Types of Research StudiesArchitecture of Clinical Research

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

Learning Objectives

Two main categories:1. Observational:

Studies in which subjects are observed2. Experimental:

Studies in which the effect of an intervention is observed

Studies in Medical Literature

Case Series Case-Control Cross Sectional Cohort

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

Observational Studies

Case Series & Case Reports

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

Observational Studies

Case Control Studies

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.

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

Observational Studies

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

Cross Sectional (cont’ed)

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, ..) Historical Cohort studies/AKA Retrospective cohort:

Relies on prospective records collected (If accurate) – still forward in time in the past

Observational Studies

Cohort Studies

Both Cohort and Case-Control studies are called

“Longitudinal Studies”

Notion of time

Observational Studies

Case Series Case-Control Cross SectionalCohort

Longitudinal Studies

AKA Clinical Trials (Involve humans) Easier to identify (usually explicitly stated

in the abstract) Two main categories of clinical trials:

1. Controlled trials2. Uncontrolled trials

Experimental Studies

Controlled trials– Experimental drug or procedure

compared with another, with a placebo, or with the standard procedure

– Greater validity

Experimental Studies

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

Experimental StudiesControlled Trials

The Hawthorne effect (also referred to as the observer effect) is a type of reactivity in which individuals improve an aspect of their behavior in response to their awareness of being observed.

washout period: A period in a clinical study during which subjects receive no treatment for the indication under study and the effects of a previous treatment are eliminated.

Randomized Controlled Studies

The Double Blind Method

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

Experimental Studies

Experimental Studies

Controlled trials Uncontrolled trials

Self controls Independent concurrent controls

External controls

RCT Non-randomized

Systematic Reviews &Meta-analyses

Study Pyramid

Best

Worst

Temporal direction of study designs

Lancet 2002; 359: 57-61

Advantages & Disadvantages

Advantages:◦ RCT is the gold standard or reference

Disadvantages: ◦ Expensive◦ Long duration

Clinical Trials

Advantages:◦ 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

Cohort Studies

Advantages: ◦ 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

Case-Control Studies

Advantages: ◦ Best for:

Determining status of a disease Prevalence of disease Evaluation of diagnostic procedures

◦ Relatively quick and inexpensive Disadvantages:

◦ Provide only a snapshot in time

Cross Sectional Studies

Advantages: ◦ 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

Case Series

Thank you