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o lng nh hng:
Odds ratio, relative risk, risk ratio, hazard ratio
Nguyn Vn Tun
Trong bi Lm sng thng k 14, ti gii thch s lin h v khc bit gia
odds ratio (OR) v relative risk (RR), v nhng kh khn trong vic din gii OR. Gn
y c mt s bn hi ti v risk ratio v hazard ratio (HR) l g, v cch s dng cng
nh din gii cc ch s ny nh th no. Trong bi ny, ti s gii thch ngn gn cc
thut ng ny. Ti s khng dch sang ting Vit, v c cc bn c bit thut ng
nguyn thy ting Anh khi ra ngoi c dp hi nhp cng cc ng nghip quc t.
Nhng trc khi vo , ti mun k cho cc bn mt cu chuyn trong lch s y
khoa c lin quan n nguy c v xc sut. Christiaan Barnard l nh gii phu u tin
ghp tim (heart transplantation) trn th gii. Trong hi k ca mnh, ng thut li mt
cu chuyn v bnh nhn thay tim u tin trn th gii ca Barnard: l Louis
Washkansky. Khi c a vo phng gii phu, Washkansky ang say m c sch
trn ging nh khng g n mt s kin lch s y khoa sp xy ra. Barnard vo
phng gii phu, t gii thiu vi Washkansky, v gii thch tng tn rng ng s ct b
tri tim ca Washkansky v thay vo l mt tri tim mi lnh mnh hn. Barnard ni
thm: ng s c c may bnh phc (there is a chance that you can get back to normal life
again). Washkansky khng hi ci c may l bao nhiu, khng hi ng c th sng
bao lu na, m ch ni ti sn sng v quay li tip tc c sch! Barnard cm thy
rt lo u v bi ri, bi v Washkansky r rng khng thc c rng y l mt s
kin quan trng trong cuc i ca chnh ng m cn l mt s kin lch s trong y hc.
Nhng b v ca Washkansky hi: C may m bc s ni l bao nhiu? Barnard tr
li: 80 phn trm. Mi tm ngy sau cuc gii phu, Washkansky qua i. y,
con s 80% c hiu nh th no? C phi trong 100 ngi c phu thut th c 80
ngi sng st? Hay n phn nh mt tin tng, mt cm nhn c nhn ca bc s
Barnard? Phn di y s bn n ngha ca con s nguy c ny.
Cch th nht l dng con s phn trm: T l bnh ung th trong cng
ng l 2 phn trm (ly 20 chia cho 1000, ri ly kt qu nhn cho 100).
Odds v xc sut
Tt c din gii trn ch ni mt im: nguy c l xc sut, nhng xc sut c
th thiu theo trng phi ch quan hay trng phi tn s.
Xc sut khc vi odds. Odds l mt khi nim c th trong vn ha nh bc,
v ch c ngi Anh mi c thut ng odds, khng c ngn ng no trn th gii c ch
odds!
Nu trong s 100 bnh nhn c 10 ngi mc bnh trong mt thi gian theo di,
th nguy c mc bnh (k hiu p) l:
p = 10 / 100 = 0.10
hay 10%. Nhng odds c nh ngha l:
odds =
p
1 p
0.10
= 0.11
0.90
nh ngha OR, RR v HR
Cc ch s OR, RR v HR u o lng mc tng quan (magnitude of
association) gia mt yu t nguy c (risk factor) v nguy c mc bnh (risk of disease).
Nhng ngha tht ca chng c khi khc nhau. hiu r cc nh ngha ny, chng ta
s xem qua kt qu ca ba nghin cu sau y (ti s ch trng n RR v OR, v HR gn
nh l RR v s c gii thch trong mt phn sau):
Nghin cu 1: zoledronic acid v gy xng. Trong mt nghin cu gn y
v nh hng ca zoledronic acid, mt loi thuc chng long xng v nga gy xng
trong gia nh bisphosphonates, cc nh nghin cu tuyn chn 7736 ph n sau mn
kinh, tui t 65 n 89 (Black DM, et al. N Engl J Med 2007 May 3;356(18):1809-22).
H ngu nhin chia cc i tng nghin cu thnh 2 nhm: nhm 1 gm 3875 bnh
nhn c iu tr vi zoledronate, v nhm 2 gm 3861 bnh nhn trong nhm i
chng khng c tim zoledronate m ch ung calcium v vitamin D (cn gi l nhm
chng). Sau 3 nm theo di, c 92 ngi (t l 2.4%) trong nhm zoledronate gy xng,
v 310 ngi (hay 8.0%) trong nhm chng b gy xng t sng (vertebral fracture):
Bng 1. Tm lc kt qu nghin cu theo tng nhm i
tng sau 3 nm nghin cu v hiu qu ca zoledronic
acid.
Nhm
Zoledronate
Nhm chng
(Placebo)
3783
3551
92
310
3875
3861
Khng gy xng
Gy xng t sng
Tng s
Sng
123
200
II + III
416
300
Tng s
809
500
Ngun: http://lib.stat.cmu.edu/S/Harrell/data/descriptions/titanic3info.txt
Nghin cu 3: ung th phi v ht thuc l. Mt cng trnh nghin cu bnh
chng mang tnh lch s, v y l cng trnh ln u tin cho thy ngi ht thuc l c
nguy c mc bnh ung th phi. Nghin cu do Richard Doll v Bradford Hill thc hin.
H chn 649 ngi mc bnh ung th phi, v 649 ngi khng mc bnh (nhm
chng). sau , h tm hiu tin s ht thuc l. Kt qu ca cng trnh lch s ny c
th tm lc nh sau (R Doll and B Hill. BMJ 1950; ii:739-748):
Bng 3. Tn s ht thuc l trong nhm ung th phi v
khng ung th phi.
Ht thuc l
Ung th phi
Nhm chng
647
622
27
649
649
Khng ht thuc l
Tng s
Nghin cu 1 l nghin cu can thip trong m hnh randomized controlled trial (tc lm
sng i chng ngu nhin), nhng nghin cu 2 v 3 l nhng nghin cu quan st (tc
khng can thip). C th xem nghin cu 2 l mt nghin cu ct ngang (cross-sectional
study hay mt survey), v nghin cu 3 l nghin cu bnh chng.
Trong nghin cu 1, chng ta c th c tnh nguy c gy xng cho nhm iu tr (p1)
v nhm chng (p2) nh sau:
p1 =
92
= 0.024
3875
p2 =
310
= 0.080
3861
p1 0.024
=
= 0.295
p2 0.080
[1]
Ni cch khc, nguy c gy xng trong nhm bnh nhn iu tr bng zoledronic acid
gim ~71% so vi nhm chng.
Chng trnh hun luyn y khoa YKHOA.NET Training Nguyn Vn Tun
0.024
= 0.0243
1 0.024
O2 =
0.080
= 0.0872
1 0.080
O1 0.0243
=
= 0.279
O2 0.0872
[2]
123
= 0.381
123 + 200
P2 =
416
= 0.581
416 + 300
Do , RR l:
RR =
P1 0.381
=
= 0.655
P2 0.581
[3]
O1 =
123
= 0.615
200
416
= 1.387
300
Do , odds ratio t vong ca nhm hnh khch hng I so vi nhm hng II v III l:
OR =
O1 0.615
=
= 0.443
O2 1.387
[4]
Con s RR = 0.655 trn cho chng ta bit hnh khch hng I c nguy c t vong
trong tu Titanic thp hn hnh khch hng II v III khong 35% (ly 1 tr cho 0.655).
Nhng OR l 0.443, v nu c ngi can m din gii rng nguy c t vong ca
nhm hnh khch hng I thp hn nhm hng II v III l 56% th s rt sai. Sai l v vi
OR chng ta khng c th ni v nguy c hay risk, do n v ca OR l odds.
Ti sao trong nghin cu 1, RR v OR rt gn nhau, nhng trong nghin cu 2
RR v OR qu khc nhau? Nhn k cng thc tnh RR v OR, chng ta d dng thy mt
mi lin h hu c (nu bn no thch i s c th lm mt chng minh), v mi lin
h ny cho chng ta thy nu t l (nguy c) bnh thp (nh di p < 0.1) hay rt thp
(p < 0.01) th OR rt gn vi RR, nhng khi nguy c bnh cao (nh trn p > 0.2) th
OR lc no cng cao hn RR. Ni cch khc, OR lc no cng cao hn RR v mc
khc bit cng ln khi nguy c bnh cng cao (nh nghin cu 2, khi P trn 0.35).
Bng sau y trnh by 10 nghin cu (tng tng) m tt c u c RR bng 3,
nhng OR khc nhau. Nh c th thy qua bng ny, khi nguy c mc bnh cng cao th
OR cng cao hn RR.
Nguy c mc bnh
Odds of disease
Nhm 1
(p1)
0.001
Nhm 2
(p2)
0.003
Nhm 1
(O1)
0.002
Nhm 2
(O2)
0.003
0.01
0.03
0.01
0.02
0.06
0.05
0.10
So snh gia
RR v OR
RR
OR
3.01
0.03
3.06
0.02
0.06
3.13
0.15
0.05
0.18
3.35
0.30
0.11
0.43
3.86
0.15
0.45
0.18
0.82
4.64
0.20
0.60
0.25
1.50
6.00
0.25
0.75
0.33
3.00
9.00
0.30
0.90
0.43
9.00
21.0
10
0.33
0.99
0.49
99.0
2101.0
647
= 323.5
622
622
= 23.04
22
T , OR c c tnh:
OR =
O1 323.5
=
= 14.04
O2 23.04
cng c khi c xem l risk ratio (RR). C th xem incidence l tng ng vi khi
nim tc (velocity) bn vt l, v hazard l gia tc (acceleration) ca vt l.
hiu hazard ratio, chng ta th xem qua mt nghin cu dn s dch t hc m
trong cc nh nghin cu c tnh t l t vong ca nhng ngi trong tui 50-54,
55-59, 60-64 v 65-69 nh sau:
Bng 5. T l t vong tnh trn 100,000 dn s M 1990
Nguyn nhn t
vong
Ung th phi
Tim mch
50-54
55-59
60-64
65-69
91.1
276.1
176.0
473.6
289.9
766.6
399.1
1197.2
Ch trong cch tnh trn, chng ta phi nhn t l t vong cho 5 v trong mi nhm tui,
khong cch l 5 (nh 50 n 54). Mu s 100,000 l v t l trong bng trn c tnh
trn 100,000 dn s.
T , hazard ratio c nh ngha l t s ca hai nguy c tch ly:
HR =
P1 0.013266
=
= 0.36
P2 0.037679
Ni cch khc, nguy c t vong v ung th phi thp hn nguy c t vong v bnh tim
khong 64%.
Tm lc
kt thc bi ny, Bng 6 sau y tm lc mi lin h gia OR, RR v HR.
Ti mun nhc li mt s im chnh nh sau:
Khi nim nguy c l xc sut, khc vi khi nim odds khng phi l xc sut
m ch l mt t s. Do , v din gii, OR khng th din gii bng ngn ng nguy c,
nhng trong vi trng hp th OR cng c th xem l RR.
Trong dch t hc, chng ta mun c tnh relative risk (RR), cn c khi gi l
risk ratio. Nhng v trong nghin cu bnh chng, chng ta khng th c tnh RR, nn
phi c tnh OR. Do , OR chnh l mt c s (estimate) ca RR.
Nhng v OR rt d tnh, nn OR c th tnh cho bt c m hnh nghin cu
no (nh nghin cu bnh chng, ct ngang, hay nghin cu xui theo thi gian -prospective study). Nhng vi cc nghin cu m tn s bnh kh cao (trn 10%) th OR
lc no cng c tnh RR cao hn thc t (over-estimation). Chnh v th m ngy nay,
nhng ai hiu vn khng s dng OR hay hi qui logistic cho cc nghin cu nh th.
Tuy nhin, tnh prevalence ratio hay risk ratio trong cc nghin cu nh th i hi
phi bit s dng chng trnh R phn tch thch hp.
RR (relative risk hay risk ratio) ch c th c tnh cho nghin cu xui theo thi
gian hay ct ngang, ch khng th tnh t nghin cu bnh chng. HR ch c th c
tnh cho cc nghin cu xui theo thi gian vi iu kin chng ta bit chnh xc thi
im hay thi gian m bin c lm sng xy ra.
V mt thng k, OR c c tnh qua m hnh hi qui logistic; RR c tnh qua
m hnh hi qui Poisson hay hi qui nh phn; v HR th c tnh ch qua m hnh hi qui
Cox (Coxs proportional hazard model). Ti s bn qua cch phn tch v din gii cc
m hnh nh phn trong mt bi sau, nhng phn ph ch di y gii thch s qua v
m hnh Poisson.
Bng 6. Phn bit mt s ch s o lng nh hng, thut ng v phng php
phn tch
Ch s
Ngun gc
Tn gi khc
Odds ratio
Odds ratio
(Cornfield,
1951)
Relative risk
Cross-product
ratio
Relative risk
Risk ratio
Lut phn
phi
Nh phn
(binomial
distribution)
Poisson hay
Phng php
phn tch
Hi qui logistic
(Cox, 1958)
Poisson
10
(Cornfield,
1951)
Hazard ratio
Intensity of
mortality ratio
(Gompertz
1825)
Nh phn
Force of
mortality
Exponential,
Poisson
regression
(Cochran,
1940; Kutner
v Beauchamp
1973)
Coxs
proportional
hazards (Cox
1972)
Ph ch:
Mt dng nghin cu khc cng c th s dng risk ratio qua v d sau y. S
liu sau y l s trng hp mc bnh ung th da ph n thuc thnh ph song sinh
Minneapolis St Paul (M):
tui
15-24
25-34
35-44
45-54
55-64
65-74
75-84
85+
S trng
hp ung
th da
1
16
30
71
102
130
133
40
Dn s
T l pht sinh
trn 1000 dn s
172,675
146,207
121,374
111,353
83,004
55,932
29,007
7,538
0.0058
0.1094
0.2472
0.6376
1.2289
2.3243
4.5851
5.3064
11
(ct s 4) nh l mt t l pht
Ni
sinh bnh. By gi, tin cho vic tnh ton, chng ta hon chuyn t s ny sang n
v logart:
log i
Ni
= log( i ) log( N i )
[1]
M hnh ny pht biu rng log ca t l pht sinh, tc l log i , l mt hm s ca
Ni
tui (v chng ta k hiu tui bng x). Ni cch khc, m hnh ny pht biu rng:
log i
Ni
= + xi
[2]
[3]
M hnh [3] chnh l m hnh hi qui Poisson (Poisson Regression). Cch din
t m hnh theo cng thc [3] cho php chng ta xy dng mt hm s kh d
(likelihood function) c tnh cc thng s v . Trong m hnh trn, log( N i )
c gi l offset, tc l im nhn.
Chng ta c th s dng R c tnh cc thng s trong m hnh [3] nh sau:
age = c(19.5,29.5,39.5,49.5,59.5,69.5,79.5, 89.4)
cases = c(1, 16, 30, 71, 102, 130, 133, 40)
pop = c(172675, 123065, 96216, 92051, 72159, 54722, 32185, 8328)
dataset = data.frame(age, cases, pop)
fit = glm(cases ~ age + offset(log(pop)), family=poisson,data=dataset)
summary(fit)
Kt qu ca phn tch l:
Deviance Residuals:
Min
1Q
Median
-4.87198 -1.67519 -0.07185
3Q
1.20816
Max
1.99291
Coefficients:
Estimate Std. Error z value Pr(>|z|)
12
(Intercept) -10.551604
0.168780 -62.52
<2e-16 ***
age
0.063629
0.002475
25.71
<2e-16 ***
--Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
(Dispersion parameter for poisson family taken to be 1)
Null deviance: 845.789
Residual deviance: 44.288
AIC: 91.688
on 7
on 6
degrees of freedom
degrees of freedom
i
Ni
= e 10.552 +0.064 x
i
Ni
i
Ni
13
14