Introduction - Uppsala Monitoring Centre

and nialamide; biguanides, e.g. buformin and phenformin.
15. Chronicity of ADR: e.g. Phenacetin where the study started in 1968 and the
result published in 1991 (Dubach et al., 1991); 38 years after the hypothesis
was first mooted.
16. Under reporting of ADRs: prior to 1960 there were no centres for the reception
of suspected ADRs?
17. Even the most advanced countries, from the regulatory point of view, were
hampered by insufficient regulations, inadequate science, absence of databases
and few experts. ‘Before 1938 it would be difficult to say that drug development
had any plan or requirements at all, although certainly some effective
agents emerged and some facts about them were discovered. But
there were few of the drugs we now consider effective and there were real
disasters.’ (Temple, 1996).
18. Variation in the incidence of the ADR due to poorly known factors, e.g. analgesic
nephropathy was greater in Glasgow perhaps because most of the
factories making Phenacetin were sited there. Similarly in Belgium, most
cases were found in the county of Antwerp where the factories were sited.
The incidence varied considerably from country to country: Australia 20%,
Belgium 18.4%, Switzerland 17.5%, USA 7-10%, Germany 5%, Scandinavia
3.4%, Canada 2.5% France 1.6%, UK 1.2% Italy 1.0% (Vanherweghem &
Even–Adin, 1982).
19. Although only one ADR might be named as the reason for withdrawal of a
drug from the market the regulatory authorities would also have been influenced
by the other ADRs attributed to the drug.
20. Date when the drug was introduced. Over the time span of this book there
have been many changes in the attitude of patients and regulators towards
the adverse effects of drugs. It is only post 1960 that research into why
drugs are withdrawn from the market has been undertaken.
Information concerning the reasons(s) why a drug has been removed from a
specific market are difficult to obtain, e.g. Health Canada did not maintain a
comprehensive list of drugs that had been removed from Canada because
of safety concerns, nor did it have a database that would allow the construction
of such a list. For sixteen out of the 41 products removed from the Canadian
market between 1963 and 2004 there was no definite information
about why they were removed from the Canadian market, although they
were withdrawn in either the UK or the US (or both) because of safety concerns
(Lexchin, 2005).