Research Methods: RCTs, Variables, and Study Design

Learning Objectives

• Experimental study design terms that need defining include variables (dependent, independent, confounding), random assignment, and control.
• The three characteristics of a true experiment should be identified.

Research Study Design

• Research design can be classified by study purpose, time orientation, and experimental setting.
• Study purposes can be descriptive or analytical.
• Time orientation can be prospective or retrospective.
• Experimental settings can be experimental or observational.

Study Designs

• Observational studies include case reports/series, cross-sectional studies, case-control studies, and cohort studies.
• Experimental studies include randomized controlled trials (RCTs), sometimes referred to as randomized clinical trials.

Important Terminology: "Variables"

• Variables are characteristics that can vary.
• Variables are the "building blocks" of research questions and protocols.
• A variable represents a concept, factor, element, or feature that can have more than one value.
• Examples are drug dose and outcomes (e.g., weight, HbA1c level).

Pose A Research Question and Hypothesis

• A Research Question states the research problem to be studied.
• For instance: "In patients with diabetes, do clinical services by pharmacists improve short-term clinical outcomes compared with traditional care in an outpatient setting?"
• A Hypothesis specifies an expected relationship that is being evaluated between intervention and outcome or two or more variables.
• For instance: "Clinical services by pharmacists will improve short-term clinical outcomes in patients with diabetes in outpatient settings compared to traditional care."

Independent Variable

• An independent variable’s value is not dependent on that of another variable.
• It is a condition, intervention, or characteristic that will predict or cause a given outcome.
• It is the variable you have control over, what you can choose and manipulate.
• It usually affects the dependent variable.

Dependent Variable

• A dependent variable responds to the independent variable and "depends" on it.
• The outcome variable is the same as the dependent variable.
• It is a response or effect that is presumed to vary depending on the independent variable.

Independent and Dependent Variables

• The independent variable is the cause.
• The dependent variable is the effect/outcome.

Extraneous & Confounding Variables

• An extraneous variable is a factor not directly related to the study's purpose but may affect the dependent variable.
• A confounding variable (or factor) is an extraneous variable that correlates with both the dependent variable and the independent variable.

Confounding Variable Examples

• The rate of drowning deaths increases sharply as ice cream sales increase.
• A conclusion that ice cream consumption causes drowning would be an example of a confounding variable.
• Since the 1950s, both atmospheric CO₂ levels and obesity levels have increased sharply. A conclusion that atmospheric CO₂ causes obesity would be an example of a confounding variable.

A Confounding problem in research

• Observational studies such as the Nurses Health Study suggested a cardiovascular protective benefit of hormone replacement therapy (HRT) for postmenopausal women.
• Randomized, controlled trials such as the Women's Health Initiative and the Heart and Estrogen/Progestin Replacement Study pointed to no benefit, or even harm from HRT.

Confounding Variable: HRT Example

• Observational studies have demonstrated that women who have used postmenopausal hormone replacement therapy (HRT) are at reduced risk of coronary heart disease. A conclusion that HRT reduces the risk of coronary heart disease is an example of a confounding variable.
• When confounding variables are not controlled, they exert a contaminating influence on the independent variable and obscure its separate effects.
• Experiments are designed to control for this type of confounding.

How to Design a Perfect Experiment

• Randomized controlled trials follows a true experimental study design, and is the most rigorous form of scientific investigation for testing hypotheses. They are considered the gold standard for clinical research.
• The purpose of an experiment is to support a cause-and-effect relationship between a particular action/condition (independent variable) and an observed response (dependent variable).

Characteristics of Experiments

• For a study to be considered a true experiment, it must have three essential characteristics:
• The independent variable must be manipulated by the experimenter.
• The subjects must be randomly assigned to groups.
• A control group must be incorporated within the design.

Manipulation of Variables

• Manipulation of variables refers to a deliberate operation performed by the experimenter.
• The experimenter imposes a set of predetermined experimental conditions (the independent variable) on at least one group of subjects, often by administering the intervention to one group and withholding it from another.
• The experimenter can also manipulate the levels of the independent variable, such as assigning subjects to varied drug doses.

Random Assignment

• Random assignment means that each subject has an equal chance of being assigned to any group.
• Assignments will be independent of personal judgment or bias.
• With randomization, different groups will achieve equivalence. Inter-subject differences should balance out.
• If groups are assumed to be equivalent at the start of an experiment, there is confidence that differences observed at its end are not due to subject variability that existed before it began.

Control Groups

• A control group, along with random assignment, is an effective way of ruling out extraneous effects.
• Subjects in a control group may receive a placebo, no treatment, different dose, or standard care, and will act as a basis of comparison for a new intervention.
• To draw valid comparisons, an assumption of a reasonable degree of equivalence between the control and experimental groups must be made.

Placebo

• A Placebo is a substance or treatment with no active therapeutic ingredients.
• Examples are: saline solution, lactose capsules
• A Placebo may have a therapeutic effect based solely on the power of suggestion (placebo effect).

Control Groups: Constraints

• The use of a placebo or no treatment control is sometimes unfeasible for practical or ethical reasons.
• Clinical researchers often evaluate a new experimental treatment against conventional methods of care. This approach assesses whether the new treatment is more effective than standard methods, but does not diminish the validity or usefulness of the study.

Experiments

• Experiments are based on a logical structure (or design) within which the investigator systematically introduces changes into natural phenomena and then observes the consequences of those changes.
• The essence of an experiment lies in the researcher's ability to manipulate and control variables to rule out rival hypotheses as possible explanations for the observed response.

Reality Check

• In reality, clinical experiments seldom completely eliminate confounding effects.
• Even though causality can never be demonstrated with complete certainty, the experimental method provides the most convincing evidence of the effect one variable has on another.