Today's clinical trials evolved from trial-by-error studies of new treatments.

Clinical trials are used to test new drugs and therapies on human volunteers. Today, such investigations are carried out using protocols that adhere to accepted standards of safety, patient care and data interpretation. However, history shows that patient welfare was not always such a high priority.

The earliest recorded clinical trial is documented in the Old Testament, and describes how Daniel followed a diet of pulses and water instead of the meat and wine recommended by King Nebuchadnezzar II. Daniel remained healthy while his companions became ill, convincing Nebuchadnezzar to change his mind.

The first clinical trial of a novel therapy was conducted unintentionally by the Renaissance surgeon Ambroise Parè in 1537. He used a concoction of turpentine, rose oil and egg yolk to prevent the infection of battlefield wounds, noting that the new treatment was much more effective that the traditional formula.

Preventing scurvy

Most people think of James Lind as the father of clinical trials, since he was the first to introduce control groups into his experiments. In this manner, he documented the fact that citrus fruits in the diet could prevent scurvy. Lind carried out trials while at sea on board the Salisbury in 1747. All scurvy patients were given the same general diet but this was supplemented with various additional items, including cider, elixir vitriol, vinegar, seawater, nutmeg and (crucially) oranges and lemons. In just six days, those patients taking citrus fruits were fit for duty.

Although the results were clear, Lind hesitated to recommend the use of oranges and lemons because they were too expensive. It was nearly 50 years before the Navy eventually made lemon juice a compulsory part of the seafarer's diet, and this was soon replaced by lime juice because it was cheaper. This is why British sailors, and later the British in general, were called 'limeys' by the Americans.

Modern clinical trials

From 1800 onwards, clinical trials began to proliferate and more attention was paid to study design. Placebos were first used in 1863, and the idea of randomisation was introduced in 1923.

The first trial using properly randomised treatment and control groups was carried out in 1948 by the Medical Research Council, and involved the use of streptomycin to treat pulmonary tuberculosis. This trial also featured blind assessment (where neither the researchers nor the patients knew which treatment group each patient was in at the time of the study) enabling unbiased analysis of the results.

Since 1945, the ethical impact of clinical trials has become increasingly important, resulting in strict regulation of medical experiments on human subjects. These regulations have been enshrined in documents such as the Nuremburg Codex (1947) and the Declaration of Helsinki (1964, amended in 1975, 1983, 1989, 1996, 2000 and 2001).

Clinical trials have thus evolved into a standard procedure, focusing on patient safety and requiring informed consent from all participants. There will always be a balance between medical progress and patient safety, and the regulation of clinical trials helps to ensure that this balance is acceptable.

Richard Twyman