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

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

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

Observational Studies 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

Case Series & Case Reports

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

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.

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

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

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

Cohort Studies

Cohort studies: marching towards outcomes Lancet 2002; 359: 341-45 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.

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

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

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

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

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

Randomized Controlled Studies

The Double Blind Method

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

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

Systematic Reviews &Meta-analyses

Study Pyramid Best Worst

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

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

Advantages & Disadvantages

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

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

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

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

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