History And Evolution In Clinical Research
Let's start with the famous quote of Aldous Huxley : "The charm of history and its enigmatic lesson consist in the fact that, from age to age, nothing changes and yet everything is completely different."
Clinical Research has evolved a long way since its inception, whether documented or not. It traverses a long and amazing journey. The recorded history of clinical trials dates back to the biblical descriptions of 500 BC. The journey encompasses from dietary therapy - legumes and lemons - to drugs.
Ranging from the first recorded trial of legumes in biblical times to the first random and controlled trial of streptomycin in 1946, the history of clinical trial had seen a wide variety of challenges : scientific, regulatory and ethical.
Clinical trials saw the birth and period of the names that ranges from Egyptian Imhotep to James Lind. As the scientific advances continue to occur, there will be new ethical and regulatory challenges requiring dynamic updates in ethical and legal framework of clinical trials.
This article highlights the major milestones in the evolution of clinical trials.
Pre Lind era:
The Old Testament depicts that King Nebuchadnezzar II ordered the children of royal blood to eat only meat and wine for three years. Daniel requested that he and three other children would be allowed to eat only bread and water. Noticeably Daniel and the three children were healthier and more lively than those who were given the wine and meat diet.
Ambroise Pare,a Renaissance surgeon, unintentionally carried out a clinical trial when ceased to continue the standard treatment of boiling oil for open wounds. He experimented by making a mixing of egg yolk, turpentine and oil of rose and applied to the wounds. Surprisingly noticed that the wounds treated with this mixture healed well compared to those which became swollen and infected with the standard treatment.
Lind and trial of scurvy:
James Lind is markedly considered the originator of the modern clinical research trial because he
was the first to introduce the use of a control group. He conducted the trial on a group of sailors suffering from scurvy. He prescribed same diet to all but fed one additional item such as cider and vinegar to one group and fed the other group with lemon juice. The group who took the lemon juice supplement recovered from scurvy in just six days.
Arrival of Placebo:
Placebos were first used in clinical trials and emerged as important tools in medical research. Placebos are non-effective medical treatments given to control groups to compare the results with those from the novel drug.
Randomization or blind clinical trials were introduced. This involves giving random treatments to participants one being a placebo and the other a new drug. Its called blind trial because neither group knew which treatment received.
This period saw the introduction of multi-center clinical trials where multiple studies are conducted at various sites; but all use the same protocol to get wider testing and better statistical data.
Evolution of ethical and regulatory frameworks
The Nuremberg Code was developed that outlines 10 basic statements for the safety of human participants in clinical trials.
The Declaration of Helsinki was developed that outlines ethical codes for physicians and safety of participants in clinical trials worldwide.
The U.S. FDA was given more authority and accountability over the approval of novel drugs and treatments.
Assembly of the International Conference on Harmonization (ICH) to provide help and eliminate differences in drug development requirements for three global pharmaceutical markets: U.S. and The EU, Japan. The ICH initiates promoting increased efficiency in the development of novel drugs and making them more available to patients and the public.
A Common Technical Document (CTD) was developed. The CTD acts as a standard casebook used in Europe, Japan and the U.S. for proposing data gathered in clinical trials to respective governing authorities.