Introduction to Clinical Trials


3. History of Clinical Research Legislation in Europe

Disasters have, in several cases, prompted change in legislation in the US and in Europe. The thalidomide disaster contributed to the publication, in 1965, of the first European Directive, known as 65/65/EEC, enacted by the Council of the European Economic Community. It stated that no medicine could be placed on the market in a member state unless authorisation had been issued by the competent authority in that member state. In essence, pharmaceutical manufacturers had to seek approval for their medicines from each country before marketing could begin in that country.

In 1995, the European System for Marketing Authorisation of Medicinal Products as well as the European Medicines Evaluation Agency (EMEA), was established. Evaluation of applications and elaboration of guidelines was undertaken through the incorporation of the Committee for Proprietary Medicinal Products (CPMP) and the Committee for Veterinary Medicinal Products (CVMP). The centralised procedure eliminated the need for individual member state review - as one approval is given to cover all member states.

The mutual recognition procedure (MRP) and the decentralised procedure (DCP) are used for those medicines not authorised by the centralised procedure. They are similar to the former procedure where an applicant goes directly to a single member state. Once the medicine is approved by that authority, the applicant then seeks to have other member states recognise the approval and grant their own marketing authorisation (MRP) or member states collaborate directly on an application submitted (DCP). In 2004, the full name of the agency was shortened to the European Medicines Agency (EMA). The CPMP was renamed the Committee for Medicinal Products for Human Use (CHMP).

The ICH-GCP guideline, developed in 1996, sets an international harmonised quality standard that protects the rights, safety and welfare of human participants. It minimises human exposure to investigational products, and improves quality of data, with the aim of speeding up development of new medicines and decreasing the cost to sponsors and to the public. Compliance with this guideline provides public assurance that the rights, safety and well-being of trial participants are protected and consistent with the principles of the Declaration of Helsinki. It also assures that the clinical trial data are credible.

There are 13 core principles of ICH-GCP as cited below:
  1. Clinical trials should be conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).

  2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

  3. The rights, safety and well-being of the trial subject are the most important considerations and should prevail over interests of science and society.

  4. The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.

  5. A clinical trial should be scientifically sound, and described in a clear, detailed protocol.

  6. A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/ independent ethics committee (IEC) approval/favourable opinion.

  7. The medical care given to, and medical decisions made on behalf of subject should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.

  8. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).

  9. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

  10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.

  11. The confidentiality of records that could identify subject should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).

  12. Investigational products should be manufactured, handled and stored in accordance with applicable Good Manufacturing Practice (GMP). They should be used in accordance with the approved protocol.

  13. Systems with procedures that assure the quality of every aspect of the trial should be implemented.