Epiville

Randomized Trials

Data Analysis

After 12 months of follow-up you finally get the results of the study. They are presented in the table below.

 Outcome Classification (after 12 months of treatment and follow-up) 
Treatment GroupProgression to Stage III Susser SyndromeNo Progression to Stage III Susser SyndromeTotal
KimFaderol Group154560
Placebo Group52860

4. Based on the table above, which of the following represents an appropriate method to analyze whether KimFaderol treatment is associated with preventing the progression to Stage III of Susser Syndrome in this population?

  1. Compare the incidence proportion of Stage III Susser Syndrome in the KimFaderol group to the incidence proportion of Stage III Susser Syndrome in the placebo group.
  2. Conduct a functional MRI scan of all individuals developing severe symptoms and compare the results of the scan between those assigned to KimFaderol and those assigned to placebo.
  3. Compare the rate of symptom appearance in the KimFaderol group to the rate of symptom appearance in the placebo group.
Answer (a) — correct: Since we are assessing whether the experimental treatment prevents the occurrence of impaired proprioception (which defines the occurrence of Stage III Susser Syndrome) we can compare the incidence proportion of new severe symptoms between the two groups.
Answer (b) — incorrect: We do not need to perform any more diagnostic tests in order to assess our hypothesis. We are interested in whether KimFaderol prevents impaired proprioception (as assessed by the neurologist), and do not need a fMRI to tell us this.
Answer (c) — incorrect: We have no information on person-time of observation, and no information on the time of occurrence of symptoms, since we assessed outcome only once, 12 month after the start of the treatment. Therefore we cannot calculate rates.

5. Perform the following calculations:

a. Calculate the incidence proportion of Stage III Susser Syndrome in the KimFaderol group to 2 decimal places. Answer — 0.25
b. Calculate the incidence proportion of Stage III Susser Syndrome in the placebo group. Answer — 0.87

6. Are one or both of the following answers correct concerning what you can conclude by comparing the two incidence proportions calculated above?

  1. Only the following statement: The incidence of Stage III Susser Syndrome is 3.5 times higher in the placebo group compared with the KimFaderol group.
  2. Only the following statement: The incidence of Stage III Susser Syndrome is 62% less in the KimFaderol group compared with the placebo group.
  3. Both A and B are correct.
Answer (a) — incorrect: While the above is true, comparing the ratio of the incidence proportion in the placebo group to the KimFaderol group, other answers are also correct.
Answer (b) — incorrect: While the above is true, comparing the difference between the incidence proportion in the placebo group and the KimFaderol group, other answers are also correct.
Answer (c) — correct: Choice A compares the ratio of incidence proportions (the Risk Ratio) in the two treatment groups, while choice B compares the difference between incidence proportions (the Risk Difference) in the two groups. The Risk Ratio is often used to evaluate the strength of the association, while the Risk Difference is often used to measure the public health importance of a given association. Thus, they are both important in the evaluation of the results of the study.

You give the results of this analysis to your supervisor. However, she is concerned that you have underestimated the "true effect" of the drug on preventing the development of Stage III Susser Syndrome. She argues that you have included all individuals who were assigned to take the drug, but not all of these individuals actually took it. Since data were collected on the actual intake of the prescribed treatments by each participating individual in both arms of the study, your boss suggests doing an analysis by excluding those individuals who did not take their assigned treatment.

As a student of Principles of Epidemiology, you are hesitant to analyze the data in this way. The data on KimFaderol provided by the manufacturer show that individuals who consume large amounts of alcohol may have severe side effects if given the drug. There is concern that these side effects may prevent some individuals from complying with their treatment assignment. In addition, alcohol consumption is known to complicate Susser Syndrome, such that individuals who drink regularly are at higher risk for developing Stage III Susser Syndrome than are individuals who do not drink regularly.

You look into the data and see that, while all individuals in the placebo arm were compliant with their treatment, 10 of the 60 individuals in the KimFaderol arm were non-compliant. Eight of these individuals were classified as having Stage III Susser Syndrome, while the other 2 were not.

7. If you were to exclude the noncompliant individuals from your analysis, what would the new ratio be comparing the incidence of Stage III Susser Syndrome among those who actually took placebo to the incidence of Stage III Susser Syndrome among those who actually took KimFaderol?

Answer: Answer — 6.19

[ Interactive Exercise ] Click here for an interactive explanation of why the results of "Intent-to-Treat" analysis often differ from "compliance" analyses.

8. What is the purpose of Intent-to-Treat analysis?

  1. To ensure a valid comparison between those who actually took the drug and those who did not.
  2. To maintain the comparability between the treatment and exposure groups that was obtained through randomization.
  3. To ensure comparability between the treatment groups at baseline.
Answer (a) — incorrect: Intent-to-Treat compares individuals based on treatment assignment, regardless of whether or not they actually took the drug.
Answer (b) — correct: Not using Intent-to-Treat analysis means that the investigator is no longer assigning the exposure, and the "experimental" nature of the design is thus compromised. As a result, comparison groups may no longer be comparable with regard to different characteristics.
Answer (c) — incorrect: This is the purpose of randomization.