Introduction - Uppsala Monitoring Centre

clinical trial (4).
1. Case reports
These are reports of single patients, which may produce hypotheses; but
rarely give sufficient information to be able to exclude alternative causes.
However on rare occasions they can show that a drug did cause the event
in that particular patient, e.g. a well-documented positive rechallenge, but
even these can be misleading (Stephens, 1983). They can give no idea of the
frequency of the reaction, e.g. In 1061 two patients ran a race one having had
ginseng and the other not. At the end of the race their shortness of breath was
compared. The is the earliest comparison of two treatments that I have found
and it would have been insufficient to draw conclusions, which could have
been extrapolated to other patients.
Horace in 23 BC said that after taking Hellebore ‘I’ve lost the pleasure of
imagination’, but gives no information as to how he drew this conclusion. Later
in 1530 Paracelsus reported the cases of individual patients whom he had
treated with mercury for persistent syphilis and came to the conclusion that
he had cured all the patients. His claims are not credible. Self-experimenters
often produced stronger evidence by taking a drug and then taking objective
measures subsequently, e.g. Samuel Crumpe in 1793 with opium. Single case
reports, especially as part of spontaneous reporting to regulatory bodies, have
been one of the most successful means of creating hypotheses (Venning
IV,1983), but these have rarely been validated (Loke et al., 2006).
2. Case series
These concern patients who have been exposed to a drug and the adverse
events that they have suffered have been reported by the prescriber. They can
give some idea of frequency. Again they rarely have sufficient information to
be able to exclude alternative causes. Since neither a case report nor a case
series have a control group other than historic controls they cannot exclude
bias, e.g. when Xenophon in 354 BC said that hyoscyamus drives those who
take it mad he was, no doubt, referring to his experience of what had
happened to the patients he had treated. An excellent example of a case
series was that performed by Samuel Bard in 1765 using opium and making
regular recordings of the pulse. He repeated the experiment on himself three
times giving a double positive rechallenge. Most of the publications mentioned
in this book must have been based on case series of the authors, perhaps with
evidence from previous authors. Case series have discovered most of new
important ADRs described in this book, e.g. thalidomide, streptomycin and
Aspirin.
3. Cohort studies
These are prospective or retrospective studies of groups of patients who