Introduction - Uppsala Monitoring Centre

that I can find where the phrase ‘side effect’ is used was in 1891 (Stern, 1891).
Gradually the two words tended to be used together to describe an ADR as an
entity, e.g. side effect, and with continual use it became hyphened ‘side-effect’. This
term was used by Richard Doll in 1969 but since then it has, more or less, dropped
out of use except by the lay public (Doll, 1969). Other terms used have been ‘toxic
effect’, ‘side reaction’, ‘toxic reaction’, ‘toxic manifestation’ and ‘collateral effect’. The
use of the words ‘side’ and ‘collateral’ imply that the effect occurred at the normal
therapeutic dose and that it was intrinsic to the drug rather than dependant on
individual idiosyncrasy. It is now used by the lay public to refer to all adverse effects
of drugs whatever the dose.
In France in 1865 in a book on new medicines the phrase ‘accidents léger
périodiques’ was used (Guibert, 1865). Later ‘l’effets secondaire’ or ‘effet toxique’ or
‘effet latéral’ or ‘effet indésirable’ succeeded it (Bégaud, 1995). The Italians use the
phrases ‘effetto collaterale’, ‘eventi avversi da farmaci’ (ADE), ‘eventi indesiderati’
and ‘effetti secondari’.
Botanical nomenclature has always been a problem. A binomial nomenclature
was first mooted by Joseph Pitton de Tournefort (1656–1708), although it has been
claimed that Joachim Jung did so about 1640 (Morton,1970), but a superior system
was suggested by Carl von Linné, but known as Linnaeus (1707–1778) in his book
‘Systema naturae’ published in Leiden in 1735 (Taylor, 1979)
The typing of ADRs into type ‘A’ and type ‘B’ started in 1977 after a paper by
Rawlins and Thompson (Rawlins and Thompson, 1977). The term ‘adverse event’
was suggested for the collection of data in clinical trials in 1965 (Finney, 1965). The
phrase ‘adverse drug reaction’ dates back to 1957, but ‘drug reaction’ was used in
1934. Both the words ‘reaction’ and ‘effect’ imply certainty that something named
caused the reaction or effect. Doubt can only be expressed by adding an adjective,
e.g. possible, etc. The phrase ‘adverse drug event’ refers to an association between
drug and event, which is not necessarily causal and is therefore used prior to clinical
assessment of individual cases or statistical analysis in clinical trials.
Self-experimentation
The first known self-experimenter was Shen Nong in 2500 BC and it is likely that
there were many others after him before Storck. This process has continued at an
increased rate as more and more drugs become available, but in a more formalised
way as in phase I studies. It is common for students, clinical pharmacologists and
pharmaceutical industry personnel to volunteer for these self-experiments and
receive payment. Any ADRs may be exaggerated, as the volunteers would not have
the disease for which the drug was intended, e.g. postural hypotension with an antihypertensive.
The merit goes to those who took drugs for the first time as their
successors now knew the risks. There were three areas where there were many
self-experimenters: