It is Clinical Trials Awareness Day on 21st May and it is always good to reflect on the past and look to the future.
Humans have always experimented with medicines to treat ill health. In ancient Egypt, physicians prescribed figs, dates and castor oil as laxatives and used tannic acid to treat burns. In ancient China and Greece treatments included opium for pain relief. Hindus used cannabis and henbaneas anesthetics.
A school of pharmacy flourished in Arabia from 750 AD to 1258 AD. Among its many discoveries was the use of iodine, derived from burnt sponge, for the treatment of goitre. In Europe in the early Middle Ages much medical knowledge was based on Roman and Greek texts held in monasteries. It was believed that the causes of diseases could be attributed to sin, fate and astral influences.
During the European Renaissance period of 1400 -1700 there was a revival of the knowledge developed in ancient Rome and Greece. Arabic medical texts were translated and a more scientific approach to medicine began to evolve. Apothecaries (pharmacists) began to flourish. Although some of the new treatments were effective such as the discovery of quinine for the treatment of malaria, many medicines were ineffective as their use was often based on folklore and superstition. At this time there were no standardized and robust processes for the evaluation of medicines, so if being taken ill was bad enough, the treatment could be just as damaging to a person’s health.
However, scientific methodology was being applied in some isolated cases and what is considered to be the first randomized clinical trial took place on board HMS Salisbury in 1747. The ship’s surgeon, Lieutenant James Lind, conducted several experiments to test the effectiveness of citrus fruits (mainly limes) as a cure for scurvy.
Edward Jenner, an English physician, used folk knowledge to find a treatment to prevent smallpox infection. Recognizing that dairymaids infected with cowpox were immune to smallpox, Jenner deliberately infected James Phipps, an eight year old boy, with cowpox in 1796. He then exposed Phipps to smallpox which he failed to contract. After repeating the experiment on other children, including his own son, Jenner concluded that vaccination provided immunity to smallpox. Jenner’s findings were published in 1798. This research although valuable, fell way below the ethical standards we have today!
During the 19th century there were still no regulations of medicines and claims could be made without any scrutiny of scientific evidence. Even the availability of dangerous compounds was widespread and treatments could be bought over the counter from grocers’ shops and pharmacists.
At the beginning of the 20th century a more scientific approach to medicine was being adopted and controlled animal experiments were used to carry out medical research. With advances in chemistry the synthesis of ever more complex drugs was possible. More treatments became available for patients with the production of insulin in the 1920s and the discovery of penicillin in 1928, the latter leading to the search for further anti-bacterial agents.
The first trial using properly randomized treatment and control groups was carried out in 1948 by the Medical Research Council in the UK and involved the use of streptomycin to treat pulmonary tuberculosis. This trial also featured blind assessment enabling unbiased analysis of the results.
The thalidomide tragedy of the early 1960s saw the advent of much tougher regulations on the testing and licensing of drugs. More recently the Northwick Park incident in 2006, in which several clinical trial subjects suffered severe and serious side effects, caused a re-evaluation in the way that some treatments are tested and used in early studies in humans.
While much of the past focus of regulations has been on the process and procedures of the conduct of trials, the sector is now beginning to realize that human factors are also vital and that the competence of the people actually running the studies is vitally important. Clinical research continues to evolve as trials become more complex; diagnostic tools are becoming more precise, and advances in technology and artificial intelligence have a growing impact. The result is that individuals’ years of experience are becoming increasingly irrelevant. At IAOCR we believe that a robust assessment of competence is the way forward so that we can continue to celebrate International Clinical Trials Awareness Day with increasing confidence that patients are being protected and that clinical trial data is valid and verifiable.