Conducting Clinical Trials Beyond Europe

Routine inspections and regulations can help maintain GCP standards in global trials.
Oct 01, 2010

Peter O'Donnell
Every now and then it's good to step back and take a broader view. The natural focus of Brussels tends to be introverted—as was so tellingly demonstrated, for instance, by the September spats about French treatment of Roma. French President Nicolas Sarkozy was struggling to win popular support in the run-up to national elections by forcibly repatriating immigrants from Eastern Europe under the slender pretext of criminality. When the European Commissioner for Justice publicly criticized these actions, Sarkozy's response was "Are you ready to take them in your country?" And the chattering classes in Brussels became obsessed with discussions of the legal details of whether citizens of Romania, Bulgaria, and Slovakia—all of them EU member states—could legitimately be "repatriated," and on what grounds.

All very spirited, of course, but none of it really contributing towards any type of solution to the long-standing challenge of integrating—or at least not discriminating against—millions of marginalized European Union citizens.

A similar introversion is evident in European discussions of clinical trials. The need for reform of the EU clinical trials directive, the fine-tuning of the new pharmacovigilance rules, the limits on what adverse drug reaction information the European Medicines Agency (EMA) could, or should, disclose. These are topics that have absorbed political attention in Brussels, almost to the exclusion of any other consideration.

Consequently, it is a breath of fresh air to look for a moment beyond the shores of Europe, and beyond the confines of one of the richest corners of the world, and to consider the relation between clinical trials and those who live in far less comfortable conditions.

In early September, the EMA held a three-day international workshop to discuss a global framework of clinical trials. The heart of the discussions was how to protect the rights, safety, and well-being of patients participating in clinical trials anywhere in the world. Some 170 participants from around 50 countries from the Americas, Asia, Africa, and Europe came to London, representing patient organizations, health-related non-governmental organizations, clinical trial sponsors, the pharmaceutical industry, ethics committees, regulatory authorities from all continents, and intergovernmental organizations.

The workshop was part of the consultation process on a reflection paper from the agency on ethical and Good Clinical Practice aspects of clinical trials conducted in third world countries and used in support of marketing authorization applications to the agency. The motivation is administrative as much as humanitarian, but is nonetheless to be welcomed. As the agency points out, with the increasing globalization of clinical research, less than 40 percent of patients enrolled in pivotal clinical trials for marketing authorization applications to the agency received their treatments at clinical trial sites in western Europe. These trials involved more than 44,000 clinical trial sites in 89 countries. As Fergus Sweeney, head of inspections at the agency, put it: "Wherever in the world we stand, the majority of clinical trials are being conducted somewhere else in the world, under a different regulatory framework and in different cultural settings."

The practical problem from this is, he went on, that "we all rely on the same trials to make decisions: as regulators, to allow or disallow marketing authorizations, and as patients and healthcare providers, to use or not to use a medicine." But the quality of the trials may not always be the same.

And from a broader humanitarian or ethical perspective, there are challenges too. As the meeting took its course, some consensus emerged around the conviction that EU regulators should never accept (or require) studies conducted beyond the EU that would be ethically unacceptable in the EU. There should not, became the refrain, be a different standard applied to trials conducted in the EU compared to those conducted elsewhere.

Achieving this refined state will depend, participants underlined, on cooperation and networking between regulatory authorities and ethics committees involved in the supervision of clinical trials. It will also require greater transparency of clinical trials, including clinical trial registries and the provision of information about ethical and GCP aspects in the European Public Assessment Report that the agency produces on each application it processes. In addition, patients will have to be involved early on in the design of protocols, to ensure the adequate protection of clinical trials subjects, participants suggested.