The term 'epidemiologic triad' is used to describe the intersection of Host, Agent, and Environment in analyzing

an outbreak.[citation needed]

Case series
[edit]

Case-series may refer to the qualitative study of the experience of a single patient, or small group of patients
with a similar diagnosis, or to a statistical factor with the potential to produce illness with periods when they are
unexposed.[49]

The former type of study is purely descriptive and cannot be used to make inferences about the general
population of patients with that disease. These types of studies, in which an astute clinician identifies an
unusual feature of a disease or a patient's history, may lead to a formulation of a new hypothesis. Using the
data from the series, analytic studies could be done to investigate possible causal factors. These can include
case-control studies or prospective studies. A case-control study would involve matching comparable controls
without the disease to the cases in the series. A prospective study would involve following the case series over
time to evaluate the disease's natural history.[50]

The latter type, more formally described as self-controlled case-series studies, divide individual patient follow-
up time into exposed and unexposed periods and use fixed-effects Poisson regression processes to compare
the incidence rate of a given outcome between exposed and unexposed periods. This technique has been
extensively used in the study of adverse reactions to vaccination and has been shown in some circumstances
to provide statistical power comparable to that available in cohort studies.[citation needed]

Case-control studies
[edit]

Case-control studies select subjects based on their disease status. It is a retrospective study. A group of
individuals that are disease positive (the "case" group) is compared with a group of disease negative
individuals (the "control" group). The control group should ideally come from the same population that gave rise
to the cases. The case-control study looks back through time at potential exposures that both groups (cases
and controls) may have encountered. A 2×2 table is constructed, displaying exposed cases (A), exposed
controls (B), unexposed cases (C) and unexposed controls (D). The statistic generated to measure association
is the odds ratio (OR), which is the ratio of the odds of exposure in the cases (A/C) to the odds of exposure in
the controls (B/D), i.e. OR = (AD/BC).[citation needed]

Case
Controls
s

Exposed A B

Unexposed C D

If the OR is significantly greater than 1, then the conclusion is "those with the disease are more likely to have
been exposed", whereas if it is close to 1 then the exposure and disease are not likely associated. If the OR is
far less than one, then this suggests that the exposure is a protective factor in the causation of the disease.
Case-control studies are usually faster and more cost-effective than cohort studies but are sensitive to bias
(such as recall bias and selection bias). The main challenge is to identify the appropriate control group; the
distribution of exposure among the control group should be representative of the distribution in the population
that gave rise to the cases. This can be achieved by drawing a random sample from the original population at
risk. This has as a consequence that the control group can contain people with the disease under study when
the disease has a high attack rate in a population.[citation needed]
A major drawback for case control studies is that, in order to be considered to be statistically significant, the
minimum number of cases required at the 95% confidence interval is related to the odds ratio by the equation:

where N is the ratio of cases to controls. As the odds ratio approaches 1, the number of cases required for
statistical significance grows towards infinity; rendering case-control studies all but useless for low odds
ratios. For instance, for an odds ratio of 1.5 and cases = controls, the table shown above would look like
this:

Case
Controls
s

Exposed 103 84

Unexposed 84 103

For an odds ratio of 1.1:

Case
Controls
s

Exposed 1732 1652

Unexposed 1652 1732

Cohort studies
[edit]

Cohort studies select subjects based on their exposure status. The study subjects should be at risk of the
outcome under investigation at the beginning of the cohort study; this usually means that they should be
disease free when the cohort study starts. The cohort is followed through time to assess their later
outcome status. An example of a cohort study would be the investigation of a cohort of smokers and non-
smokers over time to estimate the incidence of lung cancer. The same 2×2 table is constructed as with the
case control study. However, the point estimate generated is the relative risk (RR), which is the probability
of disease for a person in the exposed group, Pe = A / (A + B) over the probability of disease for a person
in the unexposed group, Pu = C / (C + D), i.e. RR = Pe / Pu.

..... Case Non-case Total

Exposed A B (A + B)

Unexposed C D (C + D)

As with the OR, a RR greater than 1 shows association, where the conclusion can be read "those with the
exposure were more likely to develop the disease."
Prospective studies have many benefits over case control studies. The RR is a more powerful effect
measure than the OR, as the OR is just an estimation of the RR, since true incidence cannot be calculated
in a case control study where subjects are selected based on disease status. Temporality can be
established in a prospective study, and confounders are more easily controlled for. However, they are
more costly, and there is a greater chance of losing subjects to follow-up based on the long time period
over which the cohort is followed.