Research Article: The Unintended Consequences of Clinical Trials Regulations

Date Published: November 17, 2009

Publisher: Public Library of Science

Author(s): Alex D. McMahon, David I. Conway, Tom M. MacDonald, Gordon T. McInnes

Abstract: Alex McMahon and colleagues critique the International Conference on Harmonisation (ICH) guidance on good clinical practice (GCP), arguing that it is having a disastrous effect on noncommerical randomized clinical trials in Europe.

Partial Text: The experience of clinical researchers worldwide indicates that a major obstacle to undertaking academic research is the ever-increasing bureaucracy attached to the process. Recent changes in research governance were intended to ensure that clinical trials are safe and informative. However, the regulatory burden is now obstructing high quality science and has become the biggest single threat to research carried out in academia [1]. We illustrate here this international problem by reference to the regulations imposed by the European Union and the incorporation of these restrictions into UK national law concerning Good Clinical Practice (GCP).

By May 2004, The European Directive 2001/ 20/ EC on clinical trials (“The Directive”) had been adopted across the European Union [4]. Implicit in the title of The Directive is the implementation of GCP and articles of The Directive include informed consent, ethics committees, reporting of adverse events, and national inspection of trials. The Directive was incorporated into the law of the United Kingdom in the Medicines Act [5] and is described on the Medicines and Healthcare Products Regulatory Agency (MHRA) website [6]. “The conditions and principles of GCP which apply to all clinical trials” are “based on” the ICH guideline. The European Directive 2005/28/EC attempts to provide more detailed guidelines on GCP [7]. This GCP Directive instructs that the ICH guideline on GCP should be “taken into account.” The content of this directive appears advisory rather than prescriptive. Whether it was intended for academic clinical trials to be included is uncertain. The Medicines Act stipulates only the general principles section of ICH rather than the more detailed sections [5],[6]. The GCP Directive states that noncommercial research as carried out by public bodies can “make the application of certain of the details of good clinical practice unnecessary or guaranteed by other means,” with member states “providing for specific modalities.” However, the eventual draft guidance mainly discusses treatment labelling and trial documentation [8].

The academic and public research communities were alarmed at the prospect of the directive of May 2004 [13]–[17]. These regulations were clearly created for the benefit and/or regulation of the pharmaceutical industry [18],[19], and it was inevitable that the number of noncommercial trials would decrease [20]. It was also anticipated that the pharmaceutical industry itself would avoid the extra costs by moving trials out of Europe and into less developed countries [21]. The potential problem for noncommercial research was clearly recognised by the MHRA, which appeared powerless to intervene [22]. A second GCP Directive followed and three UK laws were passed to implement these Directives. The process for ever-increasing bureaucracy appears to be on-going with no sign of conclusion. In the meantime there has been real damage to patient care across the European Union. The EU was warned that the directive would severely impair trials in emergency medicine, because of the difficulty of obtaining a legal representative to give informed consent [23]. The problem with the directive was first recognised in Austria [24], but applies to the whole of Europe and was not resolved in the UK until 2006.

Drug trials initiated in academia have similarities with conventional pharmaceutical company trials but also important differences. The primary aims of academic trials are to improve patient care rather than to develop new pharmacological entities. Surely, these objectives are of equivalent or of greater importance to society? In the conduct of both types of trial, GCP is important but the need for intrusive bureaucracy to ensure harmonisation is much less relevant to academic studies usually carried out at a single site. In the past, the pharmaceutical industry might have sponsored such research but The Directive makes this much less likely. The requirements of The Directive have dissuaded Universities from taking on this role. Accumulating evidence suggests that many research units and individual researchers have withdrawn from noncommercial randomised clinical trials altogether because of The Directive.



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