For more than 275 years, clinical trials have been an integral component of medicine, giving doctors the chance to discover effective cures for a variety of diseases.

The Greek physician Hippocrates referred to as the father of medicine founded the Hippocratic School of Medicine. He created the medical field as a distinct profession and is credited with creating the ‘Hippocratic Oath’. By signing it, doctors and other healthcare workers pledge their commitment to reasonable and moral medical practice.

The first clinical studies were conducted around 500 BC. From nutritional therapy to medications, clinical research has advanced.

Before James Lind's time: 562 BC until 1537

The Bible's "Book of Daniel" (605 BC) has information about the very first clinical study ever conducted. One of the first times in the history of the human species where an open, uncontrolled human experiment served as the basis for a choice on public health. During the reign of Nebuchadnezzar (approximately 500BC), the Babylonian king ordered his people to follow a strict diet of just meat and wine, believing that this would keep them healthy. However, a few royally young men who wanted to eat vegetables opposed so the king permitted them to eat only lentils and water for 10 days. When the king's experiment concluded, the vegetarians seemed to be better fed than the meat eaters.

In 1537, Ambroise Pare was in charge of caring for the soldiers who had been injured on the battlefield. He had to use unorthodox treatment because there were many injured people and there wasn't enough standard medical oil to treat everyone. So, he was forced to use medicines composed of egg yolks, rose oil, and turpentine in place of oil. Those to whom he had administered the digestive medication reported little discomfort, no swelling or inflammation of their wounds, and a full night's sleep. This is a case of a clinical trial that was undertaken by mistake.

As a result, it took an additional 200 years to organize a planned controlled study.

James Lind and the Scurvy Trial, 1747

James Lind is renowned as being the first doctor in the contemporary period to undertake a carefully monitored clinical trial. He was amazed to find the high scurvy mortality rate among sailors while working as a surgeon on a ship. He envisioned comparing the most effective treatments for scurvy.

To find a technique to lower the high death rate linked with scurvy among sailors, he divided a group of scurvy patients into different groups and required each group to follow a particular regimen. He found that citrus fruits like oranges and lemons, which are high in vitamin C, had the best results during this investigation, leading him to design a technique to protect sailors against scurvy in the future.

Therefore, every year on May 20th, ‘Clinical Trials Day’ is observed to honour the day Dr. Lind started the trial.

1800: Placebo enters the scene

Another century passed until the development of the placebo, a crucial turning point in the development of modern clinical trials. A placebo is typically a pharmaceutically inert substance that is recommended more for the patient's mental comfort than for its actual impact on a problem

In a clinical trial frame, placebos are an effective tool that makes it simpler to estimate the true impact of a treatment. Beforehand in the nineteenth century, the expression first appeared, in the 1811 edition of Hooper's Medical Dictionary. 

Europe in the eighteenth century was a hive of exertion due to the frequent discoveries of enigmatic and unnoticeable powers. Newton established the reality of graveness. Electricity was captured and experimented with by Benjamin Franklin. Franz Anton Mesmer, an Austrian croaker, claimed to have set up another unnoticeable force in Vienna that can cure all physical affections. By applying attractions to his cases, he tried to cure them. There, word of Mesmer's treatments snappily spread, and the croaker soon had further cases than he could handle. When Mesmer gestured his hands over or touched the women, they would writhe, scream, and fall to the ground. He also treated 13 cases suffering from rheumatism with an herbal excerpt which was advised rather than an established remedy.

Two commissions were established by King Louis XIV (1782) to look into Mesmer's statements. Benjamin Franklin and Dr. Joseph- Ignace Guillotin chaired one commission, and members of the Royal Society of Medicine served on another. The results of the trials demonstrated that beast captivation was a myth, and its apparent goods were the result of people's faith in Mesmer's capacities. Franklin and his platoon so concluded that Mesmer's true strength began from his cases, who used the power of their studies to heal themselves. Since also, psychologists and hypnosis in the medical field have bettered that system, enabling cases to suffer an excruciating operation without being sedated. 

Founded in 1887: National Institute of Health (NIH)

Joseph J. Kinyoun established the National Institute of Health. Today, the National Institutes of Health (NIH) is the largest public supporter of biomedical research worldwide, spending billions yearly to improve health and reduce disease and disability.

Food and Drug Act of 1906

The FDA Pure Food and Drug Act, which prohibited the interstate transportation of illegal food and medications, was passed into law by President Theodore Roosevelt and stipulated that products could not be marketed for purposes other than those specified on their labels.

Patulin's first controlled trial for the common cold, 1943

A double-blind study is a randomized clinical trial in which neither the patient nor the doctor is aware of whether the patient is receiving the experimental treatment, a standard treatment, or a placebo.

The first double-blind clinical trial was carried out by the Medical Research Council (MRC) in the UK to find a cure for the common cold. Patulin, an extract of Penicillium platinum, was the target treatment, and it was provided under the tight supervision of the treating physician and patient. Even though the study itself did not support patulin as a viable treatment choice but it did provide a framework for upcoming double-blind clinical trials.

First Clinical Trial using Randomization: 1946

The first randomized curative controlled clinical trial didn't happen until 1946, even though the idea of randomization was originally established in 1923.

The MRC of the UK conducted the first streptomycin randomized control experiment for pulmonary tuberculosis in 1946. A statistical series based on random sampling numbers collected for each gender at each center by Professor Bradford Hill was used to determine whether a patient would be treated with streptomycin and bed rest (S case) or with bed rest alone (C case).

Even though the plan deviated from accepted practices, it immediately became the model for future clinical studies.  

Universal Declaration of Human Rights: 1948

Concern over unintentional abuse of human rights was stated in the Universal Declaration of Human Rights, which was adopted by the United Nations General Assembly.

Clinical Practice Guidelines from the World Health Organization: 1996

The guidelines cover the rationale for a study and its protocol, subject protection, the duties of investigators, sponsors, and monitors, data integrity assurance, product accountability, and the roles of regulatory agencies.