Cohort Study

Study
Design

Step 4: Study Design

As a first step, you want to generate a solid hypothesis to guide the investigation. In order to do that, you need some background information first. Initially, you decide to contact people in the hospital to inquire about the individuals with this illness. On initial review of the cases, it does appear that a number of affected individuals did in fact work at the Glop Industries manufacturing plant. However, other individuals, not associated with the factory, are affected as well, albeit in smaller numbers. You decide to design a retrospective cohort study.

1.	Based on the facts as presented, especially the broad timing of all of the events, which do you think is the best hypothesis to investigate in this retrospective cohort study?
		a.	Those who are exposed to chemicals involved in the production of Quench-it (via direct exposure at the factory) have a higher risk of developing Susser Syndrome than those who are not exposed.
		b.	Those who develop Susser Syndrome are at a higher risk of having been involved in the production of SUPERCLEAN than those who did not develop Susser Syndrome.
		c.	Those who are exposed to chemicals involved in the production of SUPERCLEAN (via direct exposure at the factory) have a higher rate of developing Susser Syndrome than those who are not exposed.
		d.	Residents of Epiville are at higher rate of developing Susser Syndrome than the residents of the neighboring community.

Your supervisor assembles a team to begin the investigation. You must determine the available sources of information. After a little groundwork, you find that the employee health clinic at Glop Industries keeps records of comprehensive annual medical examinations of all employees beginning with their hiring date. You also learn that the factory's human resources department has records of each worker's employment position, which you can use as an indicator of the level of exposure (duration and intensity of exposure) to chemicals involved in SUPERCLEAN production. Given the availability of these data, your team decides to compare individual workers involved in the production of the SUPERCLEAN ("exposed") with workers involved with the production of other products at the factory ("unexposed"). Exposure is considered to be cumulative and will be calculated for every worker from September 1st, 2000 (time when SUPERCLEAN production started) to the present (September 1st, 2002). To simplify the study design (after all, you have just begun studies!), you decide to enroll a cohort in which all study participants enter into the study as the same time (September 1st, 2000). No individuals will be allowed to enter after the start of the study. Obviously, study participants may not be followed for the entire length of the study (2 years).

2.	Based on the above data, how should you compare the individual workers (i.e. how would you define the exposed and unexposed groups)? [See Gordis, Ch. 8, pg. 133-135]
		a.	Keep the exposure variable as dichotomous; thus, the employees involved in the production of SUPERCLEAN are exposed and those not involved in the production are unexposed.
		b.	Categorize the exposed group based on the level and duration of exposure.

Due to the complexities of quantifying chemical exposure, you decide it will be classified into 4 categories. Among the 40 job positions at the factory, only 5 positions work directly with the production of SUPERCLEAN and can be considered potentially "exposed." Additionally, after talking with some environmental experts and epidemiologists, you believe that an individual needs to have been exposed for a minimum of 6 months before a sufficient dose of the harmful chemical accumulates and any physiological changes can take place leading to the possible development of Susser Syndrome. This, you recall, is termed the induction time. This is the time between exposure and disease development during which a number of causes have to occur to result in the disease. For example, we may believe that Susser Syndrome is the result of the combination of a) exposure to a certain threshold of manufacturing chemicals; b)genetic mutation; c)a decrease in the production of a certain neurotransmitter. Thus, Susser Syndrome cannot occur until all three causes occur which may take months or even years. Any occurrence of disease within this induction period cannot be attributed to that particular exposure. Often, the induction period in an individual is unknown and we are forced to make educated guesses. For this study, you are assuming a minimal induction period of 6 months. Exposure to SUPERCLEAN production chemicals of less than 6 months will not lead to Susser Syndrome.

Therefore, you decide to define the exposed and unexposed groups as follows:

Unexposed

not working in one of the 5 positions directly involved in SUPERCLEAN production.
having worked less than 6 months in one of these 5 positions during the two-year follow-up period.

Exposed

low exposure (working 6 to 12 months in one of the 5 exposed job categories).
medium exposure (working 12 to 18 months in one of the 5 exposed job categories).
high exposure (18 to 24 months in one of the 5 exposed job categories).

You now have the basic framework of your retrospective cohort study. Your have redefined your hypothesis to incorporate your assumptions about the induction period and you have clearly defined your exposure variable and the underlying population to be sampled. You are obviously excited to get out there and begin collecting data but you have not yet finished designing the study. You must first determine who is eligible for the study.

3.	How would you define eligibility criteria for study participants? [See Gordis, Ch.8, pg. 133-135]
		a.	everyone from the selected sample is eligible
		b.	only those who have worked at the factory for at least two years AND who were shown to be healthy at their initial or annual health check-ups (mandatory for all employees of the factory) as indicated by employee medical records
		c.	exclude workers who in the last three months exhibited symptoms of the disease

Not only must the exposure variable be defined, but so too the outcome variable. Susser Syndrome is a complicated disorder with many symptoms.

4.	On what would you base your definition of Susser Syndrome? [See Gordis, Ch.3, pg. 48-51]
		a.	the neurological symptoms alone
		b.	the self-diagnosis of the participants
		c.	results of a CT scan
		d.	combination of neurological symptoms and blood test

Learning
Objectives

Introduction
to Study

Study
Design