Case-Control Study

Study Design

Now that you have thoroughly assessed the situation, you have enough information to generate some hypotheses. The two suspected causal agents of the outbreak of Susser Syndrome are Quench-It and EnduroBrick. Use the case-control method to design a study that will allow you to compare the exposures to these products among your cases of Susser Syndrome and healthy controls of your choice. From all of your class work, you know that you want your hypotheses to be as explicit and detailed as possible.

1. Based on the information you gathered, which of the following hypotheses is the most appropriate for your case-control study?

  1. (1) Those who consumed EnduroBrick are more likely to be diagnosed with Susser Syndrome than those who did not; (2) Those who consumed Quench-It are more likely to be diagnosed with Susser Syndrome than those who did not consume Quench-It.
  2. Individuals diagnosed with Susser Syndrome are more likely to have been members of the Superfit Fitness Center than individuals without Susser Syndrome.
  3. Individuals diagnosed with Susser Syndrome are likely to be exposed to a variety of different exposures than are individuals not diagnosed with Susser Syndrome
Answer (a) — correct: These hypotheses clearly state the expected causal factors (EnduroBrock and Quench-it), and the expected direction of effect. They are sufficiently explicit to allow the hypotheses to be tested after collecting data. In addition, we know that, although a case-control methodology selects individuals based on disease status and compares the exposure distribution between cases and controls, a properly conducted case-control design can compare the disease experience of the exposed to the disease experience of the unexposed.
Answer (b) — incorrect: This hypothesis is not specific enough. Affiliation with the Superfit Fitness Center is associated with many different factors. A study hypothesis should clearly define exposures and outcomes.
Answer (c) — incorrect: This hypothesis does not state a potentially causal link between exposures and outcome, and is not specific enough to allow for collected data to support or refute it.

Now that you have hypotheses, the next step is to prepare the case definition. This requires us to understand how Susser Syndrome is diagnosed. The more certain you are about your diagnosis the less error you will introduce into your study by incorrectly specifying cases. Based on information from the EDOH website, you decide that your case definition will be based on a clinical diagnosis of Susser Syndrome.

After you establish your case definition, you need to decide on the population from which the cases for your study will be obtained. Since the majority of cases from the recent outbreak were active members of the Superfit Fitness Center, you decide to base your study on this population.

Next you need to decide how you will classify your cases and controls based on exposure status. Remember, we are actually operating under two hypotheses here, each with its own unique exposure variable. Scientists working on the possible causal connection between consumption of EnduroBrick or Quench-It and the development of Susser Syndrome suggest that both exposures may have an Induction time of at least 6 months. Under this hypothesis, any cases of Susser Syndrome that occurred within 6 months of initial consumption of either EnduroBrick or Quench-It could not have plausibly been caused by the exposure. Thus, you stipulate that at least 6 months are required to have elapsed since the initial exposure, before your individual will be considered "'exposed".

Once all of these decisions have been made, it is time to create appropriate eligibility criteria for your cases and controls.

2. Which of the following do you think are the best eligibility criteria for the cases? [Aschengrau & Seage, pp. 239-243]

  1. Cases should have been members of the Superfit Center in the last two years for at least 6 months (total) and consumed either EnduroBrick or Quench-It.
  2. Cases should be correctly diagnosed with Susser Syndrome and be employed at Glop Industries.
  3. Cases should be correctly diagnosed with Susser Syndrome and have been members of the Superfit Fitness Center for at least 6 months in the last two years.
Answer (a) — incorrect: It may seem obvious but it is important to state that cases need to have been correctly diagnosed with Susser Syndrome; additionally, we are interested in determining the exposure status and thus should not require that all cases had to have been exposed. Finally, it is important to separate two exposures and to consider their effects separately.
Answer (b) — incorrect: We are interested in possible exposures at the Superfit Fitness Center and not at Glop Industries. Therefore, employment at Glop Industries should not be among the eligibility criteria.
Answer (c) — correct: We want our eligibility criteria to be as specific as possible. You have already stated the desire to limit the study to Superfit members (which will make the selection of the control group easier...see below!!); it is crucial to incorporate time elements in our study design to ensure that our exposures of interest could be plausibly associated with the development of Susser Syndrome. Without these criteria we cannot proceed to statistical analysis of the suspected associations.

Now you need to decide who is eligible to be a control.

You recall from your wonderful learning experience in P6400 that valid controls in a case-control study are individuals that, had they acquired the disease under investigation, would have ended up as cases in your study. The best way to ensure this is to sample controls from the same population that gave rise to the cases. To ensure that the controls accurately represent a sample of the distribution of exposure in the population giving rise to the cases, they should be sampled independently of exposure status.

3. Which of the following do you think are the best eligibility criteria for the controls?

  1. Controls should be residents of Epiville who have not been diagnosed with Susser Syndrome.
  2. Controls should be members of the Superfit Fitness Center who have been diagnosed with Susser Syndrome but have not consumed either EnduroBrick or Quench-It.
  3. Controls should be members of the Superfit Center for at least 6 months in the last 2 years and not be diagnosed with Susser Syndrome at the time of data collection.
Answer (a) — incorrect: While it is correct that controls should not have the diagnosis of Susser Syndrome, it is also essential that cases and controls come from the same source population. In this scenario, cases come from the population of people who attend Superfit Fitness Center, while controls come from the general population of Epiville. Since the exposures of interest are only available at the Superfit Fitness Center, selecting controls from the general Epiville population will artificially create an association between these exposures and the outcome, since the controls do not represent the exposure distribution of the source population giving rise to the cases. More simply, the controls under this scheme would not necessarily become cases if they were diagnosed with the disease, since cases are restricted to Superfit members.
Answer (b) — incorrect: Controls should not be diagnosed with Susser Syndrome. Additionally, since we are interested in the effects of exposure variables, we should not select our controls based on their exposure to EnduroBrick or Quench-It. Selection of controls must always be independent of exposure.
Answer (c) — correct: An important point is that controls should be classified as cases if they develop Susser Syndrome; in other words, controls should meet the eligibility requirements for cases except for their disease status.

Now that the eligibility criteria have been set, you must determine the specifics of the case-control study design.

How many cases and controls should you recruit?

The answer to this question obviously depends on your time and resources. However, an equally important consideration is how much power you want the study to have. Conventionally, we want a study's power to be at least 80 percent in being able to find a significant difference between the groups. Generally, if the study has less than 80 percent power, we conclude that the study is underpowered. This does not mean our results are incorrect; but if we observe an insignificant result in an underpowered study we may not be able to tell whether this is because there truly is no association or whether this is due to the lack of power in the study.

Intellectually Curious?

Learn more about power and sample size .

After crunching the numbers, you determine that the study will require the following size to achieve a desired power of 80 percent:

Number of cases: 112
Number of controls: 224
Total number of subjects: 336

Bear in mind that the study is voluntary. Subjects, even when eligible, are in no way required to participate. Furthermore, subjects may drop out of the study before completion, further decreasing your sample size. Study participation depends in large part on the methods of recruitment. In-person recruitment is generally regarded as the most effective, followed by telephone interviews, and then mail invitations. The participation rate that you expect to achieve, given your method of recruitment, will help you to calculate approximately how many individuals you will need to contact in order to meet your sample size.

Should you recruit cases and controls simultaneously or cases first and then all controls? Learn more here .