東南大學(xué)流行病學(xué)課件

1、case- control studyHui JinDepartment of Epidemiology and Health StatisticsSchool of Public Health, Southeast University2OverviewDesign of case-control studies Basic concept OR=RR? Exclusive (traditional) Inclusive (case-cohort) Concurrent (density) Case-to-case Case-crossoverWhy case-control study?

2、In a cohort study, you need a large number of the subjects to obtain a sufficient number of case, especially if you are interested in a rare disease. Gastric cancer incidence in Japanese male: 128.5 / 100,000 person year A case-control study is more efficient in terms of study operation, time, and c

3、ost. Case-control study - Sequence of determining exposure and outcome status Step1: Determine and select cases of your research interest Step2: Selection of appropriate controls Step3: Determine exposure status in both cases and controlsCase ascertainment What is the definition of the case? Cancer

4、(clinically? Pathologically?) Virus carriers (Asymptomatic patients) You need to screen the antibody Including deceased cases? You have to describe the following points, the definition when, where & how to selectCase definition Conceptual definition Obesity defined as body fat percentage 33% Ope

5、rational definition Body Mass Index 30Case definition: Issues Case definition should avoid misclassification For example: Sinha et al (2008) Anemia was defined as Hemoglobin kept in both groups OR estimates relative risk 48Cohort studyCases exposed End of studyExposed population (E)Unexposed populat

6、ion (U)Cases unexposed Still at risk Still at risk TimeRodrigues L et al. Int J Epidemiol. 1990;19:205-13.CasesSample of source populationStill at riskConcurrent design: density case control 49Concurrent design: density case control Controls selected from those still at risk when a case occurs Contr

7、ol can later become a case Not vice versa - cases no longer at risk Controls who later become cases kept in both groups Controls represent person years at risk experience among exposed and unexposed Matched analysis on time of selection OR estimates the rate ratio50How to select controls to estimate

8、 the respective measure of associationMeasureDesignFormulationAlternativeformulationControls to be sampled fromRisk ratioInclusiveCe/NeCu/NuCe/CuNe/NuRate ratio ConcurrentCe/pyareCu/pyaruCe/Cupyare/pyaruOdds ratio ExclusiveCe/(Ne- Ce)Cu/(Nu- Cu)Ce/Cu(Ne- Ce) /(Nu- Cu)Rodrigues L et al. Int J Epidemi

9、ol. 1990;19:205-13.Total study population regardless of past or future disease statusPeople currently at riskPeople disease-free throughout study period51 Rare diseases: all give similar results Non-recurrent disease with high incidence- Case cohort design (inclusive): OR relative Risk Recurrent com

10、mon disease - Density case control design (concurrent): OR relative Rate Probability or effect of exposure changes along time - Density case control design: OR relative Rate No need to quantify - traditional designWhat design and when?52Relationship between OR and RR, according to the primary attack

11、 rate (AR)Acknowledgements: Olivier le Polain, EPIET Cohort 15HPA London Epidemiology Unit, UK53Cases detected by surveillance systems Non-random selection process: Host factors (eg. asymptomatic infections) Different health care seeking behaviour Incomplete lab investigation Incomplete reporting Di

12、fferential recall Between reported and not reported cases Between cases and controls54Case-to-case approach Same disease, different subtypes/clones: Serotypes Phage types Antibiotic resistance patterns Controls = cases with non epidemic subtypes from same source population same susceptibility (under

13、lying diseases) included as cases if they had the outbreak strain readily available Reduces selection AND recall bias Food-exposure collected before status is known55Case-crossover design Same person taken as its own control - No between-persons confounding Matched design: Compare exposure in a risk

14、 period to one or more control periods Only pairs of discordant periods used in the analysis Acute diseases Exposure must vary over time short induction and transient effect sensitive to recall bias Reference period “Wash out”period Currentperiod ExposureStudyCasesMatched pairs1Discordant 0, 12Disco

15、rdant 1, 03Concordant 1, 14Concordant 0,0 Case-crossover design57Folic acid antagonists (FAA) in pregnancy and congenital cardiovascular defects (CCD) Case-crossover approach Case: Woman who had a child with CCD (N=3870) Exposure: FAA during 2nd & 3rd month of pregnancy Control: Woman who had a

16、child without CCD (N=8387)OR=1.0 (0.5-2.0)OR= 0.3 (0.2-0.6)Case-time control OR = 1/0.3 = 2.9 (1.2-7.2)-2 -1 1 2 3 4 5 6 7 8 9Cases:-2 -1 1 2 3 4 5 6 7 8 9Controls:ControlperiodRiskperiodDeliveryHernandez-Diaz S. Am J Epidemiol 2003;158:385-39158Conclusions If you do not need that OR estimates correctly the RR - “traditional design” Otherwise, if you need OR RR- identify the best design for each situation If it is