
hin tng sinh hc ny khng lin quan vi nhau, t ra l theo kin thc y
khoa hin nay);
ng Tun b rng tc;
Do , ng Tun khng th b cao huyt p.

Tr s P, do , gin tip phn nh xc sut ca mnh 3. V cng chnh l
mt khim khuyt quan trng ca tr s P, bi v n c tnh mc kh d ca d liu,
ch khng ni cho chng ta bit mc kh d ca mt gi thuyt. iu ny lm cho
vic suy lun da vo tr s P rt xa ri vi thc t, xa ri vi khoa hc thc nghim.
Trong khoa hc thc nghim, iu m nh nghin cu mun bit l vi d liu m h c
c, xc sut ca gi thuyt chnh l bao nhiu, ch h khng mun bit nu gi thuyt
o l s tht th xc sut ca d liu l bao nhiu. Ni cch khc v dng k hiu m t
trn, nh nghin cu mun bit P(H1 | D), ch khng mun bit P(D | H0) hay P(D | H1).


2.2 ngha thng k khng tng ng vi ngha lm sng

Mt sai lm rt ph bin trong gii y khoa l xem mt khc bit c ngha thng
k (statistical significance) tng ng vi ngha lm sng (clinical significance).
C th xem tr s P c tnh ton t t s ca tn hiu (signal, mc khc bit gia hai
nhm) v nhiu (noise hay dao ng ca mu). Gi T l kim nh thng k, S l tn
hiu, v E l nhiu, tng trn c th m t nh sau:

S
T
E
=

Khi s lng c mu tng v nu S bt bin th T s tng, tc c c hi t ngha thng
k. iu ny c ngha l chng ta c th gim E ti a bng cch tng s lng c mu,
v n cng c ngha l mt khc bit rt nh chng c ngha g trong thc t nhng vn
c th c ngha thng k. Ngc li, mt khc bit hay nh hng (effect) ln, nhng
nu s lng c mu khng y khng th t c ci chun c ngha thng k
(tc p > 0,05).

Bng 3 sau y trnh by 4 nghin cu (tng tng) vi s c mu khc nhau, t
20 n 2.000.000 bnh nhn. Ct Kt qu trnh by s bnh nhn c iu tr dt
bnh v s trong ngoc l phn trm. Gi thuyt v hiu l xc sut kt qu 0,5 (tc
50%). Tt c 4 nghin cu u c tr s P = 0,041. Nh c th thy qua bng ny,
nghin cu 1 c t l nh hng cao v c ngha lm sng (75%), v ch vi 20 bnh
nhn, cc nh nghin cu c th bc b gi thuyt H0. Nhng nghin cu 4, mc nh
hng rt thp (ch 50,07%, tc ch cao hn gi thuyt v hiu 0,07%) nhng vn c
ngha thng k v s c mu qu ln !
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 9

Bng 3. nh hng ca c mu n tr s P

Nghin cu S lng i
tng
Kt qu iu tr
thnh cng (%)
Tr s P
1 20 15 (75%) 0,041
2 200 114 (57%) 0,041
3 2000 1.046 (52,5%) 0,041
4 2.000.000 1.001.445
(50,07%)
0,041

Trong thc t, c rt nhiu nghin cu m khc bit gia hai nhm rt nh,
nhng vn c ngha thng k [10-11]. iu ng quan tm l kt qu c ngha thng
k nh th c cc nh nghin cu din dch vi hm c ngha lm sng.

Ngc li, c nhng nghin cu m kt qu c ngha lm sng nhng v khng
t ci chun p < 0,05, nn cc nh nghin cu li din dch rng khng c ngha lm
sng! Chng hn nh mt nghin cu v hiu qu ca b sung vitamin C v E ph n
mang thai [12], cc nh nghin cu kt lun rng Supplementation with vitamin C and E
during pregnancy does not reduce the risk of serious outcomes in their infants (B sung
vitamin E v E khng lm gim cc triu chng lm sng nghim trng). Nhng khi xt
qua s liu thc t th thy tr em m m c b sung vitamin C v E, t l vi triu
chng lm sng gim n 21% (p = 0,06). Ch v p = 0,06 m cc nh nghin cu c xu
hng din dch sai kt qu, v sai lm ny rt nghim trng!

2.2 Vn kim nh nhiu gi thuyt
Nh ni trn, nghin cu y hc l mt qui trnh kim nh gi thuyt. Trong
mt nghin cu, t khi no chng ta kim nh ch mt gi thuyt duy nht, m rt nhiu
gi thuyt cng mt lc. Chng hn nh trong mt nghin cu v mi lin h gia
vitamin D v nguy c gy c xng i, cc nh nghin cu c th phn tch mi lin h
gia vitamin D v mt xng (bone mineral density), gia vitamin D v nguy c gy
xng theo tng gii tnh, tng nhm tui, hay phn tch theo cc c tnh lm sng ca
bnh nhn, v.v Mi mt phn tch nh th c th xem l mt kim nh gi thuyt.
y, chng ta phi i din vi vn nhiu gi thuyt (multiple tests of hypothesis hay
cn gi l multiple comparisons).
Vn l nh sau: nu chng ta kim nh mt gi chng ta chp nhn mt sai st
5% (gi d chng ta chp nhn tiu chun p = 0,05 tuyn b c ngha hay khng c
ngha thng k). Ni cch khc, s tht l khng thuc c hiu qu sai, nhng kt qu
kim nh thng k cho ra kt qu c ngha thng k, v chng ta chp nhn rng s
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 10
kin ny c th xy ra vi tn s 5%. Vn t ra l trong bi cnh kim nh nhiu gi
thuyt l nh sau: nu trong s n th nghim, chng ta tuyn b k th nghim c
ngha thng k (tc l p<0,05), th xc sut c t nht mt gi thuyt sai l bao
nhiu?
tr li cu hi ny chng ta s bt u bng mt v d n gin. Mi kim
nh chng ta chp nhn mt xc sut sai lm l 0,05. Ni cch khc, chng ta c xc sut
ng l 0,95. Nu chng ta th nghim 3 gi thuyt, xc sut m chng ta ng c ba [d
nhin] l: 0,95 x 0,95 x 0,95 = 0,8574. Nh vy, xc xut c t nht mt sai lm trong ba
tuyn b c ngha thng k l: 1 0,8574 = 0,1426 (tc khong 14%).
Ni chung, nu chng ta th nghim n gi thuyt, v mi ln th nghim chng ta
chp nhn mt xc sut sai lm l p, th xc sut c t nht 1 sai lm trong n ln th
nghim l ( )
n
p 1 1 . Khi s ln kim nh l n = 10 v p=0,05 th xc sut c t nht
mt kt lun sai lm ln n 40%!
Bi hc rt ra t cch l gii trn l nh sau: nu chng ta c mt bi bo khoa
hc m trong nh nghin cu tin hnh nhiu th nghim khc nhau vi cc kt qu tr
s p < 0,05, chng ta c l do cho rng xc sut m mt trong nhng ci-gi-l
significant (hay c ngha thng k) rt cao. Chng ta cn phi d dt vi nhng
kt qu phn tch nh th.
i vi mt ngi lm nghin cu, ngha ca vn th nghim nhiu gi
thuyt l: khng nn cu c. Xin ni thm v khi nim cu c trong khoa hc. Hy
tng tng, mt nh nghin cu mun tm hiu hiu qu ca mt thut iu tr mi cho
cc bnh nhn au khp. Sau khi xem xt cc nghin cu cng b trong y vn, nh
nghin cu quyt nh tin hnh mt nghin cu trn 300 bnh nhn: phn na c iu
tr bng thut mi, phn na ch s dng gi dc. Sau thi gian theo di, thu thp d
liu, nh nghin cu phn tch v pht hin s khc bit gia hai nhm khng c ngha
thng k. Ni cch khc, thut iu tr khng c hiu qu. Nh nghin cu khng chu
u hng, nn tm cho c mt kt qu c ngha thng k: chia bnh nhn thnh
nhiu nhm theo tui (trn 50 hay di 50), theo gii tnh (nam hay n), thnh phn
kinh t (c thu nhp cao hay thp), v thi quen (chi th thao hay khng). Tnh chung,
nh nghin cu c 16 nhm khc nhau, v c th kim nh 16 gi thuyt. Nh nghin
cu khm ph thut iu tr c ngha thng k trong nhm ph n tui trn 50 v c
thu nhp cao. V, kt qu trn c cng b. l mt qui trnh lm vic m gii
nghin cu khoa hc gi l fishing expedition (mt chuyn i cu c). Tt nhin, mt
kt qu nh th khng c gi tr khoa hc v khng th tin c. (Vi 16 th nghim
khc nhau v vi p = 0,05, xc sut m mt th nghim c kt qu significant ln n
55%, do chng ta chng ngc nhin khi thy c mt con c c bt!)
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 11
cho kt qu tr s P c ngha nguyn thy ca n trong bi cnh th nghim
nhiu gi thuyt, cc nh nghin cu ngh s dng thut iu chnh Bonferroni (tn
ca mt nh thng k hc ngi tng ngh cch lm ny). Theo ngh ny, trc
khi tin hnh nghin cu, nh nghin cu phi xc nh r gi thuyt no l chnh, v gi
thuyt no l ph. Ngoi ra, nh nghin cu cn phi ra k hoch s th nghim bao
nhiu gi thuyt trc khi phn tch d liu. Chng hn nh nu nh nghin cu c k
hoch th nghim 20 so snh v mun gi cho tr s p 0,05, th thay v da vo 0,05 l
tiu chun tuyn bsignificant, nh nghin cu phi da vo tiu chun 0,0025 (tc
ly 0,05 chia cho 20) tuyn b significant. Ni cch khc, ch khi no mt kt qu
c tr s p thp hn 0,0025 (hay ni chung l p/n) th nh nghin cu mi c quyn
tuyn b kt qu c ngha thng k.

3. Tr s P v chn on y khoa

C mt mi tng quan gia nghin cu khoa hc v chn on y khoa, m ti
thy gii y hc t khi no n gii thch v ngha ca tr s P:

Hai lnh vc u c cng mc ch: i tm ci cha c bit. Trong nghin cu
y hc chng ta tm mt mi lin h (hay c tnh / nh gi hiu qu ca mt
thut can thip), cn trong chn on chng ta mun bit bnh nhn c bnh hay
khng c bnh.

Nghin cu y hc s dng thng k hc lm phng php kim nh, cn chn
on y khoa s dng xt nghim lm sng hay sinh ha nh bnh. Do ,
phng php kim nh thng k tng ng vi phng php xt nghim sinh
ha / lm sng.

Trong nghin cu y hc, thuc thc s khng hiu qu, nhng kt qu phn tch
thng k cho rng c ngha thng k. Trong chn on y khoa, bnh nhn
khng c bnh, nhng kt qu xt nghim l dng tnh.

Tng t, trong nghin cu y hc, thuc thc s c hiu qu, nhng kt qu phn
tch thng k cho rng khng c ngha thng k. Trong chn on y khoa, bnh
nhn c bnh, nhng kt qu xt nghim l m tnh.

Do , hiu ngha v cch din dch tr s P, chng ta cn bn qua v qun
trit ngha ca mt kt qu chn on y khoa. Ti s ly v d chn on ung th lm
v d. bit mt ph n b ung th v hay khng, cch chnh xc nht l qua gii phu,
hay trong trng hp nhng ngi cht, l qua gio nghim t thi. Nhng gii phu l
mt thut mang tnh xm phm cao, v tn km. Do , cc nh khoa hc pht trin
nhiu phng php c th chn on ung th m khng cn n gii phu bit bnh
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 12
trng ca ca bnh nhn. Trong trng hp ung th v, mt phng php cng ngh cao
l chp quang tuyn X, hay cn gi l mammography.

Kt qu ca vic xt nghim bng quang tuyn X c th l dng tnh (positive,
s vit tt l +ve), hay m tnh (negative, -ve). Mt kt qu dng tnh c ngha rng
bnh nhn c th b ung th v, v mt kt qu m tnh cho bit bnh nhn c th khng
b ung th v. (Hai ch c th y rt quan trng, v n ni ln mt s bt nh trong
vic chn on ung th v bng quang tuyn X). Do , i chiu kt qu th nghim
ca X-quang tuyn vi thc trng ca bnh nhn, chng ta c 4 kh nng:

Chn on ung th v Nghin cu y hc
K : bnh nhn tht s ung th H1 : gi thuyt chnh l ng
N : bnh nhn khng b ung th H0 : gi thuyt v hiu ng
+ve : kt qu xt nghim dng tnh S (P<0,05) : c ngha thng k
-ve : kt qu xt nghim m tnh NS (P>0,05) : khng c ngha thng k
Kh nng Kh nng

Bnh nhn qu tht b ung th v, v kt
qu xt nghim l dng tnh; trong chn
on y khoa, trng hp ny c gi l
dng tnh tht hay nhy (danh t
chuyn mn ting Anh gi l sensitivity).
Pht biu theo ngn ng xc sut, y
chnh P(+ve | K).

Gi thuyt H1 ng (chng hn nh thuc
c hiu nghim), v kt qu phn tch c
ngha thng k. y l trng hp m cc
nh nghin cu cp n l power. Ni
theo xc sut: P(H1 | S) = power, tng
ng vi dng tnh tht.

Bnh nhn qu tht b ung th, nhng kt
qu th nghim li m tnh; y l trng
hp cn c gi ngn gn l m tnh gi
(false negative) hay P(-ve | K).

Gi thuyt H1 ng, nhng kt qu phn
tch khng c ngha thng k. y l
trng hp m cc nh nghin cu cp
n l type II error (sai st loi II). Ni
theo xc sut: P(NS | H1), tng ng vi
m tnh gi.

Bnh nhn khng b ung th, v kt qu
th nghim l m tnh; y l trng hp
ca m tnh tht hay c hiu
(specificity) hay P(-ve | N)

Gi thuyt H0 ng (tc thuc khng c
hiu qu), v kt qu phn tch cng khng
c ngha thng k. y l trng hp
m cc nh nghin cu cp n l
confidence level. Ni theo ngn ng xc
sut: P(NS | H0), tng ng vi m tnh
tht.

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 13
Bnh nhn qu tht khng c ung th,
nhng kt qu th nghim l dng tnh;
y l trng hp ca dng tnh gi
(false positive) hay P(+ve | K).
Gi thuyt H0 ng, nhng kt qu phn
tch c ngha thng k. y l trng
hp m cc nh nghin cu cp n l
type I error (sai st loi I). Ni theo xc
sut: P(S | H0), tng ng vi dng
tnh gi.

ngha ca nhy, c hiu, dng tnh gi, m tnh gi c th hiu qua cc
gii thch sau y:

nhy (hay sensitivity, dng tnh tht) c th din gii nh sau: nu 100
bnh nhn mc bnh u i xt nghim, c bao nhiu ngi c kt qu dng
tnh.

c hiu (specificity, m tnh tht) tr li cu hi sau y: nu 100 ngi
khng mc bnh u i xt nghim, c bao nhiu ngi c kt qu m tnh.

Do , dng tnh gi (false positive) l s ngi khng mc bnh nhng c
kt qu xt nghim dng tnh.

Tng t, m tnh gi (false negative) l s ngi mc bnh nhng c kt qu
xt nghim m tnh.

Mt phng php chn on hon ho l phng php c t l dng tnh tht v
m tnh tht 100% (tc t l dng tnh gi v m tnh gi l 0%). Nhng trong thc t,
khng c phng php th nghim no l hon ho c. Thc vy, bt c mt phng
php th nghim y khoa no, k c quang tuyn X, cng u c, khng t th nhiu, t l
dng tnh gi v m tnh gi. Hai sai st ny l u mi ca nhiu vn trong vic
khm nghim ung th v.

Do , mt kt qu xt nghim dng tnh khng c ngha l bnh nhn mc
bnh ung th v. iu ny ng, bi v kt qu xt nghim c phn nh sai thc trng
ca bnh. Nn nh rng cc ch s nh nhy, c hiu ch cho chng ta bit
chnh xc ca phng php xt nghim, ch khng cho bit kh nng mc bnh. y l
mt iu rt quan trng m rt tic rt nhiu bc s khng hay cha nhn thc c.

Tng t, trong nghin cu y hc, mt kt qu c ngha thng k (p<0,05)
khng c ngha l gi thuyt ng, bi v tr s P ch ni ln tin cy ca phng php
kim nh thng k, ch khng phn nh kh d ca mt gi thuyt khoa hc. V
khng phn bit c hai khi nim ny, nn rt nhiu nh nghin cu din dch sai
ngha ca tr s P v kt qu nghin cu.

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 14
3.1 Cn phn bit P(+ve | K) v P(K | +ve)

Xin nhc li: P(+ve | K) l xc sut c kt qu xt nghim dng tnh nu c nhn
tht s mc bnh (hay t l nhng bnh nhn mc bnh ung th c kt qu dng tnh),
cn v P(K | +ve) l xc sut mt c nhn mc bnh nu kt qu xt nghim dng tnh
(tc l trong s nhng ngi c kt qu dng tnh, bao nhiu ngi tht s mc bnh).

Cn phi phn bit hai ch s trn!

Vn t ra l chng ta cn bit ch s no? Chng ta khng mun bit nu
bnh nhn mc bnh, xc sut m bnh nhn c kt qu dng tnh l bao nhiu, tc
P(+ve | K), tc l nhy. (Nu bnh nhn mc bnh th chng ta iu tr, ch khng
cn hi cu hi ngc v qu kh nh th!)

i vi bc s v bnh nhn, khi nhn c kt qu xt nghim [hy cho l]
dng tnh, ngi ta mun bit xc sut m c nhn mc bnh l bao nhiu. Tc l
chng ta mun bit P(K | +ve). Trong chn on y khoa, thut ng cho ch s ny l
positive predictive value (PPV), hay gi tr tin lng dng tnh.

3.2 c tnh P(K | +ve)

Gi tr tin lng dng tnh ty thuc vo ba thng s: nhy, c hiu ca
phng php xt nghim, v tn s mc bnh trong cng ng (cn gi l t l lu hnh
prevalence). Theo thng l khoa hc quc t, gi nhy l Se, c hiu l Sp, v t l
lu hnh l P. Vi ba thng s ny, chng ta c th c tnh gi tr tin lng dng
tnh:

( )
( ) ( )
|
1 1
P Se
P K ve
P Se P Sp

+ =
+
[1]

V d: N bnh nhn ngi M, 50 tui, i xt nghim ung th v v kt qu
dng tnh. Bnh nhn mun bit xc sut m b tht s mc bnh l bao nhiu? Y vn
cho bit nhy ca phng php X quang (mammography) l 90% (tc Se = 0,90), v
c hiu l 95% (hay Sp = 0,95). Y vn cng cho bit trong nhng ngi u tui
bnh nhn, c khong 1% (hay P = 0,01). Da vo cng thc trn, chng ta c th c
tr li cu hi ca bnh nhn:


( )
( ) ( )
0, 01 0, 90
|
0, 01 0, 9 1 0, 01 1 0, 95
P K ve

+ =
+
== 0,15

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 15
Ni cch khc, xc sut m bnh nhn tht s mc bnh nu kt qu xt nghim
dng tnh l 15%. Ni c th hn, c 100 ph n nh bnh nhn c kt qu xt nghim
dng tnh, khong 15 ngi tht s mc bnh ung th v. Tuy nhin, chng ta vn
khng bit v ph n nm trong s 15 bnh nhn hay khng!


3.3 c tnh P(H1 | S)

Tng t, trong nghin cu y hc, chng ta cng mun bit nu kt qu kim
nh c ngha thng k (S) th xc sut m gi thuyt chnh ng l bao nhiu. Ni
cch khc, chng ta mun bit P(H1 | S).

Cng nh trong chn on y khoa, P(H1 | S) ty thuc vo ba thng s: power
hay P(S | H1), sai st loi I, v xc sut m gi thuyt H1 ng l bao nhiu hay P(H1).
Gi sai st loi I l , chng ta c th c tnh P(H1 | S) nh sau:

( )
( )
( ) ( )
1
1|
1 1 1
P H power
P H S
P H power P H

=
( +

[2]

Trong cng thc trn, hai thng s u (power v sai st loi I) thng c
hoch nh trc khi nghin cu c thc hin. Thng thng, power dao ng trong
khong 0,80 n 0,90, v sai st loi I thng = 0,01 n 0,05. Nhng P(H1) c l l
thng s kh nht trong nghin cu, v trong nhiu trng hp chng ta khng bit xc
sut H1 l bao nhiu. Tuy nhin, ty trng hp c th, chng ta c th tip cn P(H1)
qua tn s ca mt s kin. Chng hn nh trong nghin cu v mi lin h gia mt
gien v bnh, trong s 30.000 gien, xc sut m mt gien c lin h n bnh c th l
1/30.000, hoc cao hn cht t nu c bng chng khoa hc lm c s.

V d: Mt nghin cu v mi lin h gia gien VDR v long xng, cc nh
nghin cu c tnh rng h cn 1000 i tng c power 90% v sai st loi I l 1%.
Kt qu phn tch thng k cho thy mi lin h c ngha thng k vi tr s P = 0,015.
Cu hi t ra l xc sut m gi thuyt v mi lin h gia VDR v long xng l bao
nhiu? Chng ta tm thi cho xc sut P(H1) = 1/30000 = 0,0000333. p dng cng
thc trn, chng ta c:

( )
[ ]
0, 0000333 0, 9
1|
0, 0000333 0, 9 1 0, 0000333 0, 05
P H S

=
+
= 0,0006

Ni cch khc, cho d kt qu c ngha thng k, nhng xc sut m VDR tht
s c lin quan n long xng ch 0,06% -- mt mi lin h cn qu nhiu bt nh.

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 16
Cng thc (1) v (2) va trnh by trn chnh l nh l Bayes (Bayesian theorem)
rt ni ting trong xc sut hc [13]. nh l Bayes pht biu rng c th c tnh xc
sut mt s kin sau khi c d liu quan st st hay o lng c. Ni mt cch thc
t hn, c th xem nh l Bayes l qui trnh cp nht ha kin thc. Trong v d v chn
on trn, trc khi xt nghim, chng ta bit rng xc sut m ngi ph n mc
bnh l 1% (t l lu hnh). Sau khi kt qu xt nghim dng tnh, xc sut ny tng ln
15% -- hay 15 ln. Tng t, trc khi lm nghin cu, chng ta c th ni rng xc sut
gien VDR lin h n long xng l 0,0000333, nhng sau khi c s liu dng tnh,
chng ta c th ni xc sut ca mi lin h ny ln 0,0006, tc tng gn 1800 ln, nhng
vn cn nhiu bt nh.


4. Yu t Bayes

Mt trong nhng kh khn trong vic c tnh P(H1 | S) theo nh l Bayes nh
va trnh by vn l xc nh thng s P(H1), hay cn gi l xc sut tin nh ca mt
gi thuyt (prior probability of a hypthesis). y cng chnh l im gy ra nhiu tranh
lun m mu sc trit hc trong sut 100 nm qua.

Mt cch khch quan hn nh gi hai gi thuyt l so snh trc tip kh nng
ca hai gi thuyt . Thay v c tnh trc tip xc sut mt gi thuyt, chng ta c th
c tnh xc sut d liu cho mt gi thuyt. Gi D (vit tt t data) l d liu, H0 l gi
thuyt v hiu, v H1 l gi thuyt chnh, chng ta nh ngha:

P(D | H0) l xc sut d liu quan st c nu gi thuyt H0 ng; v

P(D | H1) l xc sut d liu quan st c nu gi thuyt H0 ng.

Yu t Bayes (Bayes Factor BF) [14-15] c nh ngha nh l t s ca hai xc sut
trn:

( )
( )
| 1
| 0
P D H
BF
P D H
= [3]

Nu chng ta xem d liu D l bng chng, th Yu t Bayes chnh l mt o lng bng
chng nghing v gi thuyt no. Nhn qua cng thc trn chng ta c th thy:

Nu BF = 1, bng chng khng nghing v mt gi thuyt no c (hai gi thuyt
c xc sut nh nhau);

Nu BF > 1, bng chng nghing v (ym tr) gi thuyt H1 hn l H0;

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 17
Ngc li, nu BF < 1, bng chng nghing v (ym tr) gi thuyt H0 hn l
H1.

Theo mt qui c chung, cch din dch Yu t Bayes nh sau:

Yu t Bayes (BF) Bng chng nghing v H1 mc
BF = 3 n BF = 10 ng k (substantial evidence)
BF = 10 n BF = 30 thuyt phc (strong evidence)
BF = 30 n BF = 100 rt thuyt phc (very strong evidence)
BF > 100 gn nh xc nh

V d: Trong nn dch tiu chy vo cui nm 2007 mt s tnh pha Bc, mt
s quan chc y t cho rng mm tm l nguyn nhn, l ngun gc ca nn dch, v h
nghi rng mm tm hm cha vi khun gy bnh t (Vibrio cholerae). Vin v sinh dch
t trung ng xt nghim 75 mu mm tm c chn ngu nhin t H Ni, Ngh An,
v Thanh Ha. Kt qu xt nghim tt c u m tnh (khng c vi khun t). Chng ta
c th din gii bng chng ny nh th no?

Gi l xc sut mm tm cha vi khun t. Chng ta bit rng theo lut phn
phi nh phn (binomial distribution), nu xc sut nhim t l , v nu chng ta xt
nghim n mu, th xc sut c k mu b nhim l:

( ) ( ) | , 1
n k
k
n
P k n
k

| |
=
|
\


Gi H0 l gi thuyt mm tm khng hm cha vi khun t, do , = 0. Vi 75 mu
mm tm c xt nghim, chng ta c k = 0 (khng c kt qu dng tnh). Do , xc
sut k = 0 di gi thuyt H0 l:

( ) ( ) ( )
75 0
0
75
| 0 0 | 0, 75 0 1 0
0
P D H P
| |
= =
|
\
= 1

Nu H1 l gi thuyt mm tm c vi khun t, chng ta hy cho rng 20% mm tm
nhim khun, v do : = 0,20. Xc sut d liu (k = 0) di gi thuyt ny l:

( ) ( ) ( )( ) ( ) ( )
8 0 75 0 75
2 , 0
39 , 5 2 , 0 1 2 , 0 75 ; 2 , 0 | 0 1 |

= = = P H D P

Do , Yu t Bayes, theo nh ngha (3) l:

YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 18
( )
( )
( )
8
| 1
1
| 0
5.39
P D H
BF
P D H

= = = 18.546.031

Ni cch khc, bng chng (d liu t 75/75 m tnh) nghing v gi thuyt mm
tm khng nhim vi khun t n 18,5 triu ln!

Trn y l mt cch tnh tng rt n gin minh ho cho ngha ca Yu t
Bayes. Trong thc t, cc nghin cu vi cc phn tch phc tp, cch tnh Yu t Bayes
cng rt phc tp. Tuy nhin, chng ta c th c tnh gi tr ti thiu ca Yu t Bayes
c th c tnh bng mt cng thc rt n gin, ch l hm s ca tr s p, m Sellke v
ng nghip [16-17] pht trin nh sau:

BF
min
> 1 / (e p ln(p) ) [4]

Trong e = 2,71828. Chng hn nh mt nghin cu vi tro s p = 0,05, Yu
t Bayes ti thiu l: 1 / (-2,71828 x 0,05 x log(0,05)) = 2,45. Theo cch hiu thng
thng, khi p <0,05, cc nh nghin cu kt lun rng kt qu c ngha thng k
(significant), nhng vi cch tnh khch quan trn, chng ta thy bng chng vn cha
thuyt phc. Nhng khi tr s p rt thp nh v d trn vi p = 0,0009, th gi tr ti thiu
ca BF l 1/(-2,71828 x 0,0009 x log(0,0009)) = 58,3. Ni cch khc, bng chng c v
nghing v gi thuyt H1 nhiu hn l gi thuyt H0.

Qua nh l Bayes [xem ch thch 3], chng ta bit rng
( )
( ) ( )
( ) D P
H P H D P
D H P

=
|
| . Dng nh l ny v qua vi thao tc i s, chng ta c
th din t xc sut ti a ca P(H+ | s) nh l hm s ca BF nh sau:

( )
( )
( )
1
1 1
1| 1
1
P H
P H S
BF P H

( (

= + (

(



Do , theo v d trn, vi gi tr ti thiu BF l 58,3, v P(H1) = 0,5, chng ta c th c
tnh xc sut ti a ca P(H1 | S) l 0,983. Nu chng ta chp nhn xc sut >0,95 kt
lun, th qua cch tnh ny, chng ta c bng chng (p =0,0009) kt lun rng gi
thuyt H1 c xc sut ng ln n 98%.

Hy ly mt v d khc: mi y bo ch kh quan tm v mt nghin cu m
trong cc nh nghin cu pht hin rng t l b ung th v trong cc ph n dng
thuc aspirin (gim au) cao hn cc ph n khng dng aspirin khong 20% [6]. Kt
lun ny ch n thun da vo tr s p = 0,022, tc c ngha. Cc nh nghin cu
khng gii thch c hin tng ny, v pht hin cng nm ngoi d on sinh hc ca
YKHOA.NET - Nghin cu khoa hc Nguyn Vn Tun 19
h. Ni cch khc, y xc sut gi thuyt H1 rt thp, c th ch 0,01 (tc 1%). V
nu P(H1) = 0,01, v gi tr ti thiu BF l 1/[-2,71828 x 0,022 x log(0.022)] = 4,38, xc
sut ti a ca P(H1 | S) ch 0,042 hay 4,2%.

Cho d P(H1) = 0,1 i na, xc sut ti a ca P(H1 | S) cng ch 0,33. V xc
sut P(H1 | S) thp hn 0,95, chng ta c th pht biu rng gi thuyt v mi lin h
gia aspirin v ung th v cha c bng chng thuyt phc, hay bng chng hin c
khng nht qun vi gi thuyt . Ni cch khc, cc nh nghin cu c th i n
mt kt lun sai v pht hin ca h c th l mt pht hin dng tnh gi!

5. Vi nhn xt v kt lun

Tr s p l mt s c nh hng cc k ln n hot ng khoa hc. Nhiu tp
san v nh khoa hc xem mt nghin cu khoa hc vi tr s p cao hn 0,05 l mt kt
qu tiu cc (negative result) v bi bo c th b t chi cho cng b. Chnh v th
m i vi i a s nh khoa hc, con s P < 0,05 tr thnh mt ci giy thng
hnh cng b kt qu nghin cu. Nu kt qu vi P < 0,05, bi bo c c may xut
hin trn mt tp san no v tc gi c th s ni ting; nu kt qu P > 0,05, s phn
bi bo v cng trnh nghin cu c c may i vo lng qun!

Nhng cn phi nhn mnh mt ln na hiu ngha ca tr s P nh sau: Mc
ch ca tr s p l nhm tr li cu hi: nu gi thuyt v hiu H0 ng, th xc sut m
d liu chng ta quan st c l bao nhiu? Ni cch khc, chnh l phng php
chng minh o ngc. Do , din dch tr s P phi c iu kin. Tr s P khng cung
cp cho chng ta mt nh lng g ni n mt gi thuyt.

Trong sut mt th k qua khoa hc thc nghim da vo tr s p ca trng phi
thng k [c khi] gi l frequentist (trng phi tn s) suy lun v i n kt cc
lun khoa hc. Cch suy lun ny hin vn l cch lm vic chun trong khoa hc. Th
nhng ci logic ng sau tr s p c rt nhiu vn , k c s phn trc gic (counter-
intuitive) v rt kh hiu, c khi ... phi logic. Theo trng phi tn s, xc sut c nh
ngha ch qua th nghim (experiments) m trn l thuyt cc th nghim c th lp i
lp li nhiu ln n v tn, trong nhng iu kin ging nhau nhng c lp vi nhau.
Ni c lp c ngha l th nghim th hai khng c lin quan g n th nghim th
nht hay bt c th nghim no sau . V d nh mt ng xu c qung 1 ln, th
cng chnh l mt th nghim, v nu ng xu c qung lin tc 1 triu ln cng c
ngha l 1 triu th nghim, v cc th nghim ny c lp vi nhau. Theo cch hiu
ny, xc sut c ngha l s ln mt s kin xy ra trong v s th nghim , v tn s
ny c din t qua con s t l hay phn trm. Ni cch khc, xc sut l mt tn s
tng i (relative frequency).

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Ni cho cng, xc sut l mt cm nhn c nhn, l mc tin tng ca mt c
nhn v mt s kin hay hin tng no . Ni cch khc, xc sut phn nh kinh
nghim c nhn, hay kh nng ca c nhn tch ly v phn tch thng tin t cc
ngun ngoi ti. Do , cu pht biu xc sut aspirin gy ra ung th v l 0.33 phn
nh mc tin tng ca ngi pht biu i vi mi lin h gia aspirin v ung th v.
V l cm nhn c nhn, con s cng c cm nhn khc nhau gia cc c nhn: i
vi ng A, 0,33 c th l mc tin tng cn thp; nhng i vi ch B, 0.33 c th l
mt kh d cao. V l cm nhn c nhn, con s xc sut khng phi l mt ch s khch
quan nh cch hiu ca trng phi tn s. Theo trng phi tn s, xc sut n thng
minh hn nam l 0,98 c th c din dch nhiu cch khc nhau: n c th c ngha l
trong 100 cp nam n c chn mt cch ngu nhin, c 98 cp m trong ch s IQ
ca n cao hn nam; n cng c th c ngha l nu nghin cu c lp li 100 ln, mi
ln vi i tng khc nhau, c 98 nghin cu cho thy s trung bnh IQ ca phi n cao
hn phi nam. Tt nhin, trong thc t t ai nu khng mun ni l chng ai chu kh
lp li nghin cu 100 ln hay 1000 ln; do , cch din dch ca trng phi tn s rt
l phi thc t.

Trong suy lun khoa hc, c th ni khng ngoa rng ch c suy lun da vo
nh l Bayes l logic nht. Tuy tr s p = P(D | H0) v tr s P(H1 | D) hay P(H1 | S)u
l xc sut, nhng tr s p theo trng phi tn s cho chng ta bit nhiu v tnh chnh
xc ca nghim ton thng k, hn l v mc kh d ca mt gi thuyt nghin cu.
i vi nh nghin cu ch c P(H1 | S) l c ngha, cng nh i vi bnh nhn ch c
P(K | +ve) l c ngha. Mun c tnh mc kh d ca mt gi thuyt nghin cu,
chng ta cn phi ng dng nh l Bayes v cc phng php lin quan n nh l
Bayes. Qua bi vit mang tnh gii thiu ny, tc gi hi vng thuyt phc bn c, nht
l cc nh nghin cu thc nghim, nn tm hiu v tip cn cc phng php thng k
thuc trng phi Bayes, hin ang rt thnh hnh trong lnh vc y sinh hc, vt l hc, v
ngay c tin hc. Hi vng bn c s c dp ng gp vo s pht trin ca cc phng
php Bayes trong tng lai v lm cho suy lun khoa hc hon ho hn v logic hn.

Ch thch v ti liu tham kho:

[1] Lyles KW, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl
J Med 2007 Nov 1;357(18):1799-809.

[2] Wulff HR, Andersen B, Brandenhoff P, Guttler F. What do doctors know about statistics?
Statistics in Medicine 1987; 6:3-10.

[3] Karl Popper (28/07/1902- 17/09/1994), ngi o, ng c coi l mt trit gia khoa hc
hng u ca th k XX. Tc phm chnh u tin, Logik der Forschung (The Logic of Reseach),
xut bn nm 1934, c coi nh l mt tc phm kinh in ca php phn nghim, mt trng
phi ph bin ca ch ngha thc chng logic (logical positivism), ri tip cn n khoa hc c
gi l ch ngha phn nghim (falsificationism), m c s da trn php ph phn hn l xc
minh. T m ng c thnh ging Anh quc, m sau ny tr thnh qu hng th hai
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ca ng. T l thuyt phn nghim ca ng m sau ny ngi ta c th phn nh s khc bit
gia khoa hc vi ngu khoa hc. ng nhn c rt nhiu gii thng vinh d ca c Hip hi
Khoa hc Chnh tr M, Vin Hn lm Anh v.v.. ng c N hong Elisabeth II phong tc
hip s nm 1965, v Hun chng Danh d nm 1982. Ngoi tc phm ni ting nu trn ng
cng hin cho khoa hc th gii nhiu tc phm v gi v trit l khoa hc.

[4] bit trit l phn nghim trong nghin cu lm sng, c th c bi ca Senn SJ.
Falsificationism and clinical trials. Stat Med 1991 Nov;10(11):1679-92.

[6] Fisher RA. On the interpretation of
2
from contingency tables, and the calculation of P.
Journal of the Royal Statistical Society 1922; 85(1):87-94.

[6] Fisher RA. Statistical Methods for research workers. Oliver and Boyd, 1954.

[7] Neyman J, Pearson E. On the Problem of the Most Efficient Tests of Statistical Hypotheses.
Philosophical Transactions of the Royal Society of London. Series A, Containing Papers of a
Mathematical or Physical Character 1933; 231: 289-337.

[8] Xem thm chi tit v nhng tranh lun lin quan n kim nh ngha thng k v kim nh
gi thuyt trong sch The Significance Test Controversy, do DE Morrison v RE Henkel bin tp,
Nh xut bn Aldine, Chicago: 1970.

[9] Gigerenzer G, Swijtink Z, Porter T, Daston L, Beatty J, Kruger L. The Empire of Chace: How
Probability Changed Science and Everyday Life. Cambridge University Press, 1989.

[10] Barnard GA. Must clinical trials be large? The interpretation of P-values and the
combination of test results. Stat Med 1990;9(6):601-14.

[11] Barnard GA. On alleged gains in power from lower P-values. Stat Med 1989;8(12):1469-77.

[12] Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS; ACTS Study Group.
Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med
2006;354(17):1796-806.

[13] Thomas Bayes (1702 1761) l mt linh mc sng Anh vo th k 18. Ngoi cng vic
ging gio l, ng cn l nh ton hc c hng. Nm 1763 (tc sau khi ng qua i), mt ngi
ng nghip ca ng cng b mt cng thc xc sut m ngy nay c bit n l nh l Bayes
(Bayesian theorem) do ng vit lc cn sng nh v qu cn thn nn ng khng cho xut bn.
nh l ny c mt nh hng cc k to ln trong nghin cu khoa hc v chn on y khoa,
nhng cng l mt nh l gy ra nhiu tranh ci gay gt trong khoa hc sut 2 th k qua (m ti
s cp n trong mt dp khc). gii thch nh l ny ngn gn, c l chng ta cn phi
im qua vi s tht c bn v xc sut c iu kin (conditional probability).

tin theo di l gii, ti s dng k hiu H l gi thuyt v D l d kin nh cp trong phn
u ca bi vit. Nh chng ta bit, nu hai hin tng H v D c lp, th xc sut c iu kin
pht biu rng:

P(D H) = P(D|H) x P(H) [A1]
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Ni cch khc, P(D|H)= P(DH) / P(H), vi iu kin d nhin l P(H) khng phi 0. n
y bn c thy P(D|H)chnh l sai st loi I m ti cp. Hay ni c th hn
P(D|H)chnh l P(S|H0) sau khi nghin cu d kin c phn tch bng mt kim nh
thng k.

Nhng vn l chng ta mun c tnh P(H|D). Mt vi sp xp cng thc [A1] chng ta s
i n nh l Bayes:

P(H|D) = P(D|H) x P(H) / P(D) [A2]

ngha ca nh l Bayes trn y l mun c tnh xc sut mt gi thuyt H sau khi quan
st d kin D, th chng ta phi bit xc sut ca d kin hay P(D), v quan trng hn ht l xc
sut ca gi thuyt, tc P(H).

Mun tm hiu thm v l thuyt v ng dng thng k theo trng phi Bayes (Bayesian
Statistics) c th tham kho cc sch mang tnh nhp mn sau y: (1) sch v l thuyt: Peter M.
Lee, Bayesian Statistics, 2nd Edition, London: Arnold, 1997; (2) sch v ng dng: Donald A.
Berry, Statistics: A Bayesian Perspective, Belmont: Duxbury Press, 1996; (3) hay sch cho cc
nh vt l hc: Giulio DAgistini, Bayesian Reasoning in Data Analysis, World Scientific, 2003.

[14] Jeffreys H. The Theory of Probability (3e), Oxford (1961); trang 432.

[15] Goodman SN. Toward evidence-based medical statistics. 2: The Bayes factor. Ann Intern
Med 1999;130 (12): 1005-13.

[16] Sellke T, Bayarri MJ, Berger JO. Calibration of p-values for testing precise null hypothesis.
The American Statistician 2001.

[17] Berger JO, Sellke T. Testing a point null hypothesis: the irreconcilability of P-values and
evidence. Journal of the American Statistical Association 1987; 82:112-20.