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1 Depatment of Public Health Case-contol design Bief summay: e e - Case-contol design Katine Standbeg-Lasen Depatment of Public Health, Section of Social Medicine Fo at få øg, bug mind Compaison of cases vs. contols with egad to thei level of exposue Compae the odds of exposue in cases vs. contols Cases Contols Enh n Sted The selection of contols must not depend upon exposue Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side The definitions of population Pincipal idea Taget population: The goup fom which a study population is selected and about which infeences ae desied Study population: The goup selected investigation, and actually contibute with inmative data Souce population (study base): The goup of pesons (o peson time) fom which the outcome of inteest is obseved. - Pimay base: pecisely defined and identified population - Seconday base: Not possible to identify the study population explicitly it is identified secondaily to identification of cases Rothman KJ. Moden epidemioly. 2008; Last JM. A dictionay of epidemioly Fo at få øg, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Think of the souce population as a hypothetical cohot Collect inmation: - Cases (a andom sample o all) - Contols (a andom sample) That is what makes, this design is moe: - Efficient - Well-suited ae outcomes Souce population Diseased individuals Contols Time

2 In basic In basic The outset is individuals with disease (cases) and a sample fom the souce population (contols) Compae the odds of exposue in cases vs. contols Is often called a etospective design as it stats afte the onset of disease and looks back. Howeve, can be pospective so called it case-contol design We use the Contols as a measue of the exposue fequency in the souce population Time Fo at få Cases øg, bug mind Contols Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Requie, that the sampli of contols NEEDS to be independent of exposue Contols need to be sampled fom the same souce population as cases, i.e. ae at i (at least in theoy) of becomi a case THUS, all case-contol studies can be viewed as nested within a hypothetical cohot Note: the nested case-contol design involves a specific selection of contol Time Cases Contols The cohot design Case-contol design Souce population Study population Fo at få øg Souce population Contols Study population Cases, bug mind Souce- =study population Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side

3 Altenative pesentation of the cohot design Measui associations in cohot design In a cohot we know the numbe of pesons at baseline Ill people Fo at få øg Exposue Disease Non-disease Numbe at baseline Time at i + a b N + (a+b) T + Healthy people (at i), bug mind - c d N - (c+d) T - Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Ri: an + and cn - Relative i: atio of the is, RR= (an + )(cn - ) Incidence ate (IR): at + and ct - Incidence ate atio: atio of the IR s, IRR=(aT + )(ct - ) Case-contol design Measui association in case-contol design Ill people Samples all ill people (o a specified faction) diseased Non-diseased Contols Fo at få øg Sample a specified numbe of contols pe case + a b - c d This implies: Not possible to estimate: The numbe o popotion of ill people (i) in exposed vs. unexposed Possible to estimate: The numbe o odds of exposed in cases vs. contols, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Odds exp cases = a c Odds exp contols = b d Odds atio (OR): the atio of odds of exposue in cases vs. contols OR exp = a c b d

4 Measui association in case-contol design Specific challees diseased Non-diseased + a b - c d Odds exp cases = a c Odds exp contols = b d Odds atio (OR): the atio of odds of exposue in cases vs. contols Fo at få øg, bug mind Defi and identifyi the souce population easy in counties with population wide egisties Identification and selection of contols, so that they ae epesentative of the exposue fequency in the souce population Select contols independent of exposue OR exp = a c b = a d a = b b c c d d = OR dis Enh n Sted Often etospective collection of inmation on exposue Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Smoki and lu cance Case-noncase o case base study Fo at få øg Contols ae selected amo those who stay fee of disease Cases cannot be selected as contols Association measue: OR if used to estimate the RR, then emembe the ae disease assumption, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side

5 Enh navn Nested case-contol (incidence density sampli) Fo at få øg, bug mind Contols ae selected amo the population at i evey time a case occus, i.e. a peson get ill. Does not imply complete follow-up Cases can be included as contols if they become cases at a late point in time Association measue: OR is a diect estimate of IRR Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Enh navn Selection of contols Enh navn Fo at få øg, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side

6 Enh navn Enh navn Fo at få øg, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Enh navn Case-cohot design Contols ae selected fom the baseline cohot Requies a clealy defined souce population (cohot) with complete follow up Cases can be included in the contol goup Association measue: OR is a diect estimate of i atio (RR) Fo at få øg, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side

7 Enh navn Enh navn Fo at få øg, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Enh navn Sub-types of case-contol design Fo at få øg, bug mind Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Case-non case Nested case-contol Case-cohot Contols ae selected amo those who stay fee of disease Cases cannot be selected as contols OR if used as estimate of RR then ae disease assumption Contols ae selected amo the population at i evey time a case occus Cases can be included as contols Requies a clealy defined souce population OR diect estimate of IRR Contols ae selected as a andom sample of the baseline cohot Cases can be included as contols Requies a clealy defined souce population with complete follow up OR diect estimate of i atio

8 Steths and weaknesses What design is used? STRENGTHS WEAKNESSES Snak med sidemanden i 2 min: Rae disease ando lo latency time Faste and cheape With a pope selection of contols diect estimate of i atio o IRR Fo at få Selection of contols can be challei not always possible to define øg the souce population, bug mind Often etospective collection of exposue data possibility of ecall bias En guppe ee va inteesseet i om bly i blodet kan give hjeneade. En kohote ae pesone fik i 1990 taget en blodpøve blev fulgt til med I alt blev 68 diagnosticeet med hjeneade i løbet af studiet. Foene undesøgte i 2011 blodpøvene fa de 68 pesone med hjeneade 312 ae pesone fa kohoten tilstedevæelse af bly. Foene konkludee at de ikke va en sammenhæ mellem bly i blodet senee hjeneade Examine a lot of diffeent suspected i factos No diect i estimate, but OR as estimates of i estimates Often challei to elucidate tempoality Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Ja, det e et case-kontolstudie di ene ha taget udgaspunkt i udfald ikke eksponei så selvom studiet e etaget inden en kohote! What design is used? How to intepet the OR? Snak med sidemanden i 2 min: En guppe ee va inteesseet i om bly i blodet kan give hjeneade. En kohote ae pesone fik i 1990 taget en blodpøve blev fulgt til med I alt blev 68 diagnosticeet med hjeneade i løbet af studiet. Foene undesøgte i 2011 blodpøvene fa de 68 pesone med hjeneade 312 ae pesone fa kohoten tilstedevæelse af bly. Foene konkludee at de ikke va en sammenhæ mellem bly i blodet senee hjeneade Fo at få øg, bug mind Ja, det e et case-kontolstudie di ene ha taget udgaspunkt i udfald ikke eksponei så selvom studiet e etaget inden en kohote! Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side

9 The MOBAND cohot e The MOBAND poject Fo at få øg 210,399 mothe-child dyads, n=96,835 fom DNBC and n=113,564 fom Moba 436 cases of ceebal palsy (CP), n=191 fom DNBC and n=235 fom Moba e - An epidemiolic study of ceebal palsy in the Nowegian and Danish bith cohots, bug mind Outcome is based on the National CP egisties, and additional identification of the Nowegian cases Self-epots on life style and othe exposues collected dui pegnancy and infancy in the DNBC and Moba Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side Data fom the National egisties, e.g. the Medical Bith Registy, and IVF-egisty DNBC ( ) and MoBa ( ) Compaison of the cohots Recuitment Week st inteview Week 16 FFQ Week 24 2 nd inteview Week 31 Bith 3 nd inteview 6 months Fo at få øg, bug mind Recuitment Week 17 1 st questionnaie. Week 17 FFQ Week 22 2 nd questionnaie Week 30 Bith 3 nd questionnaie 6 months Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side

10 e e - Matenal thyoid disode and i of ceebal palsy Results

11 Guidelines publicei e e - Assignment: Design a case-contol study within MOBAND that addess: If unegulated thyoid disode in pegnancy is associated with inceased i of unilateal spastic ceebal palsy Fo at få øg, bug mind The STROBE statement: Von Elm E et al. The Stethe the Repoti of Obsevational Studies in Epidemioly (STROBE) Statement - Guidelines Repoti Obsevational Studies. Epidemioly 2007;18: Enh n Sted Klik i menuli vælg Indsæ Sidehoved Side. Indføj Sted dato i feltet dato Enh n i Side