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As some EU countries struggle with the Directive's regulatory demands, emerging markets such as China, India, and Russia continue to bolster their clinical research and drug development programs.
In the early 1980s, Europe was seen by the United States as a mosaic of peoples, cultures, and medical practices. Contrary to the American multicenter clinical trial, the Europeans did not have enough in common to allow clinical data to be shared and collated. The clinical climate in the United States was convinced that the European data would be influenced by the genetic differences among ethnic groups, national differences in the diagnosis of disease, variations in the use of medicinal products for treatment, and differences between health care systems.
Jean-Pierre Tassignon, MD, PhD, FFPM, MBCPM
At the present time, the cross-border Good Clinical Practice (GCP) movement is a reality, and it is driven by sponsors and CROs in need of patients for critically important clinical trials as well as investigators and countries willing to invest in all the drivers of GCP. The drivers include new legislation, GCP inspectorates, ethics committees, curricula in pharmaceutical medicine, conferences, etc. The movement started from regions with advanced GCP legislation and recruited countries with enough resources to meet the same clinical standards.
The movement has been very successful, but it has a price, as we learned in the European Union (EU) following the implementation of the European Union Clinical Trial Directive (EUCTD). Eastern Europe (per capita GDP is 6000–13,000 Euro/year) is capable of paying the price, as the region is undergoing rapid economic growth and its Gross Domestic Product (GDP) per capita is catching up with the West.
Not everyone, however, is capable of paying the price in the EU. In May 2005, one year after its implementation, the European Forum for Good Clinical Practice (EFGCP) held a conference in Brussels on the EUCTD. The conference attendees reported that: a) there was a dwindling number of academic research studies across the Union; b) a proportion of Phase I studies with new medicinal products were exported from the EU to North America; c) statistics about Phase II and III industry-sponsored studies were still inconclusive with regard to judging the impact of the EUCTD; and d) the cost of complying with the EUCTD was expected to impact the hardest on industry-sponsored studies in Phase IV. In this climate, the academic world in Europe was not prepared to comply with the directive's mandates, whereas the pharmaceutical industry was working hard to comply with Phase II and III mandates. At this time and due to the strengthening of the Euro and capacity issues, the Phase I trials could be done in North America. The diminishing return of marketing trials on prescription in Phase IV is probably insufficient to justify a sudden increase in regulatory compliance costs.
The EU rapidly tackled the issue of academic studies by issuing the GCP Directive, which allows member states to accommodate the EUCTD to the specific environment of academic research. However, at this time, it is the speed of implementation of waivers by the member states in their national legislation that remains a challenge.
Dozens of European startup biotech companies that were ready to begin first clinical trials had to postpone their projects, beef up the IMPD, and collect more funds in order to finance additional expertise for clinical trials costs.
The EFGCP conference concluded, with cautious optimism, that the industry-sponsored compartment in European clinical research would regain pre-EUCTD levels of intensity after an adjustment period, and that the academic compartment would do the same after implementation of the new accommodations, if any.
However, given the standards set by the EUCTD, GCP and per capita GDP, which appears to go hand-in-hand, the question still remains open as to whether countries with a per capita GDP below 5000 Euro/year have a chance of joining the drug development movement, with the exception of some specific diseases such as tropical diseases.
At the same time Russia, China, and India have invested in the drug development movement. Russia is witnessing a strong inflow of petrodollars, part of which is being reinvested in the health care system. In May 2005, the EFGCP hosted a delegation from the Chinese State Food and Drug Administration and the Shanghai Municipal Food and Drug Administration. The purpose was to exchange views on systems for ethics review in Europe and in China. This country, with 1.3 billion inhabitants, is readying itself for clinical trials on a grand scale. India is on the same path. Both countries are at the beginning of a Himalayan task, given their GDP per capita per year.
The WHO is further contributing to extend the borders of the GCP world via programs destined to enhance the ethics review capacity in less-developed countries and train investigators in GCP.
The EUCTD is creating a stimulus for the globalization of clinical trials, as the more advanced FDA regulations created a stimulus to export trials from the United States to Europe 20 years ago (trials were somewhat less expensive than in the United States then and quality of clinical research in Europe was improving quickly). GDP per capita in Western Europe was approximately half that in America. Today, Eastern Europe has a per capita GDP approximately half that in the old EU. Eastern Europe is adopting the EUCTD quickly and is increasing its clinical research output. Emergent countries like India and China are at the beginning of developing a clinical research capacity to world standards. A doubling of their GDP per capita within the next decade should bring them to the level of clinical research productivity now observed in Eastern Europe.
Jean-Pierre Tassignon, MD, PhD, FFPM, MBCPM, is chairman, board of directors, European Forum for Good Clinical Practice, Brussels, Belgium; lecturer, Pharmed, Université Libre de Bruxelles, Brussels; and executive vice-president, PSI Pharma Support International AG, Zug, Switzerland.