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L9_followup_studies_ADA.pptxFollow-Up Studies
Aka Cohort Studies
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In this lecture, we begin learning about analytical epi designs. Recall these are TRUE epi designs in that they are observational rather than experimental…
Lesson Overview
Overview of follow-up studies
Advantages
Disadvantages
Types of follow-up studies
Prospective
Retrospective
Exposure status
Analysis
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F-up Overview
Also called:
Longitudinal Study
Span long periods of time
Cohort Study
Follows a defined group of people over time
Follow-up studies are also sometimes called "longitudinal" studies in that they are conducted over a long period of time. They are also commonly called “cohort” studies because they follow a defined group of people ( a “cohort” ) over time.
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Advantages of F-up Studies
Direct measurement of incidence in E+ and E-
Can study multiple outcomes
Different diseases developed
Different causes of death
Knowledge of exposure precedes disease
Good for rare exposures
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Follow-up studies are the “gold standard” when exploring the association between a risk factor (or in prevention studies, a health-enhancing factor), and health status outcomes or health events. Like the name implies, this type of study “follows up” on people, based on their exposure status, as they progress through time. Because of this, f-up studies can:
assess multiple outcomes (effects) of a single exposure
assess the temporal relationship between exposure and disease
If prospective, minimize bias in the ascertainment of exposure status
Allow direct measurement of incidence of disease in the exposed and non exposed population
F-up studies are good for determining the health outcomes of rare exposures because the “starting point” is the exposure status.
Starts with Exposure
As mentioned on the previous slide, follow-up studies select study subjects based on exposure status. At time zero, the two groups – the exposed and the unexposed – are all disease free. Each group is then followed through time to determine the occurrence of the disease (incidence) or death (mortality) from it.
F-up studies allow us to compare the incidence of the disease in an exposed population to the incidence of disease in an unexposed population. As such, f-up studies estimate the magnitude of an association between exposure and disease, and indicates the likelihood of developing the disease in the exposed group relative to those who are not exposed. A classic example is cigarette smokers: cigarette smokers are 9-10 times more likely to develop lung cancer than non smokers.
(CCD, recall, is common closing date – or when the study ends).
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Follow-Up Ends for a person when
She/he gets the disease of interest (or, in mortality studies, dies from it)
She/he dies (from any cause)
She/he becomes "lost to follow-up”
the common closing date (CCD) is reached
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In a f/up study, the follow up on an individual subject ends when she/he:
gets the disease of interest (or, in mortality studies, dies from it)
2) dies (from any cause)
3) becomes "lost to follow-up" (so that information on D+ or D- is no longer available)
Does this look familiar? =)
Otherwise, follow-up for the study ends on the common closing date (CCD) designated by the investigator.
Cases that occur after the CCD do not count as D+. THIS IS IMPORTANT TO REMEMBER!!
Commit the information on this slide to memory!!!
Disadvantages of F-up Studies
Expensive
Long study period
Not good for rare disease
Limited number of exposures
Losses to follow up
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Difficulties or problems with all f/up studies:
1.For a rare disease, in order to observe any incident (D) cases, your must observe a whole lot of people and/or follow them for a great length of time.
2. Choice of so-called E- group is not always straight forward (this is an example of selection bias and is a factor that affects validity). E- groups can be:
a) external comparison group -- people with characteristics that are different (geographic, racial, etc.) than those of the E+ group. This, potentially, reduces the comparability between the two groups with respect to other factors (known as confounding).
b) internal comparison group -- people from within the same group who we believe -- or who claim to be -- unexposed. The problem here is that there is no way to know whether or not they were, perhaps, exposed at a lower level.
3. Loss to follow up – sometimes more than 30 to 40% (increases with length of study period); this attrition introduces bias and can weaken the validity of the study.
4. Nonparticipation – introduces concerns regarding ability to generalize findings
Follow-Up Studies Can Be...
Prospective (concurrent)
Retrospective (nonconcurrent)
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F/up studies can be:
1) Prospective (aka "concurrent"): follow-up period begins today and extends into the future; or,
2) Retrospective (aka "nonconcurrent"): follow-up period begins at some point in the past and ends in the past.
Prospective F/Up Study
Epidemiologist starts at time zero
Groups based on exposure status
Everyone is D-
Everyone is followed through time
CCD
Disease status assessed
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In a prospective f-up study, the epidemiologist starts at time zero, which is when the exposure occurs, and groups people based on their exposure status. For example, let’s say there was a chemical spill in a factory and all of the employees who worked the first shift were exposed, but those who worked the third shift were not. Thus, the first shift workers would be the E+ group and the third shift workers would be the E- group. Both groups are then followed through time, and at a specified point in time (the CCD), everyone is assessed for D status.
The disadvantages of prospective f/up studies are that they typically require the investigator to wait a long time for the disease to occur, if the induction period for the disease is long, and "time is money.” A good cohort study will cost you millions of $$ and often take 10 – 15 years to produce meaningful results. Prospective f-up study can use p-years which permits a reduction in the number of study subjects, though, while increasing the number of years of exposure.
Retrospective F/Up Study
Epidemiologist starts at CCD (or present)
Groups still based on exposure status
Looking back to time zero to determine E status
Some are D+, some are D-
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A retrospective follow-up study still selects subjects based on exposure status, but the difference between it and a prospective f/up study is where the epidemiologist is in the study. Everything that is going to happen has already happened. For example, 10 years ago there was a chemical spill in a factory. The first shift workers were exposed, but the third shift workers were not. I decide to contact all of the first shift workers (E+) and third shift workers (E-) to determine D status.
Retrospective F-ups are the second most common study design. They don’t take as long as prospective cohort studies and can be done quickly. This is an especially good design for diseases with long induction periods and especially useful in occupational studies where they have good records on exposure status. However, they also have some pretty significant methodological issues which affects validity.. Retrospective studies require "historical" measurement (or inferences) about exposure at time-zero: Was each individual E+ or E-? Remember for an exposure to cause a disease, the exposure must occur first. If E+, what was the "dose" of E? (This is an example of information bias and is a factor that affects validity).
Another major disadvantage of retrospective f/up studies is that they are prone to confounding (which we’ll learn about in a future lesson) for several reasons. First, there is the prospect that what you think caused the death/illness of a cohort is in fact only a marker for some other cause. Secondly, there is a tendency toward observational bias because the researcher is often working with medical records containing historical information, with little likelihood of confirmation; the decision to exclude or include medical record is based on observer interpretation, and this may vary form on observer to another. Additionally, provider data may also be highly subjective (strong emotions are often involved in recalling the circumstances of illness or death).
| Prospective | Retrospective | |
| Costs (time and $) | --- | +- |
| Control of bias & confounding | +++ | - |
| Attrition/Loss to follow up | - | + |
| Clear E/D temporal sequence | + | - |
| Rare diseases | - | -+ |
| Rare exposures | ++ | +- |
| Multiple D outcomes | + | ++ |
| Allows estimation of AR | + | - |
Prospective vs Retrospective F-up Studies
Here’s a handy summary table that can help you be able to compare and contrast the pros and cons of prospective and retrospective f-up studies.
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Determining Exposure Status
Preexisting records
Medical Records
Study Subjects
Surrogate for study subject
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Another central issues in a follow-up study concerns the basis on which a given individual should be considered exposed.
The problem here is that there is no way to know whether or not they were, perhaps, exposed at a lower level. For example, let's say we want to look at the relationship between smoking and cancer. E+ are those who smoke and E- are those who don't. Seems fairly clear, right? Well, what about those E- who smoked in the past but are now non-smokers? What about those E- who are exposed regularly to second-hand smoke?
When determining exposure status, epidemiologists can use medical records and/or other preexisting records. Advantages include low cost and availability; disadvantages include potential for bias, no or limited information on confounders, and lack of details. Other sources for determining exposure status include interviewing or surveying study subjects (or their surrogates)
Analysis: F/Up Studies
Incidence rate of disease among the exposed compared to incidence rate of disease among unexposed
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F-up studies are analyzed by using RR, which you already know how to do: The incidence of D in the exposed group is divided by the incidence of D in the unexposed (i.e., if smokers develop 80 lung cancers per 1000, and nonsmokers only 5 per 1000, then the RR = 80 divided by 5 = 16; smokers were 16 times more likely to develop lung cancer).
Example:
To determine the relationship between oral contraceptive (OC) use and myocardial infarction (MI), a total of 3276 pre-menopausal female nurses were followed for a fixed period of time. Among those who did not use OC (n=2949), 133 had an MI by the CCD as compared to 23 of the 327 who used OC. What is the relative risk of having an MI with OC use?
Let’s walk through an example….
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1. Set up 2x2
| D+ | D- | total | |
| E+ | 23 | 327-23= 304 | 327 |
| E- | 133 | 2949-133 = 2816 | 2949 |
| total | 23+133 = 156 | 304+2816= 3118 | 3276 |
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Step 1: set up your data in the 2x2 table form (epidemiological matrix).
To determine the relationship between oral contraceptive (OC) use and myocardial infarction (MI), a total of 3276 pre-menopausal female nurses were followed for a fixed period of time. Among those who did not use OC (n=2949), 133 had an MI by the CCD as compared to 23 of the 327 who used OC. What is the relative risk of having an MI with OC use
2. Calculate RR
RR = incidence in E+/incidence in E-
Where IE+ = a/(a+b) and
Where IE- = c/(c+d)
RR = [23/(23+304)] / [133/(133+2816)]
= (23/237) / (133/2949)
=.07/.045
= 1.56
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RR = Incidence in the exposed divided by incidence in the unexposed, where IE+ = a/(a + b) and IE- = c/(c + d)
RR = [23/(23+304)] / [133/(133+2816)]
= (23/237) / (133/2949)
=.07/.045
= 1.56
Step 3: Interpret Results
The risk of myocardial infarction among OC users is 1.56 times as likely as the risk among those who do not use OCs (or 56% higher).
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This part should be review! =)
