1. Study Designs for Clinical and Epidemiological Research Carla J. Alvarado, MS, CIC University of Wisconsin-Madison (608) 263-2177 carla.alvarado@mail.admin.wisc.edu

2. An Overview of Study Designs u The purpose of most medical research is to find causes of disease and ways to treat or prevent them u Some studies are as simple as the astute observation of a new disease or problem - the case report u Others are complex and expensive like the clinical trial

3. Research steps to prepare for selecting an appropriate study design u Define the problem u State the research question(s) u Review the literature u Select a study type or design u Develop the protocol

4. Research Steps (continued) u Pilot test your study protocol u Collect data u Analyze data u Write the report and disseminate findings

5. Stating the Research Question u Clear, specific terms u “specific aims” of the trip u what u who u where u when

6. An Overview of Study Designs u Each study design has its own strengths and limits u Each study design type has associated problems that can distort your conclusions and lead you astray!

7. Experimental Studies u Distinguished by the fact members of the study population are assigned to either a treatment or control group u Treated and untreated groups are followed prospectively to see whether the two groups subsequently differ u Design most analogous to laboratory experiments

8. Experimental Studies u Not enough money to permit every interesting question to be answered u In the case of an adverse outcome, it is unethical to assign patients to the “control” group u Rare events require thousands of persons to be exposed u Even experiments are subject to bias

9. Randomized Clinical Trial u The best design to look at cause and effect u Subjects without the outcome are: u assigned to different exposures u receive different interventions u followed over time to determine occurrence of the outcome

10. Randomized Clinical Trial - 2 u Advantages u accurate information on exposure u accurate information on outcome u confounding less a problem u gives the strongest evidence of causality u Disadvantages u cost, time and complexity u no one wants to be control - people want new treatments u people (including medical staff) don’t want selection by chance u ethical issues

11. Observational Studies u Study in which the treatment or exposure of interest is not assigned, but occurs by choice or happenstance u Depend on people’s natural or voluntary exposures to factors not ordinarily randomly assigned u Always the possibility that the exposed and unexposed differ in important ways other than “exposure”

12. Observational Study: The Case Report u Described small number of persons with an unusual disease or change in disease possibly related to single cause u The first statement of clinical hypothesis u While case reports may lead to important findings, they cannot be a “finding” themselves because the observation may be due to chance

13. Observational Study: The Descriptive Study u Uses data that are routinely collected for various purposes to study the occurrence of disease and its possible causes among groups of groups u Most appropriate for preliminary exploratory studies u Inferences drawn from studying groups are not necessarily true for individuals

14. Observational Study: The Cross- Sectional Study u A cross-sectional (prevalence) study looks for an association between an outcome and possible causes by studying a group at one point in time u Can demonstrate an association between a factor and an outcome, but cannot say which came first u Can provide preliminary exploration u Relatively cheap and easy

15. Observational Study: The Cross- Sectional Study - 2 u Advantages u relatively inexpensive u relatively more simple u can represent a target population (generalizability) u good starting point for research u Disadvantages u cannot determine the cause (chicken v. egg) u recall bias

16. Observational Study: The Case Control Study u Begins with cases who have the disease of interest and a comparison group (controls) without the disease u Previous exposures of both groups are investigated u If previous exposure is more common among the cases, this is evidence that exposure caused the disease

17. Observational Study: The Case Control Study – 2 u Differs from other observational designs in that investigation begin with “ill” and works back to document possible causes of their illness u This approach is a refinement of the case report – adds group without the illness u Problems are by what criteria the comparison group is chosen

18. Observational Study: The Case Control Study – 3 u Advantages u relatively quick and inexpensive u requires fewer subjects u good for diseases with long latency periods u good for rare outcomes u can look for more than one exposure u Disadvantages u selection bias u “over matching” u “under matching” u recall bias

19. Observational Study: The Cohort Study u Starts with one group exposed to a factor of interest and another group unexposed u Groups are then observed at a later time to see if they develop differences that might be attributable to exposure u Most often prospective: however, can be retrospective in use of past data

20. Observational Study: The Cohort Study u Advantages u selection bias generally not a problem u recall bias not a problem u can look at more than one outcome u lends strength to causality because of temporal sequence u Disadvantages u long follow-up u may require many subjects u expensive u exposure may change over time

21. Potential problems within a study design u The “Confounder” u What looks like a casual relationship may be due to another factor not taken into consideration u Confounding factor is associated with bother hazard and the disease in a way the hazard and disease look related u The observed association between two conditions is actually secondary to the influence of a third factor

22. Potential problems within a study design-2 u The “Matchmaker” u Under-matching is the failure to select cases and controls sufficiently alike in important characteristics; can demonstrate a spurious association between a disease and a supposed cause u Over-matching is the error of selecting controls that excessively resemble cases; can fail to discover an association that is present and real

23. Potential problems within a study design-3 u The Cohort effect u Tendency for persons born in certain years to carry a relatively higher (or lower) risk of a given disease throughout their lives u Age distribution of the disease under study may be spuriously affected by differences in past experiences among various birth cohorts in the study population