Clinical trials: towards good practice.

Quality control, quality assurance, and audit are now an integral, though not always welcome, part of our daily lives. For many years the conduct of clinical trials has relied heavily on trust and the integrity of those involved, and the amount of regulation has been minimal. The introduction of the Declaration of Helsinki in 1964 spelt out the ethical considerations but further changes over the last decade with the introduction of the principles of good clinical practice (GCP) into clinical trials have seen a move towards much closer regulation. References to GCP in this paper relate to research practice in clinical trials and this topic will be examined further in the context of the introduction and implementation of the recent European Community guidelines. The initiatives for the introduction of good practice into clinical trials have come from a variety of sources (originally the Food and Drug Administration in the United States, followed by the pharmaceutical industry worldwide, and the European Community). In the UK guidelines were first produced in 1988 by the Association of the British Pharmaceutical Industry (ABPI). These guidelines were subsequently adopted voluntarily by the UK pharmaceutical industry. Some European countries then followed with their own version of GCP guidelines, for instance the Nordic Group in 1989. It is interesting, however, though there appears to be no clear explanation for the fact that while the ABPI refer to ‘good clinical research practice’ and the Nordic Group to ‘good clinical trial practice’, the European Community guidelines drafted subsequently by the Committee on Proprietary Medicinal Products just refer to ‘good clinical practice’. These guidelines were approved in July 1990 and became eVective on 1 July 1991. The introduction of national legislation in support of GCP has been gradual throughout Europe and, not surprisingly, there remains some confusion over its status and also some variation in how it is regarded between America, Europe, and Japan. Similarly, there is considerable variation from country to country in sanctions which can be imposed for non-compliance. There are, however, hopes that there can be some standardisation and moves have already been made in this direction. The introduction of GCP in the UK is based on the European Community guidelines. There is a danger that the omission of the words ‘research’ or ‘trial’ may lead to confusion between good clinical practice and good clinical care, that is the doctor-patient relationship. So, within the guidelines GCP is defined as ‘a standard by which clinical trials are designed, implemented and reported so that there is public assurance that the data are credible, and that the rights, integrity and confidentiality of subjects are protected’. The guidelines elaborate on how this might be achieved but, in general terms, GCP may be viewed as a gold standard or yardstick for the conduct of clinical trials, which should help to raise standards and also facilitate comparison of clinical trial results. Alternatively, the guidelines might be viewed as a set of management procedures designed to prevent mistakes and fraud and thereby protect the rights of the subject. Fundamental to the concept of GCP is the need for pre-established and systematic written procedures for the organisation, conduct, data collection, documentation, and verification of clinical trials. By means of a carefully documented ‘audit trail’ GCP provides a means of showing that what is claimed has actually been carried out. Sceptics, or busy clinicians, may view the introduction of GCP as yet one more unnecessary hurdle to detract from their normal clinical way of working, and yet another example of excessive bureaucracy which is gradually stifling creativity. Others who see it very much as an imposition from within the pharmaceutical industry may feel threatened or aggrieved at the implied lack of trust, as well as concerned by the seemingly excessive demands. So why is GCP needed in clinical trials? The protection of the subject is paramount and in this respect the guidelines may be viewed as an extension and reinforcement of the Declaration of Helsinki. The safety of the subject, particularly, when using hitherto untested drugs, must be ensured as far as possible. Human beings are not infallible and there must also be assurance about the conduct of clinical trials in terms of an attempt at elimination of cheating, fraud, or accidental error. Problems of poor study design must be avoided. There must be a standard for comparison of trial results given the diversity of settings in which clinical trials operate. This is particularly important in multicentre and multinational trials given the number of personnel and institutions involved. Archives of Disease in Childhood 1997;76:283–286 283