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Types of Research StudiesArchitecture of Clinical Research

Rani Gereige, M.D., MPH, FAAPAssociate Professor of Pediatrics

Associate Director, Residency ProgramUniversity of South Florida

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:1. Observational:

• Studies in which subjects are observed

2. 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 Cross SectionalCohort

Longitudinal Studies

Experimental Studies

• AKA Clinical Trials (Involve humans)

• Easier to identify (usually explicitly stated in the abstract)

• Two main categories of clinical trials:1. Controlled trials

2. Uncontrolled trials

Experimental Studies

Controlled trials

– Experimental drug or procedure compared with another, with a placebo, or with the standard procedure

– Greater validity

Experimental StudiesControlled 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

Experimental Studies

Controlled trials Uncontrolled trials

Self controls Independent concurrent 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:– RCT is the gold standard or reference

• Disadvantages: – Expensive– Long duration

Cohort Studies

• 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

Case-Control 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

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: – 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

Class Exercises

What Type of Research Design?

Exercise #1

Cryptosporidiosis is an enteric illness that is frequently waterborne. Khalakdina and colleagues (2003) could find no published studies of the risk factors for cryptosporidiosis in immunocompetent adults. Patients with cryptosporidiosis were recruited from a surveillance system, and age-matched controls were recruited by random-digit dialing. Subjects in both groups were interviewed by telephone to obtain information about previous exposures

What is the Study Design?

Drossman DA, Li Z, Leserman J, Toomey TC, Hu YJ. Health status by gastrointestinal diagnosis and abuse history. Gastroenterology

1996;110:999-1007.

• BACKGROUND & AIMS: Standardized assessment of health status by diagnosis (functional vs. organic) and the relative influence of abuse history on health status have not been studied previously. The aim of this study was to estimate the health status and abuse history for gastrointestinal diagnoses among patients seen in a tertiary-care gastroenterology clinic and to evaluate the relative predictive effects of diagnosis and abuse history on health status. METHODS: Standardized measures of sexual and physical abuse history and six health status measures were estimated for the patients by diagnosis. Analysis of covariance was performed to determine the relative contributions of diagnosis type and abuse history on the health status measures…

What is the Study Design?

Calvert EL, Houghton LA, Cooper P, et al. Long-term improvement in functional dyspepsia using hypnotherapy. Gastroenterology

2002; 123: 1778-85.

• BACKGROUND & AIMS: We have shown hypnotherapy (HT) to be effective in irritable bowel syndrome, with long-term improvements in symptomatology and quality of life (QOL). This study aimed to assess the efficacy of HT in functional dyspepsia (FD). METHODS: A total of 126 FD patients were randomized to HT, supportive therapy plus placebo medication, or medical treatment for 16 weeks. Percentage change in symptomatology from baseline was assessed after the 16-week treatment phase (short-term) and after 56 weeks (long-term) with 26 HT, 24 supportive therapy, and 29 medical treatment patients completing all phases of the study. QOL was measured as a secondary outcome.

What is the Study Design?

Thomas SH, Silen W. Effect on diagnostic efficiency of analgesia for undifferentiated abdominal pain. Br J Surg 2003; 90:5-9.

• BACKGROUND: The question of whether it is safe to provide analgesia for patients with undifferentiated acute abdominal pain is marked by longstanding controversy over the possible masking of physical findings. The goal of this review is to assess the pertinent studies. METHOD: A Medline search was performed in April 2002, using the terms 'analgesia', 'abdominal pain', 'acute abdomen' and 'morphine'. Other articles were identified using the bibliographies of papers found through Medline. All articles reporting clinical trials of analgesia and its effects on diagnosis or physical examination were reviewed.

What is the Study Design?