Chapter 13

Experimental Studies

Overview

An experimental study assigns participants to intervention and control groups in order to examine whether an intervention causes an intended outcome.

Because the researcher assigns participants to receive a particular exposure, the exact timing, dose, duration, and frequency of the exposure are known.

FIGURE 13-2 Framework for an

Experimental Study.

RCTs

In a randomized controlled trial (RCT):•Some participants are randomly assigned to an active intervention group•The remaining participants are assigned to a control group•All participants from both groups are followed forward in time to see who has a favorable outcome and who does not

Describing the Intervention

The research plan should carefully define:•What the intervention will be•Where and how participants will receive the intervention•When, how often, and for what duration participants will receive the intervention•Eligibility criteria for participants

Defining Outcomes

Most experimental studies are superiority trials that aim to demonstrate that a new intervention is “better” than some type of control.

Because the term “better” can be defined in so many ways, the researcher must carefully define what constitutes a favorable outcome for the experiment.

FIGURE 13- 3 Types of Success

FIGURE 13- 4

Examples of

Favorable Outcomes

Selecting Controls

Experimental studies usually assign some participants to the active intervention and the remainder to a control group•The most typical control is a placebo, an inactive comparison that is similar to the therapy being tested•Sometimes the new therapy is compared to some existing “standard of care” or other therapy•Sometimes varying doses and durations of a therapy may be compared to one another

FIGURE 13- 5 Examples of Types of Controls

FIGURE 13- 5 Examples of Types of Controls

Hawthorne bias

Hawthorne effect: participants in a study may change their behavior for the better simply because they know they are being observed

This may interfere with the accurate measurement of the impact of the new intervention.

Blinding

Blinding = masking = participants in an experimental study do not know whether they are in the active intervention group or the control group•In a single-blind study, participants are unaware of their exposure status•In a double-blind study, neither the participants nor the persons assessing the participants’ health status know which participants are in the active and control groups. Blinding minimizes information bias

Randomization

A variety of approaches can be used to randomly allocate participants to an active intervention group or a control group, such as:•Simple randomization•Block randomization•Stratified randomization

FIGURE 13- 6 Examples of Types of Randomization

Ethical Considerations

Experimental studies involve a particularly high level of ethical risk because the researcher assigns participants to exposures that the participants do not choose and may have been unlikely to encounter in normal life had they not volunteered to participate in a research project.

Ethical Principles

• Equipoise: experimental research should be conducted only when there is genuine uncertainty about which treatment will work better

• Distributive justice: infers that the source population must be an appropriate and non-exploitative one

• Beneficence (do good) and nonmaleficence (do not harm): researchers must balance the likely benefits and risks of the study

Ethical Principles

• Respect for persons:– Participants must volunteer for a study without

being unduly influenced by the prospect of being compensated for their participation

– Participants must be able to understand what it means to be a research subject, including the possibility of being assigned to a control group instead of the new intervention

FIGURE 13- 7 Examples of Ethical Issues to Consider When Planning an

Experimental Study

Analysis

Experimental studies use many of the same measures of association that cohort studies do:•Relative rates (RRs)•Attributable risks (ARs, AR%s)•Measures of survival

Experimental studies use these measures to examine the impact of an assigned exposure on the likelihood of having either a favorable or unfavorable outcome.

Analysis: Efficacy

Efficacy: the proportion of individuals in the control group who experience an unfavorable outcome who could have been expected to have a favorable outcome had they been in the active group instead

A high efficacy is an indicator that an intervention is successful.

Analysis: NNT

Number needed to treat (NNT): the expected number of people who would have to receive a treatment to prevent an unfavorable outcome in one person (or, alternately stated, to achieve a favorable outcome in one person)

A small NNT indicates a more effective intervention.

Analysis: NNT

• If a drug is intended to prevent stroke and has an NNT of 5, then 5 people have to take the drug for one year (or some other specified time period) to prevent one of the 5 from having a stroke.

• If a drug has an NNT of 102, it means that 102 people have to take the drug to prevent one of the 102 from having a stroke.

FIGURE 13- 8 Efficacy and Number Needed to Treat (NNT)

Analytic Frameworks

• Treatment-received approach: limit analysis to the participants who were fully compliant with their assigned intervention

• Treatment-assigned approach (intention-to-treat approach): includes all participants even if they were not fully compliant with their assigned intervention

FIGURE 13- 9 Flow of Participants in an Experimental Study

Screening & Diagnostic Tests

• The goal of some studies is to compare two tests that are supposed to measure the same thing, such as comparing the results of an antibody test for cancer to biopsy results

Screening & Diagnostic Tests

• Sensitivity = Of those who have the disease, what % test positive?

• Specificity = Of those who do not have the disease, what % test negative?

Screening & Diagnostic Tests

• Positive predictive value (PPV) = Of those who test positive, what % actually have the disease?

• Negative predictive value (NPV) = Of those who test negative, what % actually do not have the disease?

FIGURE 13- 10 Test

Results

Tests of Agreement

• Tests of inter-observer agreement (also called concordance) can be used to determine the extent of agreement between two assessors who are evaluating the same study participants

• For example, a measurement known as the kappa statistic can indicate whether two radiologists examining the same set of X-rays reach the same conclusion about the presence or absence of a fracture more or less often than can be expected by chance