As you’ve probably (hopefully!) picked up from other posts on this blog, my research is centred around clinical trials and their methodology. Trials can be intimidating for people that don’t know a whole lot about them, and as I’ve mentioned before, the ‘guinea pig‘ concept seems to haunt trial participation.
In this series of posts I want to answer any questions people have – from the basic to the obscure and everything in between – and demystify clinical trials. I asked a few friends who don’t work in a trials environment what they don’t know about trials, and the obvious starting point was ‘when was the first clinical trial?’, so here we are. Read on to find out when and how and first clinical trial came about.
Some sources say the first clinical trial was conducted in 605-562 BC, as outlined in the Old Testament’s Book of Daniel. Put simply, King Nebuchagnezzar II ordered the children of royal blood to eat only meat and wine for 10 days. Daniel asked that he and three other children be allowed only to eat vegetables, bread and water. After the 10 days was over, Daniel and the three children were noticeably healthier than the children who had eaten only meat and wine. Whilst this is clearly research (though as Ben Goldacre points out, probably underpowered research), the groups were not controlled. This was probably one of the first times in evolution of human species that an open uncontrolled human experiment guided a decision about public health.
James Lind is credited with the first controlled clinical trial; controlled meaning that his study included a comparison, or control, group. The comparison group received a placebo, another treatment or no treatment at all. Lind, a Scottish Naval Surgeon, conducted the first controlled clinical trial on the 20th May 1747 on a group of sailors suffering from scurvy.
He included 6 pairs of sailors in his trial; placed them all on the same diet, and then gave each of the pairs an additional intervention. One pair had a quart of cider each day; one pair took 25 drops of elixir vitriol (sulphuric acid) three times a day; one pair had 2 spoonfuls of vinegar three times a day; one pair were put on what Lind describes as a ‘course of sea-water’; one pair each had 2 oranges and 1 lemon given to them each day; and another had what’s described as a ‘bigness of a nutmeg’ three times a day.
I know which of the treatments I have preferred at that time (i.e. not a course of seawater!).
At the end of day 6 of Lind’s trial, the pair that had eaten 2 oranges and 1 lemon each day were fit for duty and taking care of the other 5 pairs of sailors. Lind notes in his book ‘Treatise on Scurvy’ (published in Edinburgh in 1753) that he thought after the citrus fruits, the cider had the best effects.
We now know scurvy is caused by a deficiency in vitamin C, hence why fruits rich in vitamin C had his sailors fighting fit again after just 6 days.
Clinical trials like James Lind’s are what we base our current practice on. Over the years since Lind found the cure for scurvy, huge advances have been made in the methodology of trials; we now have placebos, use randomisation, adhere to various codes of conduct, and work with huge groups of patients and teams of research staff across the world in an effort to answer clinical questions.
This is the first post in a series I’m calling ‘Clinical Trials Q&A’. If you have any questions about clinical trials, what they are, why we do them, what their limitations are.. etc, please pop them in a comment or tweet me @heidirgardner and I’ll be sure to answer them in upcoming blog posts.