Good Clinical Practice (GCP) is defined in the International Conference on Harmonization (ICH) guideline as an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. This standard ensures that the rights and safety of the trial subjects are protected and that the trial results are credible.
A Brief History
ICH-GCP (International Conference on Harmonisation - Good Clinical Practice) came into existence in 1996. However, there were a number of medical events and other legislative actions that led to the guideline we now refer to as ICH-GCP.
The first action taken by a government to control the way drugs were put on the market is the Pure Food and Drug Act of 1906, in the USA. In this law is stated the following: 'An Act for preventing the manufacture, sale, or transportation of adulterated or misbranded or poisonous or deleterious foods, drugs, medicines, and Liquors, and for regulating traffic therein'. In short, it imposed regulations on the labelling of products containing alcohol, opium, morphine, cocaine and some other substances. On each product it needed to be indicated which substances were contained in the product and the quantity.
In 1937, a disaster occurred that proved that this Act was insufficient: the so-called Sulfanilamide incident in the US. Sulfanilamide was a product that was used in the battle against streptococci. It was sold as a child's syrup by dissolving it in ethylene glycol, also known as antifreeze (hence the disaster). As a response to this, the US government revised the Pure Food and Drug Act of 1906. This became the Food, Drug and Cosmetic Act of 1938. It introduced, besides stricter regulations on labelling, safety standards and required that new drugs were tested on safety before marketing.
Following WWII and during the Nuremberg trials, it became clear what atrocities the Nazi doctors committed 'in the name of medical science'. During their trial the Nazi doctors argued in their defence that there was no international law or informal statement that differentiated between legal and illegal experiments on humans. On 17 April, 1947 two US doctors who worked for the prosecution on the trials, submitted a text with six points defining legitimate research. These six points became ten points and are now known as the Nuremberg Code. Although it never had any well-established legal force, it still is one of the foundation stones for ICH-GCP.
Listed below are the ten points of the Nuremberg Code:
- Voluntary consent of the subject
- Results should be fruitful and not procurable by other methods
- Trial design should be based on the results of animal experimentation
- Avoid unnecessary suffering and injury
- If the researcher believes that death or disabling injury may occur during the trial, the research is not legitimate and should not be done
- The degree of risk may not exceed the benefits of the experiment
- Every possible action must be taken to protect the subject from injury, disability or death
- The experiment should be conducted by scientifically-qualified personnel
- The subject may terminate the trial at any stage
- The investigator must be prepared to terminate the trial at any stage
These ten items were later incorporated in the Declaration of Helsinki, written in 1964 by the World Medical Association (WMA), an international organisation representing physicians. The declaration was a guideline that provided the highest ethical standards at that time.
All these documents formed the basis of Good Clinical Practice, but what about Harmonisation? The onset for this was the Thalidomide incident.
During the 1960s, Thalidomide was used in Europe as a treatment for insomnia, mostly in pregnant women. When the company who manufactured the drug made a submission to the FDA (US Food and Drug Administration) to market the drug on the American market, Frances Kelsey (an FDA employee) reviewed the application thoroughly and kept if off the market when she discovered that it caused birth defects when used on pregnant women.
The consequence was a tightening and amending of the Food, Drug and Cosmetic Act of 1938. Eventually, from the mid-1970s, the FDA found it necessary to reject clinical research from other countries, since they didn't have the same ethical and safety standards as the US. Europe and Japan each developed their own set of GCP guidelines, from the mid-1980s onwards. But the differences between the US, Europe and Japan remained and did not contribute to the economical efficiency of clinical trials: pharmaceutical companies had to invest in three different trials to globally market one single drug.
In 1996, an International Conference on Harmonisation (ICH) was called into being, consisting of authorities of Europe, US and Japan and experts form the pharmaceutical industries. This led to an international, uniform standard to accept the results of clinical trials, as long as they are conducted according to the ICH-GCP guidelines on Safety, Quality, Efficiency and Multidisciplinary.
Recently the ICH - GCP guideline has evolved from an economical incentive to a political and legal incentive. Several countries, with the EU in the lead, are incorporating GCP in their legislation. Before this, companies were inclined to conduct clinical trials according to ICH-GCP out of an economic motive: this way they only had to perform one trial instead of three and it was much easier to get a new drug accepted and marketed globally. Now it can become illegal when a trial is not compliant with ICH-GCP and subjects are more protected.