Chatu Yapa, Masters in Applied Epidemiology trainee

## Problem 1: The R value

At present, the countries of Guinea, Sierra Leone and Liberia in West Africa are experiencing the largest outbreak of Ebola virus disease (EVD) that has occurred in history. While efforts are being made to implement public health measures in the affected regions, each week there is an upward trend in the number of newly confirmed cases and deaths from the disease.

In an epidemic such as that occurring in West Africa, epidemiologists can measure the spread of infection by calculating a number called the basic reproduction number, also called R0. The basic reproduction number is defined as the number of secondary infections generated by an infected index case in the absence of control interventions in a population that is completely susceptible to the disease.

R0 is used to measure the transmission potential of a disease, and for an epidemic to occur in a susceptible population, the value of R0 must be greater than 1.

The basic reproductive number has been calculated for the current EVD epidemic using mathematical models [1] and is estimated to be at 2. This means that every infectious case has the potential to produce 2 new secondary cases. The diagram below compares the R0 for EVD and for other more well-known diseases such as measles and HIV (in a completely susceptible population) [2].

### Questions

1. What value must R0 be, for an epidemic to stop?
2. What factors might affect the basic reproduction number?
3. What measures can be taken to reduce R0?

## Problem 2: Some aspects of case control studies

A case-control study is a useful epidemiological study type that tries to determine whether an exposure is associated with an outcome. In theory, the case-control study can be described simply. It requires that cases are identified - a group known to have the outcome - as well as controls - a group known to be free of the outcome. Researchers can then look back in time to find out which subjects in each group had the exposure(s) and compare the frequency of the exposure in the case group to the control group.

Here we discuss a case-control study made famous for all the wrong reasons.

In 1981, an eminent Harvard professor of epidemiology published a paper in the New England Journal of Medicine investigating the association between drinking coffee and the occurrence of pancreatic cancer. The conclusions of the study were that there was a ‘strong association between coffee consumption and pancreatic cancer’. They found that the risk associated with drinking up to two cups of coffee per day was 1.8, and that with three or more cups per day, the risk was 2.7.

In conducting the study, the researches enrolled cases with histologically confirmed pancreatic cancer from 11 large hospitals in the Boston and Rhode Island area over a 5 year time period. The controls were patients who were under the care of the same physician in the same hospital at the time of an interview with a patient with pancreatic cancer.

The idea was to make the process of selecting the cases and control as similar as possible.

However, what the study group failed to understand at the time of recruitment, was that patients often seen by physicians who treated pancreatic cancer were those with other gastrointestinal disorders. These ‘control’ patients were often advised not to drink coffee or had chosen to reduce coffee drinking on their own accord. This in turn, led to the selection of controls with a higher prevalence of gastrointestinal disorders who had unusually low odds of exposure, that is, intake of coffee.

The results of this study could not be reproduced by other researchers and led to some questioning of the study methods.

### Questions

1. In this study, what is the term given to the form of bias that is evident in the recruitment of controls?
2. How might choosing controls with lower odds of exposure affect the strength of association between the exposure and outcome?
3. What are the advantages and disadvantages of conducting a case-control study for a study like this?