The term ‘Signal Recognition’ arises from electronic engineering, where with radio or radar waves there is a real signal that exists but it is accompanied by ‘noise’ in the background, and there is a need to detect the signal, distinguishing it from the background.
Statistical Methods
of Signal Detection
INTRODUCTION
The
term ‘Signal Recognition’ arises from electronic engineering, where with radio
or radar waves there is a real signal that exists but it is accompanied by
‘noise’ in the background, and there is a need to detect the signal,
distinguishing it from the background. This terminology has been used in other
contexts, notably in medical diagnosis where similarities to the prob-lems in
electronics can also be seen. The terminology of electronics has been continued
with ‘Receiver-Operating-Characteristic’ curves. These illustrate that with a
given amount of information there must always be a trade-off between the risk
of the two different errors of classification: calling noise a signal (a false
positive) and calling a true signal noise (a false negative). The sensitivity
of a diagnostic test is high when there is a low false negative rate; the
specificity of a diagnostic test is high when there is a low false positive
rate.
With
adverse drug reactions (ADRs) there are two levels of diagnosis of causality:
first, diagnosis at a single case level; secondly, at a public health or
epidemiological level. ADR causality in an individual patient is not the
subject of this chapter, but statistical approaches may help with single cases.
The public health and epidemiological perspective is of greatest importance,
and statistical methods can be of some help. The objective is to find those
signals that are indicative of causal effects, and to reject those signals of
effects that are not caused by a particular drug. Where they are of public
health significance they will either affect large numbers of individuals or
have extremely serious effects in smaller numbers. In these circumstances, the
public health view requires that true reactions caused by a medicine be
recognised as early as possible. At the same time, those suspected reactions
that are not caused by a medicine should be recognised as such and minimal
resource should be spent on investigating them.
Signals
of potential harmful effects may arise from literature reports, observational
epidemiological studies, randomised trials and spontaneous reports of suspected
ADRs. In some countries the emphasis is on suspected reactions but in others
the emphasis is on adverse events. This chapter will concentrate on the
analysis of large volumes of these spontaneous reports. Their source will
usually be health profession-als but may also include patients. The early
evidence from spontaneous reports can be regarded as a poten-tial ‘signal’.
This has been defined as showing a ‘possible causal relationship between an
adverse event and a drug. Unknown previously’ (Wood, Coulsen and Eccles, 1994).
The object is to distinguish the real signals from ‘noise’ precisely.
The
details of spontaneous reporting will not be covered here. The salient feature
is that health profes-sionals, particularly doctors, report suspected ADRs
centrally; this can be to a regulatory authority or to a company. These reports
are processed and entered on to a database. Whether they are reported as
suspected ADRs or as adverse events there will inevitably be some background
reports that are not caused by the drug. There will often be a very large
number of reports, and an essential task is to prioritise those that should be
investigated first. The purpose of collecting these reports is to detect
signals. Even in countries where reporting of ADRs is supposed to be
compulsory, reporting rates will usually be much less than 100%. A typical figure
is said to be 10%, but it depends very much on the seriousness and newness of
the ADR. In the case of fibrosing colonopathy caused by high-strength
pancreatic enzymes, the rate was shown to be 100%.
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