1 Epidemiology Kept Simple Chapter 5: Introduction to Study Design

Intro to Epi Study Design Chapter 5 Intro to Epi Study Design 5.1 Introduction to Etiologic Research 5.2 Ethical Conduct of Studies in Human Subjects 5.3 Selected Elements of Study Design 5.4 Common Types of Epidemiologic Studies

Main types of epidemiologic studies Observational Studies Experimental Studies [Chapter 6] Aggregate-level unit of observation Person-level unit of observation Cross-Sectional [Chapter 5] Longitudinal Community trials Ecological [Chapter 4] Field trials Clinical trials Cohort [Chapter 7] Case-Control [Chapter 8] We aim to understand the concepts behind this study design taxonomy Before considering epi study design further, let us consider epidemiologic hypotheses

4 Epi Hypotheses 1.Studies must address clearly defined research hypotheses (“research questions”) 2.Hypotheses must based on sound causal mechanisms in specific terms that can be tested 3.Hypotheses are refinement as new information becomes available Hypotheses are like nets; only he who casts will catch. -- Novalis Skip to slide 10

5 Hypothesis Statement

6 Selected elements of an epi research question 1.Source population 2.Exposure variable (E) 3. Disease variable (D) 4.Extraneous “confounding” variables (C 1, C 2,…, C k ) 5.Dose-response 6.Time-response 7.Sample size

Variables “Yaz” example E → D C 1 ─┘ C 2 ─┘ C k ─┘ Example: Does the progestin in Yaz (DRSP) cause more venous thromboembolism (VTE) than 2 nd generation progestins? Research question in general terms: Does exposure E cause disease D after considering the contributions of “potential confounders” C 1, C 2, …, C k ? DRSP → VTE Age ────┘ Trauma──┘ Surgery──┘

8 Ethics: Studying Human Subjects The Belmont Report –Respect for individuals –Beneficence –Justice IRB oversight Data Safety Monitoring Board (DSMB) Informed consent Equipoise

9 Equipoise ≡ balanced doubt Cannot knowingly expose a participant to harm Cannot withhold known benefit to study subjects What’s left? (ANS: equipoise) Is equipoise the over-riding principles of trial ethics?

Scientific Ethics Ethics = the set of standardized rules for conducting yourself: like the tax code  people are looking for loopholes and shelters while still staying within the rules Scientific ethicsScientific ethics is beyond “regular” ethics; scientific ethics is “a bending over backwards to obtain intellectual honesty” –“I cannot give any scientist of any age any better advice than this: The intensity of the conviction that a hypothesis is true has no bearing on whether it is true or not.” (Peter Medewar) Peter Medewar

11 Advocacy vs. Scientific Ethics The term “advocacy” is used in the general sense as applied to public health, commercial, political, and other types of interests  pThe term “advocacy” is used in the general sense as applied to public health, commercial, political, and other types of interests  planned with the end result in mind.” Scientific ethicsScientific ethics: A bending over backwards to prove oneself wrong. “I cannot give any scientist of any age any better advice than this: The intensity of the conviction that a hypothesis is true has no bearing on whether it is true or not.” Sir Peter Medewar

12 Selected Study Design Elements Referent group Experimentation Unit of observation “Longitudinalness” Case-control vs. cohort

The Referent Group We can only judge the effects of an exposure relative to the baseline determined by a referent or “control” group “The question of course is not whether there is an association in the minds of any particular individuals. The question is whether the specific exposure contributed to the causal mechanism of the disease”

14 Experimentation Question. Does vitamin C (the exposure) prevent colds (the disease outcome)? AssignExperimental Study. Assign vitamin C supplementation to some subjects (E+) and gives others a placebo (E-). Compare cold rates in the groups. ClassifyObservational Study. Classify people into those who take vitamin C (E+) and those who don’t (E−). Compare cold rates in the groups. Did the protocol assign the exposure?

Experiment Randomized Experiment Observational cohort Randomized Experiment vs. Observational Cohort

16 Unit of Observation Question. Does cigarettes smoking (the exposure) cause lung cancer (the disease outcome)? individualsPerson-level data. Classify individuals as smokers or non-smokers. Assess & compare rates of LungCA in exposed and nonexposed groups. regions.Aggregate-level data. Classify level of smoking in various regions. Assess & compare rates of LungCA according to regional smoking rates. Are data available on individuals?

17 Longitudinal v X-sectional Question. Does exercise (the exposure) prevent diabetes (the disease outcome)? track individuals experience over timeLongitudinal measurement. Identify exercisers (E+) & non-exercisers (E−)  track individuals experience over time to assess and compare incidence rates of diabetes. currentCross-sectional measurement. Assess current exercise habits to assess and compare prevalences of diabetes. Can you track individual experience over time?

18 Case-Control vs. Cohort Hypothesis. Does cigarette smoking cause lung cancer? Cohort. Identify smokers (E+) and non-smokers (E-)  assess and compare lung cancer rates Case-control sample. Identify lung cancer cases (D+) and non- cases (D-)  assess and compare smoking histories (E+/E- ) Selection of subjects based on exposure (cohort) or disease (case-control) status?

odds of prior exposures

Illustrative Example 5.6: Toxic Shock and Continuous Tampon Use 44 cases and 44 friend controls 42 (95%) of the 44 cases used tampons continuously throughout menstruation 34 (77%) of 44 controls did similarly  cases more likely to use tampons continuously Eventually lead to the discovery that Rely brand tampons were too absorbent

(c) B. Gerstman 2007Chapter 921

Major types of epidemiologic studies Observational Studies Experimental Studies [Chapter 6] Aggregate-level unit of observation Person-level unit of observation Cross-Sectional [Chapter 5] Longitudinal Community trials Ecological [Chapter 4] Field trials Clinical trials Cohort [Chapter 7] Case-Control [Chapter 8]

23 Taxonomy I. Experimental studies (“trials”) – Ch 6 II. Observational studies A. Individual-level data 1. Longitudinal (a) Cohort studies - Ch 7 (b) Case-control studies – Ch 8 2. Cross-sectional – Ch 5 B. Aggregate-level data Ecological – Ch 4

Exercise 5.1 Instructions Clearly state the research question Identify the study exposure Identify the study outcome Determine the type of study according to our taxonomy

Exercise 5.1A Epidemiologists suspect that avian adeno-associated virus is caused by exposure to poultry. Serum samples from poultry workers and the general population are tested to determine the proportion of individuals positive for avian A–V antibody in each group. 1) experiment or observational 2) individual or aggregate unit of observation 3) longitudinal or X-sectional observation 4) cohort v case-control sample? Type of study = x-sectional observational study

Exercise 5.1B The behavioral pattern identified as Type A behavior is characterized by a hard-driving personality susceptible to anger and time urgency. This type of behavior is thought to be associated with increased risk for coronary heart disease. Type A behavior is ascertained in a group of men in a postcoronary disease rehabilitation program. Men not falling into the Type A category are classified as Type B. Type A and Type B men are then followed for 5 years to assess for the recurrence of acute coronary symptoms.. 1) observational 2) individual 3) longitudinal 4) cohort Type of study = observational cohort study

Exerise 5.1G One hundred incident cases of infectious hepatitis… 1) observational 2) individual- 3) longitudinal 4) case-control sample? Type of study = case-control!

Exerise 5.1H Questionnaires are mailed to every tenth person listed… 1) observational 2) individual 3) X-sectional observation 4) Type of study = x-sectional survey

Exerise 5.1I An investigator collects information on the size of manufacturing plants.. 1) observational 2) aggregate Type of study = ecological study!

Exerise 5.2 You have developed a hypothesis that automobile drivers that talk on their cell phones…. (A)How might you measure the exposure in a cohort study? Heavy talkers, Non-talkers (B)How might you identify cases in this [cohort] study (C)What additional factors…? (D)What difficulties might be encountered when measuring (E)How would we design a case-control study to test…