Clinical trials are an integral part of our fight against blood cancer. They form a vital step in our research pipeline and facilitate the translation of basic science into new and improved standardised treatments for patients. Bloodwise has been investing in clinical trials for over a decade now and this support has directly facilitated a range of important advancements in the development of new drugs and therapies for blood cancer. This is the first of two blogs that will attempt to better understand where clinical trials have come from and how they have been used thoughout history. In this first blog I will focus on a few early examples...
Cast your mind back to roundabout 600 BC, in the ancient area of Mesopotamia (where the modern day country of Jordan now occupies). A good candidate for the world's first clinical trial was taking place which was later recorded in the “Book of Daniel” in The Bible . This experiment conducted by King Nebu of Babylon was the first to compare two forms of intervention and explicitly monitor the results. The King ordered his soldiers to 'eat only meat and drink only wine' in an effort to improve their battle readiness. A number of his soldiers disagreed and told the King they intended to eat a diet of mainly vegetables. The King allowed this alternate diet but restricted the test to 10 days before he would compare the results. At the end of the 10 days the King observed the soldiers who had eaten the legume and water based diet were in markedly better shape in comparison to the meat eaters. The King subsequently permitted the legume lovers to continue with their diet and used the lesson to diversify the diet of the whole army.
Fast forward around 2300 years, as you do, and James Lind (1716-94) is considered to be the first physician to have conducted a fully controlled clinical trial of the modern era. Dr Lind , whilst working as a surgeon on a ship, was very interested in the health of the sailors onboard and troubled by the high mortality of scurvy amongst the men. He planned a comparative trial of the most promising cures for scurvy at the time. His famous description of the experiment below covers the essential elements of a controlled trial..
“On the 20th of May 1747, I selected twelve patients in the scurvy, on board the Salisbury at sea. Their cases were as similar as I could have them. They all in general had putrid gums, the spots and lassitude, with weakness of the knees. They lay together in one place, being a proper apartment for the sick in the fore-hold; and had one diet common to all, viz. water gruel sweetened with sugar in the morning; fresh mutton-broth often times for dinner; at other times light puddings, boiled biscuit with sugar, etc., and for supper, barley and raisins, rice and currants, sago and wine or the like. Two were ordered each a quart of cyder a day. Two others took twenty-five drops of elixir vitriol three times a day … Two others took two spoonfuls of vinegar three times a day … Two of the worst patients were put on a course of sea-water … Two others had each two oranges and one lemon given them every day … The two remaining patients, took … an electary recommended by a hospital surgeon … The consequence was, that the most sudden and visible good effects were perceived from the use of oranges and lemons; one of those who had taken them, being at the end of six days fit for duty … The other was the best recovered of any in his condition; and … was appointed to attend the rest of the sick. Next to the oranges, I thought the cyder had the best effects …” (Dr James Lind's “Treatise on Scurvy” published in 1753)
It took another century before the next important discovery in the history of the modern clinical trial. The word placebo first appeared in Hooper's Medical Dictionary of 1811, which defined it as “an epithet given to any medicine more to please than benefit the patient.” However, it wasn't until 1863 that Austin Flint, a physician in the then United States, planned the first clinical study in patients suffering from rheumatism. He compared a dummy placebo remedy against a new herbal extract treatment and found the herbal based remedy to be preferable to placebo.
Fast forward again another 100 years and the UK Medical Research Council (MRC) carried out a trial in 1943 to investigate patulin treatment (an extract of Penicillium patulinum) for the common cold. This is widely recognised as the first double blind comparative trial with concurrent controls in the general population. This first patulin trial presided the first properly randomised control trial of streptomycin in pulmonary tuberculosis carried out in 1946 also by the MRC. This milestone trial was a model of attention to detail in design and delivery, with strict systematic enrolment criteria and data recording, compared with the less tightly controlled designs of other contemporary clinical research.
As we can see, clinical trials have come along way since King Nebu's time over two and half millenia ago, they are now a standardised investigative procedure, focusing on the scientific assessment of efficacy whilst always guarding patient safety.
Clinical trials will also continue to be a vital part of our battle with blood cancer and as novel technologies and practices are used in the development of new treatments, there will be a continuing need to ethically and efficiently gather clinical evidence to inform medical progress.
Keep an eye out for part two of this blog, in which I'll explore current clincal trial practice, TAP, research ethics and all the relevant EU/UK regulations.