Post on 08-Jan-2016
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OBSERVERENDE UNDERSØGELSER
Kim OvervadInstitut for Epidemiologi og SocialmedicinAarhus Universitet Forår 2002
Epidemiologisk design
Observerende undersøgelser• beskrivende: Undersøgelsesenheden er populationer
• regional variation• migrationsundersøgelser• korrelationsundersøgelser• tidsrækker
• analytiske: Undersøgelsesenheden er individer• tværsnitsundersøgelser• follow-up undersøgelser• case-kontrol undersøgelser
Eksperimentelle undersøgelser
Korrelationsundersøgelser
Biologi
• rationale
• tid
Ikke nødvendigvis personsammenfald
• niveau fejlslutning
Confounding
• variation i andre risikoindikatorer
Populationserfaring
Eksponering Syge Raske I alt Obs. Tid
+ a b n+ t+
- c d n- t-
I alt a+c b+d N T
Sampling• tværsnitsundersøgelse
• N• follow-up undersøgelse
• eksponerede og ikke-eksponerede (n+ og n-)• case-kontrol undersøgelse
• oftest syge og raske (a + c og b + d)
Cross – Sectional Study, 1
A cross-sectional study was carried out among women attending a university health service to investigate the determinants of cervical human papillomavirus (HPV) infection. A sample of 467 women were asked to complete a self-administered questionaire on socio-demographic variables and sexual behaviour at the time of their visit to the clinic. The prevalence of HPV infection was thenexamined in relation to marital status and lifetime number of male sexual partners (Ley et al., 1991).
Cross – Sectional Study, 2
Lifetime no. of
sexual partners
No. of
women
% positive
for HPV
(prevalence
proportion)
Prevalence proportion
ratio (95% CI)
1 90 21.1 1.0
2-3 101 32.7 1.5 (0.9-2.4)
4-5 93 54.8 2.6 (1.7-4.0)
6-9 66 56.1 2.7 (1.7-4.3)
10+ 102 68.6 3.3 (2.1-4.9)
Cross – Sectional Study, 3
Lifetime no of
sexual partners
HPV-
negative
HPV-
positive
No of
women
1 71 19 90
10+ 32 70 102
The prevalence proportion ratio for each exposure level was calculated by forming 2 x 2 tables as illustrated below for women with 10+ partners
Prevalence proportion among women with 10+ partners = 70/102 = 68.6%Prevalence proportion among women with one partner = 19/90 = 21.1%Prevalence proportion ratio = 68.6% / 21.1% = 3.3
Follow-up Study, 1
The Nurses’ Health Study is a cohort study of 121,700 US Female registered nurses aged 30-55 years when the cohort was established in mid-1976. A total of 1,799 newly diagnosed breast cancer cases were identified during the first 10 years of follow-up from mid-1976 to mid-1986. Analyses were then conducted to investigate the relationship between oral contra-ceptive use and risk of breast cancer. (Romieu et al., 1989).
Follow-up Study, 2
Oral contraceptive use Cases Person-years
at risk
Incidence rate per
100,000 pyrs
Ever (current or past use)
204 94,029 217
Never 240 128,528 187
Total 444 222.557 199
The incidence rates of breast cancer among nurses aged 45-49 years at the time of their entry into the cohort was examined in relation to use of oral contraceptives
Data from Romieu et al. (1989)
Rate ratio = 217 per 100,000 pyrs/187 per 100,000 pyrs = 1.1695% confidence for the rate ratio = 0.96 to 1.40Rate difference = 217 per 100,000 pyrs – 187 per 100,000 pyrs = 30 per 100,000 pyrs95% confidence interval for the rate difference = -8 to 68 per 100,000 pyrs
Fordele ved observerende follow-up undersøgelser
Fordele• direkte identifikation af studiebasen• indflydelse på eksponeringsfordelingen• kvalitetskontrol af data• eksponeringsoplysninger før sygdom• flere sygdomsudfald• mulighed for beregning af flere associationsmål
Ulemper ved observerende follow-up undersøgelser
Ulemper• ressourcer
• tid• penge
• enkelt eksponeringer• påvirkning af den diagnostiske proces eller
sygdomsregistreringen• etik
Oplysninger om eksponering
Hypoteser
Muligheder
• specifik (tid og sted)
• gennemsnit
• max/min
• kumuleret
Associationsmål
Eksponering Antal pers. Syge Obs. Tid
+ n+ a t+
- n- c t-
Follow-up undersøgelse, komplet follow-up
Relativt associationsmål• relativ risiko RR = a/n+ / c/n-
Absolut associationsmål• risiko differens RD = a/n+ – c/n-
Associationsmål
Eksponering Antal pers. Syge Obs. Tid
+ n+ a t+
- n- c t-
Follow-up undersøgelse, inkomplet follow-up
Relativt associationsmål• incidens rate ratio IRR = a/t+ / c/t-
Absolut associationsmål• incidensrate differens IRD = a/t+ – c/t-
Valg af associationsmål i follow-up undersøgelsen
Sygdomshyppigheden blandt ikke-eksponerede, et relativt og
et absolut associationsmål supplerer hinanden.
Follow-up undersøgelse
Eksponering Syge Raske I alt Obs.tid
+ a b n+ t+
- c d n- t-
Ved sjældne sygdomme er n+ og n- samt b og d meget større end a og c
Case-Control Study, 1
A population-based case-control study was carried out in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductivebehaviour, use of oral contraceptives, screening practices, smoking, and possible interactions between them. The study included 436 incident cases of histologically confirmed invasive squamous-cell carcinoma of the cervix and 387 control of similar age randomly selected from the general Population that generated the cases (Muñoz et al., 1992a).
Case-Control Study, 2
Number of
sexual partners
Cervical cancer cases
Controls Odds ratio (95% confidence interval)
0-1 265 305 1.0
2-5 125 74 1.94 (1.39-2.70)
6+ 46 8 6.62 (3.07-14.27)
Risk of developing cervical cancer in relation to the lifetime number of sexual partners.
Case-Control Study, 3
Number of
sexual partners
Cervical cancer cases
Control
0-1 (unexposed) 265 305
2-5 (exposed) 125 74
The odds ratios for each category of exposure were calculated in the following way:
Odds ratio = (125/265) / (74 x 305) = 1.94
Fordele ved case-kontrol undersøgelser
Fordele
• ressourcer
• tid
• penge
• flere eksponeringer
• hypotese genererende
• etik
Ulemper ved case-kontrol undersøgelser
Ulemper
• afgrænsning af studiebasen
• kvalitetskontrol af data
• eksponering
• effekt
• enkelt sygdomme
• ikke økonomisk ved studiet af sjældne eksponeringer
• associationsmål
Studiebasen
Studiebasen er den populationserfaring, vi ønsker at beskrive
på baggrund af undersøgelsen
Studiebasen er de personer, for hvem det gælder, at de ville
blive cases, givet de udviklede den sygdom, der studeres
Eksponering
Eksponeringssandsynlighed
Muligheder for at øge eksponeringssandsynligheden
• restriktion
• geografi
• køn
• alder
• andre specielle studiebaser
Associationsmål
Eksponering Syge Raske I alt Obs. Tid
+ a b n+ t+
- c d n- t-
Stikprøve af raske• case – non-case design
Associationsmål• OR = a/c / b/d• OR ~ RR
• sygdommen sjælden• RR tæt ved 1,0
Case-kontrol undersøgelse, komplet follow-up
Associationsmål
Eksponering Syge Raske I alt Obs.tid
+ a b n+ t+
- c d n- t-
Case-kontrol undersøgelse, komplet follow-up
Stikprøve af studiebase – personer i alt• case-base design• kumulativ incidens proportions sampling
Associationsmål• ”OR” ~ RR• uafhængig af sygdomshyppighed• uafhængig af størrelsen af RR
Associationsmål
Eksponering Syge Raske I alt Obs.tid
+ a b n+ t+
- c d n- t-
Case-kontrol undersøgelse, komplet follow-up
Estimerings- og vurderingsproblemer• cases i referencegruppen• statistiske metoder
Referencegruppen kan bruges i flere undersøgelser med forskellige endpoints
Associationsmål
Eksponering Syge Raske I alt Obs. Tid
+ a b n+ t+
- c d n- t-
Stikprøve af studiebasen – observationstid• case-base design• incidence density sampling• hver gang en case opstår samples reference personer fra den aktuelle studiebase
Case-kontrol undersøgelseInkomplet follow-up (censureringer)
AssociationsmålCase-kontrol undersøgelse
Inkomplet follow-up (censureringer)
Eksponering Syge Raske I alt Obs. Tid
+ a b n+ t+
- c d n- t-
Associationsmål• ”OR” ~ IRR
• uafhængig af sygdomshyppighed og størrelse af IRR
Estimerings- og vurderingsproblemer• cases i referencegruppen• statistiske metoder
Referencegruppen er specifik for den pågældende undersøgelse
Case-kontrol undersøgelse i follow-up undersøgelse
Ikke økonomisk at gennemføre en follow-up undersøgelse,
men heller ikke mulig at indhente relevante eksponerings-
oplysninger på det tidspunkt, hvor cases og referencepersoner
kan identificeres.
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