Introduction - Uppsala Monitoring Centre

any adverse effects and therapeutic results observed.
Many of the cases reported in the application are in summary form
without the necessary details included. In addition, the application is
inadequate under section 505 (b) (1) of the act in that insufficient
cases have been studied. Many of the 3,156 cited cases are in
foreign literature reports and in many instances the reports do not
represent detailed studies to determine the safety of the drug. The
application should contain more cases in which detailed studies have
been done.
The application is further inadequate and incomplete under section
506 (b) (1) of the act in that the chronic toxicity data are incomplete
and therefore, no evaluation can be made of the safety of the drug
when used for a prolonged period of time.’ (Sjöstrom and Nilsson,
1972).
1961 December 16th 1961 Dr WG Mc Bride’s letter was published in the
Lancet announcing his observation ‘that the incidence of multiple
severe abnormalities in babies delivered of women who were given
the drug thalidomide (‘Distaval’) during pregnancy as an anti-emetic
or as a sedative, to be almost 20%.’ The Distiller’s Company in
Liverpool had received the news on November 21st 1961. Dr
Widukind Lenz from Germany saw a suspected case for the first time
on November 11th 1961 and informed the company on November
16th 1961. This changed the whole world of drug safety.
Dr Mcbride was discredited 20 years later in the Benedectin case
when he stated the Benedectin ‘is not safe and that it caused birth
defects’. Bendectin - A combined preparation of doxylamine,
dicyclomine and pyridoxine was marketed in the US for nausea of
pregnancy under the name of Bendectin and in the UK two years
later as Debendox. The long shadow of thalidomide claimed it as a
victim when it was alleged to cause congenital abnormalities. Nine
cohort studies and case-control studies failed to show a causal
relationship, but in spite of this the drug had to be withdrawn from the
market in 1983 (MacMahon, 1981; Orme, 1985). Finally a legal
action found for the company and no damages were ever awarded to
the 1100 plaintiffs (Masheter, 1985).
The plaintiff’s case was that there was a relative risk of 1.49 and
confidence limits of 0.17 to 3. They did not offer a single study that
did not include a confidence interval including 1.0 (Christoffel &
Teret, 1991). Another assessment of these studies showed a relative
risk of 0.89 with confidence intervals of 0.76 to 1.04 (MacMahon,