6. Overview of Epidemiologic Study Designs

1. 6. Overview of Epidemiologic Study Designs 2012. 04. 03. 역학 및 임상시험학4학기 이고은

2. 목차

3. LEARNING OBJECTIVES • Distinguish between experimental and observational studies. • Describe the key characteristics of experimental , cohort, case-control , cross-sectional, and ecologic studies regarding subject selection, data collection, and analysis. • Identify the design of a particular study. • Discuss the factors that determine when a particular design is indicated.

4. Introduction Several types of study designs • Experimental study • Observational study • Cohort study • Case-control study • Cross-sectional study • Ecological study

5. Introduction • Tab 6-1 • the goal of all studies • to determine the relationship between an exposure and a disease with validity and precision using a minimum of resources • Validity : lack of bias and confounding • Bias • Confounding • Precision : lack of random error • false association between exposure and disease by chance

6. 1. oVERview of experimental studies

7. Experimental study • Definition • investigate the role of some agent in the prevention or treatment of a disease. Trial • active manipulation • Classification • by objective • preventive or prophylactic trial • therapeutic or clinical trial

8. Experimental study • Fig 6-1 • Study population (=experimental population) • criteria reflect the purpose of the trial • adequate number for a true difference

9. Experimental study • Informed consent • the process of gaining agreement • contents • the nature and objectives of the study, the tasks required of the participants • obtaining the participant’s oral or written consent • Assignment • Randomization • Less prone to bias • Producing groups with very similar characteristics • ex) coin flipping, random number table, computer • Treatment administration • using placebo

10. Experimental study • Maintenance and assessment of Compliance • Noncompliance ⇒ smaller difference between groups ⇒ diluting the real impact of a treatment • Run-in period • 목적: to ascertain which potential participants are able to comply with the study regimen • run-in period 이후에 compliance가 좋은 대상자들만 시험에 등록된다 • Ascertaining the outcome • Outcome • 질병 예방이 목적일 때 : incidence • 질병의새로운 치료방법을 연구할 때 : disease recurrence, symptom improvement, length of survival, side effect • Length of follow-up : 연구중인 특정 결과에 따라 다름 • dropout, lost f/u에 따라 follow-up이 영향을 받을 수 있다

11. Experimental study • Analysis • Intent-to-treat (= treatment assignment analysis) • classic analytic approach • 치료를 받았거나 끝났는가에 상관없이 모두를 분석 • give information on the effectiveness of a treatment under everyday practice condition • Efficacy analysis • determines the treatment effects under ideal condition (full treatment exactly as directed)

12. 2. oVERview ofcohort studies

13. Cohort study • Cohort • Definition : a group of people with a common characteristic or experience. follow-up, incidence, longitudinal study • healthy subject incidence of symptom, disease, death • 연구대상의 일반적인 특징은 exposure level이 같다 • Fig 6-2

14. Cohort study • Terms • Characteristics of population • Fixed cohort • formed on the basis of irrevocable event • ex) undergoing a medical procedure • Closed cohort • a fixed cohort with no losses to follow up • Open population • exposures that can change over time (예: cigarette smoking) • f/u loss 가 있을 수 있다 • Timing • Prospective cohort study • past or current exposure future outcome • Waiting for outcome • Retrospective cohort study • Exposure and outcome already occurred study begins • Ambidirectional cohort study

15. Cohort study • Selection of the exposed population • Special cohort • For studying health effects of rare exposure • Uncommon work place chemicals • Unusual diets • Uncommon lifestyle • Selected from occupational group or religious group • General cohort • typically assembled by common exposures ex) cigarette smoking / alcohol consumption • Selected from professional groups or well-defined geographic area • Selection of the comparison population • Internal comparison group • Unexposed members of the same cohort • First choice • General comparison • When it is not possible to find a comparable internal comparison group • a comparison cohort • Members of another cohort. • the least option because often exposed to other potentially harmful substances

16. Cohort study • Sources of information • medical and employment records, interviews, direct physical exam, lab test, biological specimens, environmental monitoring • Health care records • Advantage: low expense, high level of accuracy and detail • Disadvantage: information (key characteristic) is often missing • Employment records • Used to identify individuals for studies of occupational exposure • Usually lack details on exposures and key information • All resources used for one group must be used for the other (∵biased results)

17. Cohort study • Approaches to follow-up • 잘.... • Analysis • the primary objective of the analysis of cohort study data : occurrence of symptoms, disease, death in the exposed group occurrence of symptoms, disease, death in the unexposed group • Occurrence measurement • cumulative incidence or incidence rate • Relationship between the exposure and outcome • Absolute or relative difference between risks or rates

18. 3. oVERview ofcase-control studies

19. Case-control study • Subjects are selected on the basis of whether they have or do not have the disease • cases : those who have the disease • controls : those who do not the disease • Fig 6-3

20. Case-control study • Selection of cases • Formulation of disease or case definition • Case identification and enrollment • Typical sources for identifying cases • Hospital or clinical patient rosters, death certificate, special surveys, cancer or birth defects registers • Should they be incident or prevalent? • 질병의 원인에 관심있는 연구자들은 incidence case를 선호한다 • 질병의 이환기간에 영향을 주는 factor 보다는 질병을 일으키는 factor에 더 관심이 있기때문 • Prevalent case외에 선택이 없는 연구를 해야 하는 경우도 있다 • ex) insidious disease whose exact onset is difficult to pinpoint • 해석에 주의해야 함 : Impossible to determine if the exposure is related to the inception of the disease, its duration, or a combination

21. Case-control study • Selection of controls • Controls • from the same base population as the cases • “would criterion” • Crucial to the validity • From the same population • A member of the control group who gets the disease under study would end up as a case in the study • Controls must be sampled independently of exposure status • Exposed and unexposed controls should have the same probability of selection • Sources for identifying controls 1. Individuals from the general population 2. Individuals attending a hospital or clinic 3. Friends or relatives identified by the cases 4. Individuals who have died

22. Case-control study • Population controls • typically selected when cases are identified from a well-defined population ex) residents of a geographic area • Advantage • from the same population as the cases • Disadvantage • Time-consuming and expensive to identify • Less interest in participating than cases • Less accurate recall (because generally healthy)

23. Case-control study 2. Hospital controls • Which disease or events are suitable for inclusion? • illness in the control group should be unrelated to the exposure • control’s illness should have the same referral pattern to the health care facility as the case’s illness • Advantage • Easy to identify, good participation rate, less expensive than population controls, comparable characteristics to the cases • Recall of prior exposures will be similar to the cases’ recall, because they are also ill. • Disadvantage • Difficulty in determining appropriate illness for inclusion

24. Case-control study 3. Decreased controls • Some or all of the cases are deceased by the time data collection begins • Same geographic area / same period • Comparable data collection procedure • ex) interview vs. interview • dead control • 죽은 사람들은 술, 담배, 마약을했을 가능성이 더 크다 4. Friend, spouse,relatives • Likely to share the cases’ socioeconomic status, race, age, educational level, genetic characteristic • Bias • If the study hypothesis involves a shared activity among the cases and controls

25. Case-control study • Methods for sampling controls • survivor sampling • Predominant • Select controls from the “non-Cases” or “survivors” at the end of the case diagnosis and accrual period • case-base or case-cohort sampling • Select controls from the population at risk at the beginning of the case diagnosis and accrual period • risk set sampling • Controls are selected from population at risk as the cases are diagnosed • Sources of exposure information • interview, self-administered questionnaires, preexisting medical, pharmacy, registry, employment, insurance, birth, death, environmental records • Consider availability, accuracy, logistics, cost of data collection • Accuracy! • Because : Retrospective exposure

26. Case-control study • Analysis : odds • Functions as rate of risk • Probability that an event will occur divided by the probability that it will not occur • = • odds ratio:

27. Case-control study • Case-Crossover study • a variant of the case-control study • Developed for only a brief time following the exposure • Cases serve as their own controls • hazard period와 control period의 exposure frequency 를 비교 • Advantage • Elimination of confounding by characteristics – gender, race • Elimination of selection bias • Variability is reduced ☞ traditional case-control study보다 더 적은 수로 연구가 가능함

28. 4. When Is It Desirable to Use a Particular Study Design? Experimental studyvs. observational study

29. When Is It Desirable to Use a Particular Study Design?-Experimental • Experimental study • To learn about a prevent or treatment for a disease • No need data with a high degree of validity that is simply not possible in an observational study (bias and confounding) • When small difference between groups • Usually < 20% difference

30. When Is It Desirable to Use a Particular Study Design?-observational • To study the effects of a wider range of exposures • Limitation • Inability to have complete control over disturbing influences or extraneous factors • cohort or case-control? • cohort : provide a large number of possible health effects  preferable when little is known about the health consequences of an exposure • cohort : efficient for investigating a rare exposure • frequency of less than 20%

31. When Is It Desirable to Use a Particular Study Design?-observational • cohort or case-control? • case-control : provide information on a large number of possible risk factors • preferable when little is known about the etiology of a disease • Less time, less money than cohort • For studying rare disease because fewer subjects are needed, and for studying disease with long induction and latent periods • When exposure data are difficult or expensive to obtain • Relatively smaller sample size • When population under study is dynamic • Disadvantage • Retrospective data collection • Greater chance of bias • Difficult to establish the correct temporal relationship between the exposure and disease

32. When Is It Desirable to Use a Particular Study Design?-observational • retro- or prospective cohort study? • Retrospective cohort study • To study historical exposure • studying disease with long induction and latent period • Limitation : rely on existing records • Minimal information • Difficult to establish the correct temporal relationship between exposure and disease • Prospective cohort study • Less vulnerable to bias than retro- (outcomes not occurred when the cohort is assembled) • easier to establish a clear temporal relationship between exposure and outcome

33. When Is It Desirable to Use a Particular Study Design?-observational • Fig 6-4

34. 5. Other types of studies

35. Cross-Sectional study vs. Ecological study Cross-Sectional study Ecological study • Examine association at a single point in time. • Measure exposure prevalence in relation to disease prevalence. • Examine rates of disease in relation to a population-level factor. • Population –level factor s include summaries of individual population members, environmental measures, and global measures. • Study groups are usually identified by place, time, or a combination of the two. characteristic characteristic • Tab 6-2 Limitation Advantage • Cannot infer temporal sequence between exposure and disease if exposure is a changeable characteristic. • May include preponderance of prevalent cases of long duration and healthy worker survivor • Generalizability and low cost Limitation Advantage • Ecological fallacy • Lack of information on important variables • low cost , wide range of exposure levels, and the ability to examine contextual effects on health

36. Cross-Sectional study • Definition • Examine the relationship between diseases (or other health-related characteristics) and other variables of interest • As they exist in a defined population at one particular time • Population selection • Without regard to exposure or disease status • ‘snapshot’, prevalence • If the dates of the exposures are ascertained • Possible to examine disease prevalence in relation to past exposures • For public health planning • For etiologic research • Common in occupational settings using data from pre-employment physical examinations and company health insurance plans • ex) low back pain among crane operator, straddle-carrier drivers, office workers

37. Cross-Sectional study • Limitation • Sequence?? between exposure and disease • People who die soon after diagnosis or who recover quickly • Less likely to be identified as diseased • Bias in occupational setting: Healthy worker survivor effect • Not include former workers • ‘remain’ tend to be healthier • Advantage • General population sample •  results highly generalizable • Need relatively short period of time(low cost) • Temporal inference problem can be avoided • If an inalterable characteristic(ex>genetic trait..) is focus • If exposure measure reflects present and past exposure • ex) x-ray fluorescence(XRF) measurement reflect cumulative exp.

38. 6. Ecologic studies

39. Ecological study • 2 key features • Population unit of analysis • Analysis unit : population or groups of people • An exposure status that is the property of the population • Identifying groups by place, time or combination • ex) place : air pollution and mortality rate • ex) time : HIV seroprevalence change over time among injecting drug users in cities with and without needle-exchange program

40. Ecological study • A special type of time-trend ecologic study • Separate the effects of three time-related variables: age, calendar time, year of birth • ex>Homicide mortality data from US from 1930s through 1990s • double • most of the increase : 1960 – 1974 • peak age : 20 to 39 years • men born around 1965 1985 to 1994 • alcohol, drug abuse, lethal weapons

41. Ecological study • Ecological and individual level components • chlorinated drinking water and birth defect(Norway) • group level data : exposure • individual level data : birth defect, confounding variables • population : children born in 1990s • 4 group : 0%, 0.1~ 49.9%, 59 ~ 99.9%. 100% • Overall 15% increase, 99% increased risk of urinary tract defects among women • Ecological fallacy or ecological bias • because of lack of individual level information • An association observed between variables on an aggregate level does not necessarily represent the association that exists at the individual level • woman(chlorinate water) ≠ woman(defect baby) • Inability to defects subtle or complicated relationship • ex>HIV seroprevalence: simultaneous other program

42. Ecological study • Advantage • done quickly and inexpensively (preexisting data) • achieve wider range of exposure levels • can be used to understand how context affects the health of persons and groups through selection, distribution, inter action, adaption, and other responses • studies of the transmission of infectious disease

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