Good Clinical Practice / GCP

Experimental medicines have been tested on humans for many years to determine safety and efficacy information.  However,  basic ethical and scientific principles have not always been observed, therefore efforts have been made over several decades to codify rules that have to be followed in medical research on humans.

Following the darkest chapter of medical experiments on men conducted by the Nazis, the “Nuremberg Code”, defined during the “doctors’ trials” after the second World War, stated 10 principles for the conduct of proper medical research.   Basic principles of the Nuremberg Code included the obtaining of “informed consent” i.e. the idea that participation of a person in medical experiments is only acceptable if the person has been informed about the concept and risks of the trial and has agreed to participate.

In 1965, the World Medical Association, the most influential international physicians’ organisation, adopted the Declaration of Helsinki, which summarises the ethical principles of research based on the Nuremberg Code.   This declaration has undergone several revisions over the last 50 years to keep in line with developments in clinical research.  In addition to the requirement to obtain the informed consent of patients before participating in a clinical trial, the Declaration requires that the trial is conducted in accordance with a written study protocol.   The 1975 version, introduced the concept that all medical research needed to be reviewed by Independent Ethics Committees before being started.  The ethics committees have to assess if the rights of the participants are respected, and if the risk for the patients justifies the supposed benefit of the research.

To ensure that new medicines were developed according to comparable standards, regulatory authorities and pharmaceutical industry associations from the USA, the European Union and Japan created the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) in 1990.   In 1996, the ICH adopted a guideline for Good Clinical Practice (ICH-GCP) which has become the worldwide gold standard for clinical research with pharmaceuticals and biologicals.  Its key points are again to ensure the protection of trial participants and the quality of trial data.   ICH-GCP provides more detailed rules on the conduct of clinical trials.

The guideline describes responsibilities of the Independent Ethics Committee, the investigator (the physician who performs experimental treatments) and of the sponsor (the person or institution, who apart from financing is responsible for trial design, organisation and data evaluation).
Ethics Committees (or Independent Review Boards in the US) receive guidance about their composition i.e. number of members and backgrounds, and the documents and aspects of the trials that should be reviewed before giving an ethical decision.  The sponsor must receive documented approval for the study by both the Ethics Committees and the national regulatory body where the trial is to be conducted, before allowing any subjects to be dosed with the new investigational product.

Trial investigators are expected to follow the approved written protocol and documented study procedures, and to respect the rights of the participants.  Therefore, they can only participate in a trial, if they have adequately qualified and trained staff, and if they have appropriate equipment as required for a particular study.

The sponsor has the obligation to monitor the trial, i.e. to send out qualified personal to verify at the investigator’s site (normally a hospital or a general practice) if the protocol has been followed, and if the data sent to the sponsor corresponds to the data documented at the site.

The conduct of clinical trials according to Good Clinical Practice guidelines has opened the possibility for a reciprocal recognition of trial results globally, and thus avoiding the repetition of trials in different regions of the world.