Research designs: Observational and experimental studies

Basics of Scientific researchClass #3

Ekaterine Karkashadze, MD, MS

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Study

Scientific Research

Gathering valid and precise data on the relationship between exposure and health related state or

event (causes, prevention and treatment of disease)

Surveillance

Monitoring aspects of disease occurrence and

spread

Definition of Cause

• “An event, condition or characteristic that preceded disease event and without which the disease event would not have occurred, or would not have occurred until some later time” (by Rothman and Greenland)

• “Something that makes a difference” (by Susser)

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How do we know that something causes a certain condition?

▪ Scientists test hypothesis by making comparisons. Example:

Comparing death rates from lung cancer between people exposed to high levels of air pollution and those exposed to low levels of air pollution.

Results: Among people exposed to high levels of air pollution death rates from lung cancer are twice the rates of those exposed to low levels

Conclusion: High levels of air pollution is associated with higher rates of death from lung cancer

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Association necessary but not enough for the factor to be a cause of disease

• There is an association between rooster’s crowing at sun rise..

• Does rooster causes sun to rise?

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Characteristics of cause

Three essential attributes of cause:

• Association

• Time order

• Direction

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1. Association

“Statistical dependence” between causal factor and effect (event, outcome)!

• Associations are measured in analysis after comparison of two or more groups

Hammond and Horn found in the cohort study that “the death rate from lung cancer was much higher among men with a history of regular cigarette smoking than among men who never smoked regularly.”

These two researchers finally felt they had the convincing evidence that cigarette smoking was a cause of lung cancer that the world was previously lacking.

No association - causality rejected!8

2. Time order

Cause MUST precede the effect (event, outcome)!

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Alcohol intake during pregnancy

Birth defects

Exposure to virus Viral infection

3. Direction

• Asymmetrical relationship between the cause and the effect (event, outcome)!

X Y (Causal relationship)

A B (Non - causal relationship)

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Observational & Experimental studies

• Observational study – conducted in natural environment

• Experimental study – conducted in experimental environment

They represent different ways of harvesting information on the relationship between the exposure and the outcome

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Observational studies

• Observational study - the study without any forced change to the circumstances, or without any intervention

e.g. we measure members of a sample without trying to affect them.

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Types of observational studies

• cohort studies

• case-control studies

• cross-sectional studies

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Observational study

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Framingham Heart Study

• Ongoing cardiovascular cohort study of residents of the city of Framingham, Massachusetts, began in 1948 with 5 209 adults from Framingham.

• The project of the National Heart, Lung, and Blood Institute, in collaboration with (since 1971) Boston University.

• The Framingham Heart Study participants, and their children and grandchildren, voluntarily consented to undergo a detailed medical history, physical examination, and medical tests every 3 to 5 years, creating a wealth of data about physical and mental health, especially about cardiovascular disease.

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Major findings from Framingham Study

• 1960s– Cigarette smoking increases risk of heart disease.

• 1970s– Elevated blood pressure increases risk of stroke. In women who are

postmenopausal, risk of heart disease is increased, compared with women who are premenopausal.

• 1980s– High levels of HDL cholesterol reduce risk of heart disease. No empirical evidence

found to confirm the rumor that filtered cigarettes lower risk of heart disease as opposed to non-filters.

• 2000s– Obesity is a risk factor for heart failure. 17

Advantages of observational studies

• Can be used to study the effects of wide range of exposures, including effects of hazardous agents

• Relatively cheap (less expensive) than experimental study

• Helpful to study disease frequency (incidence, prevalence) and determinants of disease progression, to predict future healthcare needs etc.

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Major Limitation

• Susceptible to extraneous factors that distort true association between exposure and outcome

– This extraneous factors are termed bias and confounding

– If bias and confounding is not appropriately addressed, this may lead biased results, i.e. incorrect or invalid interpretation of results related to cause leading (or not leading) to a certain outcome

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Experimental studies

• Experimental study - the study with forced change to the circumstances, or with introduction of an intervention

e.g. we assign people or things randomly to different groups (experimental/treatment & control groups) in order to determine the causal effect of a certain condition on a certain outcome.

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Experimental study

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The main application of experimental studies in medicine

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in evaluating therapeutic (or prevention) interventions

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randomized controlled trials

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PROGRESS study

• The research question: Does the use of Perindopril (+/-Indapamide) in patients with a history of cardio-vascular attack lead to decreased risk of future stroke?

• Enrollment: 1995-2001

Patients were randomized to perindopril group (n = 3 051) vs placebo (n =3054).

• Primary outcome: Repeat stroke

• Findings: Treatment with combination therapy with Perindopril and Indapamide decreased blood pressure and recurrence of stroke (as compared to placebo group).

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Advantages of experimental studies

• Most rigorous study design and high degree of validity due to randomization

• The gold standard for clinically testing treatments and drugs

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Limitations

• Not always feasible to conduct experimental studies because of ethical considerations: not acceptable to expose subjects deliberately to potentially serious hazards.

• High number of noncompliance, lost to follow-up might undermine validity

• High cost

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Important note

• Observational studies are no less necessary than experimental studies!

• A choice depends on a research question and practical considerations!

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Observational or Experimental?

A study took random sample of adults and asked them about their bedtime habits. The data showed that people who drank a cup of tea before bedtime were more likely to go to sleep earlier than those who didn't drink tea.

Which type of study is this?

A)Observational

B)Experimental

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Observational or Experimental?

A study randomly assigned volunteers to one of two groups:One group was directed to use social media sites as they usually do.One group was blocked from social media sites.The researchers looked at which group tended to be happier.

Which type of study is this?A)ObservationalB)Experimental

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Questions?

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Homework

• Reading from the course book (Ann. K. Allen. Research skills for Medical Students.SAGE Publication Inc. 2012)

• Pages 20-30

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