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Clinical Epidemiology:
A Multi-level Research Problem
To round off this week, let’s look at an example of a common clinical problem that’s been addressed at
several levels by clinical epidemiological research.

Acute otitis media, commonly known as middle ear infection is a common disease, especially in young
children. Roughly 80% of all children in developed countries have at least one episode of acute otitis
media during their infancy. In fact, for children it’s a leading cause of visits to primary care, and as a
result creates a large burden for health care systems. Worldwide, pain medication is the mainstay of
treatment of otitis media. In addition, antibiotics are widely prescribed for this condition, even though
this remains highly controversial in view of the limited beneficial effects of antibiotics, as evidenced by
available trials, and the potential side effects, such as diarrhea and antibiotic resistance.

To help us get a clearer picture of where the clinical challenges lie, let’s think about a typical situation
we might see in practice. A parent brings their child into the clinic, explaining that he’s had an earache
since yesterday. Your patient is 18 months old, with no history of acute otitis media. He has a raised
temperature, and seems quite agitated. You perform a basic examination and find that there’s bilateral
inflammation of the ear drum. Reaching a diagnosis of bilateral acute otitis media seems
straightforward, but there are certainly other clinical challenges. Should you simply prescribe antibiotics
and be done with it? Or should you consider more carefully the characteristics of your patient’s disease
and whether the inflammation will resolve quickly on its own with some rest? Without clear evidence,
it’s difficult to know what the best decision for your patient will be.

As you can see, there are several intertwining clinical problems in front of us. In order to begin
addressing these issues through research, we first need to untangle the individual problems and identify
in which clinical research areas the problems lie. We can refer to our DEPTh model as a guide.

The first branch we should consider is diagnosis. While the accurate diagnosis of acute otitis media is
important for proper patient management, the signs and symptoms are well established and it’s usually
straightforward. Our problems lie elsewhere in the model.

What about the etiology of disease? Is there an issue here? Otitis media is a general term for a group of
diseases related to inflammation of the middle ear. It may be that there’s a specific causal agent behind
our patient’s current bout of disease. Though the causal agents of otitis media have been known for a
long time, an etiologic study would have once been informative in addressing this question. Acute otitis
media is usually caused by a virus, but also several kinds of bacteria may cause the disease. While
etiology isn’t usually directly important in clinical decision making, in this case, it certainly has
implications regarding a patient’s prognosis and therapy, because bacterial infections may have a poorer
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prognosis and antibiotics won’t work when the otitis is caused by a virus. And that brings us to the next
aspect of our clinical problem.

When you first diagnose a child with acute otitis media, one of the first questions you might find
yourself asking is, what’s the most likely course of this patient’s disease? How severe is it likely to
become and for how long will the symptoms continue if left alone. We’re now faced with a challenge in
prognostication. If a child is more likely to go on to have a longer or more severe case of acute otitis
media, you may want to recommend certain intervention measures for that child, such as treatment
with antibiotics; whereas if a child’s symptoms are likely to clear up in a day or two, you’d probably
reconsider prescribing antibiotics and only prescribe pain medication.

So how can we distinguish between patients with a benign course and a more prolonged course of their
otitis media? Well, on the face of it, it isn’t always especially clear. It’s this difficulty that has potentially
led to a huge level of over-prescription of antibiotics to children. To solve this problem, we need more
evidence, and to acquire this evidence we need to conduct a prognostic study. Such a study could help
us to identify which characteristics of our patients and their disease manifestations indicate an
increased risk of a more severe course of disease.

Prognostic studies have shown that you can in fact distinguish between children who are more or less
likely to go on to have a longer course of disease. In these studies children with confirmed acute otitis
media were monitored over time, and general information such as their age, as well as information
about the features of their otitis media were recorded. It turns out that children who are under two
years old with bilateral acute otitis media are more likely to have a longer disease duration.

Does this mean that we should only prescribe antibiotics in this patient subgroup, or are they still
effective in other subgroups? Are they even effective at all? With these questions we find ourselves at
the final branch of the DEPTh model, in therapeutic, or intervention research.

To investigate these research questions, we need to conduct an intervention study. If the effectiveness
of antibiotic treatment is really in question, we could consider setting up a study where patients are
randomly assigned antibiotic treatment, or placebo, and followed to see how long their symptoms last.
We may want to assess the effect of treatment within subgroups, as suggested by the result of our
prognostic research, to see whether treatment is more effective in younger children with bilateral
inflammation. The evidence that we gather in order to address these questions may bring us closer a
resolution for our overall concern regarding the over-prescription of antibiotics in these children.

Once again, these studies have already been conducted, and a meta-analysis combining information
from a number of studies found that, in line with the results of prognostic research, the greatest benefit
from antibiotics is seen in children under two years of age with bilateral acute otitis media.

So what does this mean for our 18-month old patient? Well, as he’s both young and showed signs of
bilateral inflammation, it’s likely that he‘ll have a longer, more severe course of disease if left untreated.
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It’s also likely that treatment with antibiotics will reduce the duration of his symptoms, and therefore in
this case we could decide to prescribe a course of antibiotics. As for all interventions, this decision
should be made taking the patient’s, or in this case his mother’s, preferences into account.

There are several messages to take away from this example. Firstly, we’ve seen that clinical problems
are often complex, and several kinds of research may be required to address an overall problem. We’ve
also seen that such research can effectively solve these problems if conducted properly, with the right
questions and goals in mind. Finally, we‘ve seen that the results of clinical epidemiological research can
be directly applied in practice to aid in problem solving and decision making for future patients.