Introduction - Uppsala Monitoring Centre

0.7% of patients received a prescription violating a black box warning (Lasser et al.,
2006).
Restrictions on dose and dosage forms. Restrictions on prescriptions, i.e. overthe-counter
v prescription only
Demand monitoring of all patients, e.g. penicillamine and urine testing; clozapine
and neutropenia.
Restrict the type of patients who can be prescribed the drug, e.g. Aspirin and
Reyes’s syndrome; thalidomide and pregnancy
Restriction to named patients (tiabendazole and strongyloidiasis)
The process of subjectively estimating whether the possible outcomes are
favourable or unfavourable, weight these by the probability that each outcome will
occur and intuitively choose the option with the heaviest weighted score. This is
known as ‘subjective expected utility theory’. This is the application of logic to a
problem, but this is only part of the decision process.
There remains the illogical approach, which probably always plays a part.
There are many unethical factors, which come into play:
Political corruption
Pressure from the pharmaceutical industry.
Pressure from patient groups, which are frequently financed by the
pharmaceutical industry.
There are also well known cognitive biases, which are likely to influence decision
making (Greenhalgh et al., 2004).
An example of a drug with important ADRs that was allowed to stay on
the market
In 1928 Sedormid, allyl-isopropyl-acetyl carbamide (urea), was marketed in
Germany by Hoffman-La Roche as a hypnotic, and was first shown to cause
thrombocytopenic haemorrhagic purpura in 1931. The first paper published on this
ADR was in 1934 (Loewy, 1934), but it wasn’t until after July 1938 that it was
mentioned on the packet (Loewy, 1938). It had been said in 1936 that ‘There was no
reason for prescribing drug with this alarming potentiality,’ but elsewhere that it was
‘practically non-toxic’. In 1958 it was said to be ‘almost completely discontinued’ and
in 1963 it was said to be ‘too toxic for general use’. (Leader, 1963). Hoffman-La
Roche introduced Librium in 1960 and probably lost interest in marketing Sedormid.
By 1969 Sedormid was ‘no longer available’. It was last sold in Mexico in 1975
(Roche, 2009). In 1992 BIAM said that the ADR was ‘certain, very rare’. From 1993
until 2006 a few cases of fixed drug eruption were published in the Japanese press
indicating that it was still available. In 2003 there were 57 OTC drugs containing the
drug on sale in Japan. It is strange that several Japanese companies started
incorporating Sedormid in analgesic tablets with such analgesic drugs as
paracetamol, Phenacetin, isopropylantipyrine and ibuprofen from about 1992. It is