EPI 5240: Introduction to Epidemiology An Overview of the Primary Study Designs September 28, 2009

1. EPI 5240:Introduction to EpidemiologyAn Overview of the Primary Study DesignsSeptember 28, 2009 Dr. N. Birkett, Department of Epidemiology & Community Medicine, University of Ottawa

2. Session Overview • Classification of epidemiological study designs • Hierarchy of evidence • Brief overview of key designs • Ecological study • Case-control • Cohort • Randomized controlled trial

3. Scenarios (1) • A pediatric respirologist over coffee that, over the past few years, she has noticed an increase in the number of young children (between age 5 and 12) she has been referred with a diagnosis of asthma. In most cases, the parents express serious concern that the asthma is being caused by exposure to environmental chemicals or immunizations.

4. Scenarios (2) • This gets you interested. A number of questions enter your mind: • Has there really been an increase in incidence? • What are the characteristics of children with asthma? • Do children exposed to second hand tobacco smoke have a higher incidence? What about children living near major roads? Does this cause asthma? • What happens to children with asthma? • How well do standard treatments do in treating children with asthma? Does treatment affect survival, quality of life or nothing?

5. Types (1) • Can group the previous scenarios into 3 broad groups: • Descriptive /hypothesis generating /observational (1&2) • Analytic /hypothesis testing /observational (3&4) • Analytic /hypothesis testing /experimental (5) • Warning! ANY attempt to classify studies is doomed to failure. • Some studies just don’t ‘fit’ • Some studies have multiple objectives and/or designs.

6. Types (2) • Descriptive • Attempt to ‘describe’ a situation. • There is no a-priori hypothesis or theory being tested. Rather, we just want to learn about how the condition is distributed. • Tends to use very simple statistics. • Analytic • Usually more focused on pre-specified theories or hypotheses • Uses more complex statistics (e.g. logistic regression)

7. Types (3) • Hypothesis generating • Early stage study designed to generate hypotheses or ideas to be tested in more focused studies. • Very unusual to have NO prior hypothesis or theory. Some people argue science is never down in isolation from prior biases/hypotheses. • Most studies will generate hypotheses even if this isn’t their main purpose • Hypothesis testing • A main purpose of the study is to test a specific theory or hypothesis. • Uses more complex designs and statistics • Karl Popper and falsification.

8. Types (4) • Observational • Studies people ‘as they lie’. Decision about whether to be exposed is made by subjects • Most common epidemiological study type. • Most potential for bias and error. • Experimental • Exposure is determined by the investigator. • Most well known type is a Randomized Controlled Trial (RCT). BUT, this is not the only type. • Unethical in many situations (e.g. does smoking cause esophageal cancer?) • Often viewed as the ‘gold standard’ of study designs

9. Scenarios (3) • Has there really been an increase in incidence? • Obtain data from CIHI or ICES on children discharged from hospital with a diagnosis of asthma. Compute incidence and look for trends. • Chart review of family practice centres. • Look at diagnostic criteria • Systematic review of clinical criteria for childhood asthma to look for temporal changes.

10. Scenarios (4) • What are the characteristics of children with asthma? • Chart review of tertiary care hospitals • Review of CIHI or ICES data • Recruit group of children with asthma and ask them and their parents a range of questions about their past exposures • Lack of comparison group • Collect data for various counties and see if those with high asthma incidence have higher levels of air pollution.

11. Scenarios (5) • Do children exposed to second hand tobacco smoke have a higher incidence? What about children living near major roads? Do this cause asthma? • Collect a group of children with non-smoking parents and a group with parents who smoke. Follow them to see children with smoking parents are more likely to be diagnosed with asthma • Collect a group of children with asthma and a group of children of the same age and sex who do not have asthma. Ask question to see if the former groups has more parents who smoke. • Similarly for living near ‘major roads’ (need defining)

12. Scenarios (6) • What happens to children with asthma? • Identify a group of children with asthma. Follow them up every year to find out what has happened to them • Death • Treatment • Quality of life • Biomarkers; lab tests • Some design questions: • Do you need to follow any children without asthma? • When in the course of the disease should you recruit subjects?

13. Scenarios (7) • How well do steroids do in treating children with asthma? Does steroid treatment affect survival, quality of life or nothing? • Identify a group of children with ACE, some of whom have had steroid treatment and some who haven’t. Follow them up every six months to find out what has happened to them and compare the groups. • Identify children with newly diagnosed asthma. Flip a coin to determine if each child will be given steroids or not. All children will also get ‘standard care’. Follow-up them up as in above study.

14. Hierarchy of Evidence (1) • Studies can be roughly ranked on the strength of evidence the provide. • Only an approximate guide: a very bad RCT can provide less evidence than a really good case series.

15. Types of Epidemiological Studies Weaker • Case Study • Case Series • Ecological (correlational) Stronger

16. Laboratory and anecdotal clinical evidence suggest that some common non-antineoplastic drugs may affect the course of cancer. The authors present two cases that appear to be consistent with such a possibility: that of a 63-year-old woman in whom a high-grade angiosarcoma of the forehead improved after discontinuation of lithium therapy and then progressed rapidly when treatment with carbamezepine was started and that of a 74-year-old woman with metastatic adenocarcinoma of the colon which regressed when self-treatment with a non-prescription decongestant preparation containing antihistamine was discontinued. The authors suggest ...... that consideration be given to discontinuing all nonessential medications for patients with cancer.

17. RR(1μg/m3) =1.08 RR(10 μg/m3) =2.31

18. Types of Epidemiological Studies Weaker • Case Study • Case Series • Ecological (correlational) • Cross-Sectional • Case-Control • Cohort (Historical) • Cohort (Prospective) Stronger

19. Hierarchy of Evidence (2) • Cross-sectional study. • Measures subjects at one point in time. Like a political poll. • Tells you the number (or proportion) of people who have a condition at a point in time (prevalence). • Useful for estimating Burden of Illness • Can look at associations of risk factors with illness but a weak design to look at causation or etiology. • An association might be due to prolonging life, not causing the disease.

20. Hierarchy of Evidence (3) • Cross-sectional study. • incidence-prevalence bias (Neyman bias). • Consider type 1 diabetes mellitus. • Around 1910, it was a fatal disease (< 1 year survival). You wouldn’t find many cases in a cross-sectional study. • After insulin developed, people now live 20+ years • Cross-sectional study would show that most people with type 1 diabetes were using insulin while very few people without type 1 diabetes used insulin. But, insulin doesn’t cause diabetes.

21. Hierarchy of Evidence (4) • Case-control study. • Select a group of people with the disease or outcome of interest (cases) • Select a group of people without the disease or outcome of interest (controls or referent group) • Ask each group about history of previous exposure. • Compare occurrence of exposure in the cases and controls.

23. Case-Control Study (1) Disease YESNO YESaba+b NOcdc+d a+cb+dN Exposure

24. Hierarchy of Evidence (5) • Cohort study. • Select a group of people with the exposure of interest • Select a group of people without the exposure of interest • OR simply select a group of people with a range of exposure experiences • Follow all subjects up to determine if they develop new cases of the outcome. • Compare the incidence of the outcome in each group.

26. Cohort Study (1) Disease YESNO YESaba+b NOcdc+d a+cb+dN Exposure

28. Types of Epidemiological Studies Weaker • Case Study • Case Series • Ecological (correlational) • Non-randomized Clinical Trial • Randomized Clinical Trial (RCT) • Cross-Sectional • Case-Control • Cohort (Historical) • Cohort (Prospective) Stronger

29. Hierarchy of Evidence (5) • Randomized Controlled Trial. • Key feature: decision about which subjects are ‘exposed’ is made by the investigator. • Other than that, an RCT is just a cohort study. • Methodological standards are more rigorous since you have more control over the study and the participants. • Non-RCT’s • Can be very powerful in some settings • Latin squares; BIBD’s

30. RCT Population R Control Group Treated Group

31. Summary • Epidemiological studies have different purposes depending on the ‘stage’ of understanding • Key designs are • Ecological • Cross-sectional • Case-control • Cohort • RCT • Some designs are ‘better’ than others