Epiville

Randomized Trials

Study Design

Since there is currently no treatment for Susser Syndrome available, and since KimFaderol is not yet on the market, the only way patients will potentially have access to this treatment is by enrolling in this study.The researchers are using a randomized, placebo-controlled, double-blind trial to test the effectiveness of the drug in preventing the loss of proprioception, the most severe consequence of Susser Syndrome, in patients with stage I or II of the disease over a 12-month period of follow-up. This follow-up period was chosen to allow for sufficient time for individuals to progress to Stage III while minimizing the costs and complications associated with a longer-duration study.

Before you begin enrollment in the study, your boss asks you to prepare all of the information you will need to give to prospective subjects so they can give their informed consent (or refusal) to participate in the study. As you might expect, there is a great deal of information that needs to be disseminated to potential study participants to allow them to make an informed decision about participation in the study. There is also quite a bit of administrative work that needs to be done before the study begins.

1. Based on the facts presented, which do you think is the best hypothesis to study in this randomized trial?

  1. Individuals randomized to receive KimFaderol will be more likely to be cured of Susser Syndrome than will individuals randomized to placebo
  2. Individuals randomized to receive KimFaderol will have a lower risk of being diagnosed with Susser Syndrome than will individuals randomized to receive placebo
  3. Individuals with Stage I or II Susser Syndrome randomized to receive KimFaderol will be less likely to develop impaired proprioception than will individuals with Susser Syndrome randomized to receive placebo
Answer (a) — incorrect: Since KimFaderol is designed to prevent the onset of Stage III of Susser Syndrome (characterized by severely impaired proprioception), but does not claim to cure the disease, we would not expect KimFaderol treatment to lead to cure.
Answer (b) — incorrect: Everyone in this study has already been diagnosed with Stage I or Stage II Susser Syndrome.
Answer (c) — correct: This hypothesis specifies (1) the exposure groups (KimFaderol and placebo), (2) the outcome under study (impaired proprioception, (3) the population of interest (individuals diagnosed with Susser Syndrome but not yet experiencing impaired proprioception, and (4) the expected direction of effect.

[ Interactive Exercise ] This exercise describes the purpose of randomization.

2. What is the primary purpose of randomization in the study design as outlined above?

  1. The biggest strength of the randomized trial design is the experimental manipulation (randomization) of the treatment of interest such that all other causes of disease are equally distributed between those who receive the treatment and those that do not. Thus, treatment will not be associated with any other risk factors for disease (see interactive exercise above for more!)
  2. To ensure that individuals in both the treatment and placebo groups actually take the drug that they are administered
  3. To ensure that the clinicians and study investigators are unaware of the exposure status of the individuals in the study
Answer (a) — correct: One of the biggest strengths of a randomized trial design is its experimental manipulation of the treatment of interest, such that treatment assignment is, on average, not associated with other risk factors for the outcome under investigation. (See interactive exercise above for more!)
Answer (b) — incorrect: Unfortunately, randomization cannot guarantee that individuals actually take the treatment that they are randomized to receive.
Answer (c) — incorrect: This is the purpose of blinding in a randomized trial, not the purpose of randomization. (Blinding prevents clinicians from assigning treatment differentially based on knowledge of treatment assignment.)

3. What is the purpose of placebo control in the study design as outlined above?

  1. To ensure that the clinicians and study investigators are unaware of the exposure status of the individuals in the study
  2. To account for the "placebo effect" and to minimize the possibility that individuals in the study know what treatment they have been assigned to
  3. To ensure that individuals in both the treatment and placebo groups actually take the drug that they are administered
Answer (a) — incorrect: While placebo control can aid in masking the exposure status of individuals to the researchers, it is not sufficient to do so. This requires blinding.
Answer (b) — correct: Using a placebo control serves the dual role of accounting for the possibility that individuals who believe they are receiving the study drug will show a beneficial effect of treatment (the "placebo effect") and to prevent individuals from actually knowing whether they are taking an active treatment or not.
Answer (c) — incorrect: Although having a placebo which looks very much like the "active" drug may aid in compliance, it cannot guarantee that individuals actually take the treatment that they are randomized to receive.

Intellectually curious?

Learn more about the use of placebo in randomized trials, and the controversy surrounding when it is ethical to do so.