retrospective & prospective studies case studies
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Retrospective & Prospective Studies Case Studies. ICRI Delhi. Hierarchy of Evidence. Anecdotal case reports Case series without controls Series with literature control Analyses using computer databases Case control studies Cohort studies Randomized control trials (RCTs) - PowerPoint PPT PresentationTRANSCRIPT
Retrospective & Prospective Studies
Case Studies
ICRI Delhi
Hierarchy of Evidence
1. Anecdotal case reports2. Case series without controls3. Series with literature control4. Analyses using computer databases5. Case control studies6. Cohort studies7. Randomized control trials (RCTs)8. Meta-analysis with original data
Evidence PyramidEvidence Pyramid
Study DesignStudy Design
• Experimental Study
(Controlled Controlled AssignmentAssignment)• RCT (randomized
person assignment)
• Cluster trial (randomized cluster assignment)
• Observational Study
(Uncontrolled Assignment)• Cohort studies (sampling
with regard to exposure)• Cross-Sectional• Case-Control (sampling
with regard to disease or effect)
Study Designs
Experimental Observational
DescriptiveAnalytical
Case-Control Cohort
+ cross-sectional & ecologic
(RCTs)
Descriptive studiesDescriptive studies
Examine patterns of disease
Analytical studiesAnalytical studies
Studies of suspected causes of diseases
Experimental studiesExperimental studies
Compare treatment modalities
Purpose of Studies
Algorithm for classification
of types of clinical
research
ObservationalObservational Studies Studies(no control over the circumstances)
- Descriptive: Most basic demographic studies
- Analytical: Comparative studies testing an hypothesis
* Cross-sectional (a snapshot; no idea on cause-and-effect
relationship) * Cohort (prospective; cause-and-effect relationship can be
inferred) * Case-control (retrospective; cause-and-effect relationship can be
inferred)
•Descriptive studies do not feature a comparison (control) group.
•Descriptive studies are often the first foray into a new area of medicine.
•They describe the frequency, natural history, and possible determinants of a condition.
•Hypothesis generation about the cause ot the
disease.
Types of clinical research
Case report Case-series reports
Good descriptive reporting answers the five basic
W questions:
Who, what, why, when, where
Descriptive studies
Case report
Case-series reports
Surveillance studies / Surveys / Cross-sectional studies
And a sixth: so what ?
Who has the disease in question ? What is the condition or disease being studied ? Why did the condition or disease arise ? When and Where does or does not the disease or condition arise ?
Case reports and series
• Case report: describes an observation in a single patient.– “I had a patient with a cold who drank lots of
orange juice and got better. Therefore, orange juice may cure colds.”
• Case series: same thing as a case report, only with more people in it.– “I had 10 patients with a cold who drank
orange juice….”
Value of case reports/series
• May generate a hypothesis: “maybe orange juice cures colds….”
• Weakness: cannot test the hypothesis– no control group– often too few people to make generalizations
Analytical Studies
Retrospective & Prospective Studies
AnalyticalAnalytical Studies Studies
(comparative studies testing an hypothesis)
* Cohort (prospective)
Begins with an exposure (smokers and non-smokers)
* Case-control (retrospective)
Begins with outcome (cancer cases and healthy controls)
* Cross-sectional (concurrent)
Exposure & outcome co-exist
Cross-sectional Study
Exposure
Outcome
300 men MI Next door neighbour
Mean S-cholesterol Mean S-cholesterol
256 mg/dl 202 mg/dl
at the same time
Cross-Sectional Study
•Ask each person about both exposure and disease at that point in time.
•Investigator gathers data only at that one point in time.
•Disease rate in exposed group is compared to disease rate in unexposed group.
•Select a study sample.
Data Gathering Approaches
-Person-to-person interviews or surveys, mailed questionnaires, telephone interviews etc.
Cross-Sectional StudyAdvantages
•One stop, one time•Less expensive
•Useful for planning services
•Shows relative distribution of conditions
•Shows interrelatedness of attributes and conditions•Does not rely on individuals who present for medical treatment •No one exposed to harmful causal agent because of study
Cross-Sectional Study
Disadvantages
•Only representative of participants
•Not effective if disease is rare
•May not be representative of all cases
•Cause and effect uncertain because exposure and disease are measured simultaneously
• Cannot be used for hypothesis testing
Ovarian cancer
Use of oral contraceptives
Control group
Case Control & Cohort Studies
Case-control study
Study Population
Cases
Controls
Exposed
Non-exposed
Exposed
Non-exposed
Schematic diagram of a case control study design
Bias in Case-Control studies
• Selection bias
• Confounding bias
• Berkesonian bias
• Observation bias
• Recall Bias: Cases are more likely to remember exposure than controls
• Non response
Question
• In a study on the association between smoking and CHD, 200 CHD patients were selected from a hospital OPD and 400 similar controls were enrolled. History of patients revealed that there were 112 smokers in the CHD group as compared to 176 in the control (non CHD) group. Comment on the association between smoking and CHD.
400200Total
22488Non-smoker
176112SmokerExposure Status
No CHD
(Controls)
CHD cases
(Cases)
Disease Status
Calculating the Odds Ratio
Odds Ratio = =AD
BC
112 x 224
176 x 88= 1.62
Interpreting the Odds Ratio
or
The odds of exposure for cases are 1.62 times the odds of exposure for controls.
Those with CHD are 1.62 times more likely to be smokers than those without CHD
or
Those with CHD are 62% more likely to be smokers than those without CHD
Cohort study / Follow-up study
Study population
Exposed
Non-exposed
Disease +
Disease +
Disease -
Disease -
Cohort StudiesCohort Studies
time
Exposure Study startsDisease
occurrence
Prospective cohort studyProspective cohort study
time
ExposureStudy startsDisease
occurrence
Radiation Leak in Nuclear Plant
12 workers on site at time of the leak
24 workers off duty at home at time of the leak
Cohort Workers1969
Workers disease status1999
4 with leukemia
8 no leukemia
4 with leukemia
20 not leukemia
Exposed
Unexposed
Retrospective cohort studiesRetrospective cohort studies
Exposure
time
Diseaseoccurrence Study starts
Radiation Leak in Nuclear Plant
12 workers on site at time of the leak
24 workers off duty at home at time of the leak
Cohort of Workers 1999 collect info from1969
Workers disease status1999
4 with leukemia
8 no leukemia
4 with leukemia
20 not leukemia
Exposed
Unexposed
Nested case-control studies
• Cases and controls come from a well-defined population.
• Combine many of the strengths of retrospective cohort and case-control studies.
Prospective vs. Retrospective Cohort Studies
• Prospective Cohort Studies– Time consuming, expensive– More valid information on exposure– Measurements on potential confounders
• Retrospective Cohort Studies– Quick, cheap– Appropriate for examining outcomes with long
latency periods– Difficult to obtain information of exposure– Risk of confounding
The Framingham Study
• Since 1948, samples of residents of
Framingham, Massachusetts, have
been subjects of investigations of risk
factors in relation to the occurrence of
heart disease and other outcomes
The Framingham Study• Hypotheses:
– Persons with hypertension develop CHD at a greater rate than those who are normotensive.
– Elevated blood cholesterol levels are associated with an increased risk of CHD.
– Tobacco smoking and habitual use of alcohol are associated with an increased incidence of CHD.
– Increased physical activity is associated with a decrease in development of CHD.
– An increase in body weight predisposes a person to CHD.
The Framingham Study
• Study population consisted of 5,127 men and
women between ages 30 and 62 years and were at
the time of entry free of cardiovascular disease
(1948-1952)
• Cohort was examined every 2 years and by daily
surveillance of hospitalizations at Framingham
Hospital
The Framingham Study• Exposures included:
– Smoking
– Alcohol use
– Obesity
– Elevated blood pressure
– Elevated cholesterol levels
– Low levels of physical activity, etc.
Comparison (Control) Groups• With a one-sample (population-based) cohort,
exposure is unknown until after the first period of observation
– Example: • Select the cohort (all residents of Framingham) • All members of the cohort are given questionnaires,
and/or clinical examinations, and/or testing to determine exposure status
• The cohort is then divided into exposure categories based on those results
Comparison (Control) Groups
• The nonexposed become the internal controls
• For continuous variables, such as caloric intake or amount of exercise, multiple levels of exposure are constructed
• It is common to break exposure into quantiles (equally ordered subgroups) and to use the extremes as the comparison (referent) group
Question
How does the design of a cohort study change if everybody in the cohort is exposed (special exposure cohort)?
Example: All persons exposed to radiation from the Chernobyl accident.
Answer
• You need to select a separate control cohort people as similar as possible to the exposed cohort (income, age, gender, employment) but with no exposure
• If you cannot find a comparison group, you may use available population incidence rates under certain circumstances
Question
• In a study on association between smoking and CHD, 288 smokers and 312 nonsmokers, i.e a total of 600 subjects were enrolled. selected from a hospital OPD and 400 similar controls were enrolled. The subjects were followed up and 112 smokers developed CHD while 88 nonsmokers also developed CHD. Comment on the association between smoking and CHD.
224
176
No CHD
31288Non-smoker
288112SmokerExposure Status
TOTALCHD
Disease Status
Example: Calculating the Relative Risk
Relative Risk = =A/(A+B)
B/(C+D)
112 / 28888 / 312
= 1.38
Example: Interpreting the Relative Risk
Relative Risk = 1.38
The risk of developing CHD is 38% higher for a smoker than for a nonsmoker.
The risk of developing CHD is 1.38 times higher for a smoker than for a nonsmoker.
or