Introduction - Uppsala Monitoring Centre

The classical study of Sulphonamide for the treatment of puerperal
fever by the Therapeutics Trials Committee of the MRC in 1937
included 106 patients with fever and a positive culture of haemolytic
streptococcus Group A. They used historical controls from the same
hospital and under the same physician, who had been treated with
‘Red Prontosil’ and ‘Prontosil Soluble’ in the previous year (1936)
and patients from the years 1931–35, who had mostly received no
treatment. The death rate in this study was 8% compared with 22.8%
in the controls (1931–1935) and 4.7% in the controls treated with the
Prontosils. Under toxic effects:
Drug fever: it was difficult to differentiate between the disease and
drug effects.
Cyanosis with met- or sulph-haemoglobin–more than 50% (58
patients)
Nervous system: depression, headache, dizziness, blurred vision,
‘spots before the eyes’ and parathesia of peripheral nerves have
occasionally been observed
Mental disturbances: hysterical type–two
Joint pains: in a few cases
Transient skin eruptions: also seen occasionally
Jaundice: slight in two patients
Urine: two cases with casts and three with albuminuria (Colebrook
& Purdie, 1937).
Perhaps the dramatic saving of life with the sulphonamide
compared with no treatment overshadowed concerns for minor
adverse effects, but is characteristic of this period that little was done
to investigate and enumerate ADRs.
The Swedish authorities published the Lex Maria, which assigned
the duty of a local authority to notify the National Board of Health and
Welfare (NBHW) and the police of every serious patient injury or the
risk of serious injury caused by medical treatment. This was
precipitated by the deaths of four patients in the previous year, who
had been given mercuric oxycyanide instead of a local anaesthetic at
the Maria hospital Stockholm (Ödergård & Löfroth, 1991).
1938 Another study of a sulphonamide, this time M&B 693 168 , in the
treatment of pneumonia used as controls patients admitted under
other physicians receiving the usual standard treatment. These two
168 M&B 393 = The new chemical 693, a sulphonamide, sulfapyridine,, discovered by May and Baker
laboratories