Introduction - Uppsala Monitoring Centre

have and have not had an exposure to a drug. The two cohorts are then
compared
3 a. Prospective cohort studies
It was in 1662 that Helmont suggested that two cohorts of 200 or 500
patients with fevers, pleurisy, etc. should be used to compare treatments;
his patients, without bloodletting or purging with those of another physician
treated according to his custom and they would see who would have the
most funerals. Unfortunately the trial was never carried out.
In the next two centuries several prospective cohort studies were performed:
1. 1722 Nettleton compared patients inoculated against smallpox v
uninoculated. He inoculated 60 of his patients, and the controls were 3,405
cases collected from surrounding towns.
2. 1760 In Geneva 12 patients were treated for syphilis with mercurial
ointment v 12 patients treated with Keyser pills. The method of choosing
patients was not given.
3.1768 Watson pre-treated children before inoculation for smallpox with
mercury or senna plus rose syrup or untreated. Largest cohort 11. There
were no details of how he allocated treatment.
4. 1809 Army surgeon, Hamilton compared results of treating the 61st
regiment v 42nd regiment - bloodletting v no bloodletting. Alternative patients
chosen.
5. 1835 The Nuremberg salt test. Distilled snow water v homeopathic salt
solution. 54 participants had an equal chance of being in either the control or
experimental group.
6. 1898 Fibiger treated patients with diphtheria with standard treatment or
standard treatment plus serum treatment. Patients chosen according to their
day of hospital admission
The method of choosing the control patients is vital and the use of choosing
alternate patients continued until the 1948 Streptomycin trial. The methods
chosen in these studies were not ideal because of the possibility of selection
bias and information bias.
3 b. Retrospective cohort studies
Originally when physicians treated a series of patients with a new drug they
would have put the results into context by reference to their past experience.
Later they would have compared the results with the records of a previous
group of patients treated by other means but documented in the same way,
e.g. 1948 Colebrook’s study used this method but he realised that comparing
treatment with Sulphonamide and treatments used in the previous year for
Haemolytic streptococcal infections might be confounded by the possibility
that the virulence of the streptococcus might have declined in the interim, so
for the later studies he used concurrent controls allocating treatment in