1. Types of Research Studies Architecture of Clinical Research
Professor Md. Akram Hossain
May 2009

2. Learning Objectives
Be familiar with the types of research study designs
Be aware of the advantages, disadvantages, and uses of the various research design types
Recognize a study design from published study abstracts used as a class exercise

3. Studies in Medical Literature
Two main categories:
Observational:
Studies in which subjects are observed
Experimental:
Studies in which the effect of an intervention is observed

4. Observational Studies
Case Series
Case-Control
Cross Sectional
Cohort

5. Observational Studies
Case Series
What are they?
Author describes some interesting or intriguing observations that occurred to a small number of patients
Characteristics:
The simplest design
Descriptive
Lead to hypotheses subsequently investigated by other types (Case-Control, Cross-Sectional or Cohort study)
Generally over short period of time
Generally no controls

6. Case Series & Case Reports

7. Observational Studies
Case-Control
Retrospective
Question answered: “What happened?”
Matching needed for controls
Might be difficult to differentiate from Case Series (Both are after the fact)
Ask if the goal was to describe a phenomenon, if description is the goal  Case Series

8. Case Control Studies

9. Case-control Studies: research in reverse
Example: association between smoking and lung cancer.
People with lung cancer are enrolled to form the case group, and people without lung cancer are identified as controls.
Researchers then look back in time to ascertain each person's exposure status (smoking history), (retrospective design). Investigators compare the frequency of smoking exposure in the case group with that in the control group, and calculate a measure of association.

10. Observational Studies
Cross Sectional
AKA Surveys, epidemiologic or prevalence studies
What are they?
Analyzes data collected on a group of subjects at one time
Question answered: “What is happening now?”
Short time

11. Cross Sectional (cont’ed)
Possible uses of Cross Sectional studies:
Diagnosing or staging a disease
Evaluating different methods of doing the same thing
e.g. Examining the relationship between histology slides and MRI findings of diseased carotid arteries
Establishing norms
e.g. Establishing normal lab values from normal subjects
Surveys
May use preexisting validated surveys
To learn what people think
Sometimes combined with interviews

12. Observational Studies
Cohort
Question answered: “what will happen?”
Prospective/forward
e.g. Framingham study of cardiovascular disease: Started in 1948, 6000 citizens participated, followed for 20 years (study in 1970 by Gordon and Kannel)
Possible uses:
Typical cohort study
Outcome assessment (patient outcomes: economic, functional, satisfaction, QOL, ..)
Historical Cohort studies/AKA Retrospective cohort: Relies on prospective records collected (If accurate) – still forward in time in the past

13. Cohort Studies

14. Cohort studies: marching towards outcomes
Lancet 2002; 359:
The defining characteristic of all cohort studies is that they track people forward in time from exposure to outcome. Data collection may be prospective or retrospective. Ex. Contraceptives and DVT.

15. Both Cohort and Case-Control studies are called “Longitudinal Studies”
Notion of time

16. Observational Studies
Case Series
Case-Control
Cohort
Cross Sectional
Longitudinal Studies

17. Experimental Studies AKA Clinical Trials (Involve humans)
Easier to identify (usually explicitly stated in the abstract)
Two main categories of clinical trials:
Controlled trials
Uncontrolled trials

18. Experimental Studies Controlled trials
Experimental drug or procedure compared with another, with a placebo, or with the standard procedure
Greater validity

19. Experimental Studies Controlled Trials
Trials with independent concurrent controls
Double or single blind
Best is randomized assignment
Same point in time
These include:
RCT:
The epitome of all research designs
Provides the strongest evidence of concluding causation
Best insurance that results are due to the intervention
Nonrandomized trials:
Assignment not randomized
Opened to biases
Trials with self controls
Subject to bias (Hawthorne effect)
Can do crossover study (with washout period in between)
Trials with external control
Uses the results of another investigator’s research as a comparison
Historical controls can also be used: for disease with no cures yet

20. Randomized Controlled Studies

21. The Double Blind Method

22. Experimental Studies Uncontrolled trials
Investigator’s experience with the new drug or procedure is described but not formally compared with another one
More likely to be used for interventions that are procedures rather than drug

23. Independent concurrent controls
Experimental Studies
Controlled trials
Uncontrolled trials
Independent concurrent controls
Self controls
External controls
RCT
Non-randomized

24. Systematic Reviews &Meta-analyses

25. Study Pyramid
Best
Worst

26. Classification of types of clinical research
Lancet 2002; 359: 57-61

27. Temporal direction of study designs
Lancet 2002; 359: 57-61

28. Advantages & Disadvantages

29. Clinical Trials Advantages: Disadvantages:
RCT is the gold standard or reference
Disadvantages:
Expensive
Long duration

30. Cohort Studies Advantages: Disadvantages:
Design of choice for studying cause of a disease, course, risk factors
Disadvantages:
Cannot be used to prove causation
Long studies can be costly
Vulnerable to patient attrition, migration

31. Case-Control Studies Advantages: Disadvantages: Quickest
Least expensive
Good for rare diseases and diseases that take long time
Good for investigation of a preliminary hypothesis
Time factor research
Disadvantages:
Large biases
Difficult to find matching controls

32. Cross Sectional Studies
Advantages:
Best for:
Determining status quo of a disease
Prevalence of disease
Evaluation of diagnostic procedures
Relatively quick and inexpensive
Disadvantages:
Provide only a snapshot in time

33. Case Series Advantages: Disadvantages: Easy to write
May be extremely useful to investigators looking for causes of the observation
Disadvantages:
Subject to many biases in patient selection
Should be viewed as hypothesis generating, not conclusive