History of Clinical Trial: Part 1

Clinical Trial

Nowadays, Medical Science is progressing swiftly. With the help of advanced technology, dedicated researchers are continuously discovering new treatment strategies, medical devices, drugs, etc. Pharmaceutical companies invest a lot in these. The discoveries are followed by clinical trials, which are conducted very carefully to answer the following questions:

·?????? How does the new treatment work?

·?????? Does it work better than other existing treatments?

·?????? Does it have side effects or adverse effects?

·?????? Can the standard treatments or current, approved treatments be used in different ways to make them more effective, easier to use, or decrease certain side effects?

·?????? Can a treatment be used on a different population, for which the treatment was not previously tested, such as children?

·?????? Effectiveness of prevention strategies, such as dietary changes, lifestyle modifications, etc.

Now, a clinical trial is a multiphase study conducted by medical researchers. First, the tests are done on the cells in the laboratory or animals and then on humans.

New Drug Application (NDA):

If clinical trials can give satisfactory answers, then the pharmaceutical companies apply to the regulatory bodies to get approval for marketing the drug. This process is called new drug application or NDA. Regulatory bodies review minutely the details of the discovery and clinical trial process. If they find it satisfactory, they permit the companies to market the drug. Otherwise, they ask for the required change in the process.

Many rules, regulations, and ethics are being followed during clinical trials. The purpose is to ensure the safety of human lives.

The Reason behind Making Clinical Trial Mandatory

The modern form of clinical trials is not very old. There were almost no rules for testing the drug's effectiveness before marketing it. Many tragedies happened in the early 20th century due to harmful, poisonous drugs. These sad incidents became the driving force for the formation of today’s strict clinical trials.

First Evidence of Clinical Trial in Human History

It is the inherent tendency of humans to be curious. The ancient scriptures of human history (like the Upanishads, Vedas, Bible, etc.) also give pieces of evidence of human efforts to improve health, economy, relationships, spiritual understanding, etc.

The “Book of Daniel” in The Bible, describes the reign of King Nebuchadnezzar of Babylon. He was very conscious about the health of his subjects. He believed that eating only meat and drinking wine would keep them fit. He forced them to stop eating vegetarian foods.

But some vegetarian youth from the royal family objected to it. Then King planned an experiment to compare the effects of vegetarian foods with meat and wine. He allowed the rebels to eat only vegetarian food for 10 days. After this, their health conditions were compared with the other meat eaters.

After a health check-up, the vegetarians appear more nourished and healthy. Then the King allowed them to continue their vegetarian diet.

This one is probably the first evidence of an uncontrolled open clinical trial in human history, which guided the King to decide on public health.

Beginning of the Modern Clinical Trials with Dr. James Lind

The most common type of modern clinical trial is parallel-arm experiment. Here all the subjects must have almost similar health conditions. Then they are divided into two groups. One group receives the new treatment and other groups either receive no treatment or receive the old standard treatment.? The outcomes of both groups are compared at the end of the treatment.

British physician Dr. James Lind was the first person to conduct a parallel-arm medical experiment. He is considered the true Father of Clinical Trials.

During the 18th century, Scurvy was a very common disease among the soldiers who sailed through the ocean. The impact of Scurvy was more dangerous than any enemy attack. The symptoms of scurvy were putrid gums, unhealed fungus

flesh, fatigue, severe cardiac problems, etc.

The sailors used to go on long expeditions. They remain highly deprived of healthy fruits and vegetables in their diet and clean environment. The exact reason for Scurvy was unknown for a long time. Most of the physicians blamed the malnutrition and foul air during the sea voyage. Dr. James Lind was also one of them. He also suffered from Scurvy. Using his knowledge, experience, and intelligence, he tried to invent a treatment for Scurvy.

He selected 12 soldiers severely suffering from Scurvy. He divided them into 6 groups of 2. Each group was given a different intervention:

·?????? Group 1: Citrus fruits-- Previously Lind had observed that sailors who had been fortunate enough to acquire fresh citrus fruits during their stay at home often recovered from scurvy.

·?????? Group 2: Drinking vinegar—It has some medicinal properties and was used for treating various ailments during that period.

·?????? Group 3: Drinking seawater—There was a belief that drinking sea water could cure Scurvy.

·?????? Group 4: Ingesting ‘Rob’—Rob was a medicinal syrup used at that time. It was a liquid mixture of barley water, fruit juice, and spices.

·?????? Group 5: Consuming Elixir Vitriol-- It was diluted sulphuric acid.

·?????? Group 6: Eating a Mixture of Garlic, Mustard Seed, Urticaria, and Balsam of Peru. It was given because it was a source of various vitamins, minerals, and other nutrients.

Results:

Significant improvement from the Scurvy symptoms was found in the group taking citrus fruits.

It made very clear that the incorporation of vitamin C in the diet is very important for treating Scurvy. Within a very short time, sailor soldiers stopped completely to become sick due to Scurvy. James Lind’s treatment worked like magic.

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References:

1.????? https://www.sciencepharma.com/blog/the-changing-face-of-clinical-trials-a-long-and-fascinating-journey-to-effective-and-safe-medicines/

2.????? https://xceneinnovate.com/the-evolution-of-clinical-trial/