Who's afraid of the European Clinical Trials Directive?

Abstract

Wouldn't it be nice if the approval and monitoring of clinical research done in the many, varied, and ever-increasing number of European countries could be simplified and streamlined? This deceptively simple idea was first mooted well over a decade ago and by 1995 the European Commission had published a concept paper for a European Directive on Implementing Good Clinical Practice. Several complex rounds of negotiation between the various European legislative bodies followed and the result, Directive 2001/20/EC, was officially adopted on April 4, 2001. The race is now on for Europe's member states to incorporate the Directive into domestic legislation, since compliance will be mandatory as of May, 2004. Most European countries published draft legislation earlier this year. Somewhat belatedly, some of Europe's academic clinical investigators have started to voice fears about how the Directive might stifle their research. The essential aims of the Directive are to harmonise the various national administrative procedures necessary to start a clinical trial and to set pan-European legal standards of protection for all clinical trial participants, including healthy volunteers. Non-interventional trials will be exempt. The Directive was initially conceived and drafted as a way of facilitating commercial drug development to give Europe's pharmaceutical industry a competitive edge. Only in the later stages of negotiation was some acknowledgment of the different nature of noncommercial research made. The final text thus states that: “Non-commercial clinical trials conducted without the participation of the pharmaceutical industry may be of great benefit to the patients concerned”, and notes that the Directive should “take account of the special position” of such trials with regard to the manufacture, packaging, and labelling of medicinal products. The catch is that in all other respects publicly funded clinical trials must fulfil the same requirements as their commercial counterparts. According to the Directive no interventional research may be initiated without a sponsor—“an individual, company, institution or organisation which takes responsibility for the initiation, management and/or financing of a clinical trial”. The notion of a sponsor is familiar to commercial research. Publicly funded research ventures are by contrast collaborations where partners oversee different aspects of a trial but no one person or organisation is required to take overall responsibility. The inscription of this requirement into law will expose the single sponsor to the risk of litigation, a risk that charities, universities, and other publicly funded research bodies are unsurprisingly unwilling to take. It will be the sponsor's role to apply for trial authorisation and ethics-committee approval, activities currently the responsibility of the principal investigator. Ethics committees will be obliged to give an opinion within 60 days of receipt of a standard trial application. The Directive provides the first European description and enforcement of the responsibilities of ethics committees, which include not only trial authorisation but also long-term monitoring. Serious concerns have been raised as to whether the ethics committees of Europe are sufficiently equipped and funded to take on these added responsibilities. Legal compliance with Good Clinical Practice for all trials will also be mandatory under the Directive, which means that publicly funded investigators face the same intensive site monitoring and source-data verification as are currently standard in industry. Non-commercial research organisations claim that substantial new investment will be needed to put in place the infrastructure and staff—which the commercial sector already has—for the increased administration and documentation required by the Directive. Critics counter that this is knee-jerk panic at the threat of change and greater monitoring, and a convenient excuse to bemoan lack of funding. Who is right? The following quote about UK-based clinical trials is instructive. “Despite the stated purpose of the Directive it is clear that the planned changes in the UK and the rest of Europe will not simplify, and are unlikely to result in substantial harmonisation of, the current regulatory procedures for the conduct of clinical trials. There are many new requirements that will place an administrative burden on both sponsors of clinical trials and on regulators.” This statement comes not from a UK academic body but no less than the Association of the British Pharmaceutical Industry. It follows that if the commercial sector, in whose interests the Directive is principally drafted, forecasts an intolerable increase in red tape, publicly funded investigators are right to be very afraid indeed.