Harmonised but not more attractive? The EU Clinical Trials Regulation and the site allocation of multinational drug trials
Despite successfully harmonizing authorization timelines across the EU, the Clinical Trials Regulation failed to increase the region's attractiveness for multinational industry trials, as evidenced by a significant decline in the probability of trials including EU sites post-implementation, suggesting that further harmonization alone cannot address the underlying high fixed costs of entering the European market.
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Before a new medicine can reach a pharmacy shelf, it must pass through a rigorous gauntlet of testing known as clinical trials. These are large-scale studies where researchers give a drug to volunteers to see if it is safe and effective. For a pharmaceutical company, deciding where to run these trials is a massive strategic choice. The location determines which patients get early access to the treatment, which countries build up their medical research capabilities, and which governments gather the evidence needed to decide if the drug should be covered by health insurance. For years, Europe has been losing ground in this global competition. While companies once ran a large portion of their trials on the continent, that share has been shrinking for a decade, with many sponsors turning instead to Asia and other regions.
In response to this decline, the European Union introduced a major new rule called the Clinical Trials Regulation. The idea was to fix a broken system. Previously, if a company wanted to test a drug in ten different European countries, it had to file ten separate applications, each with its own paperwork, fees, and timeline. This fragmented process was slow and expensive. The new regulation replaced this patchwork with a single, unified application system. A company could now submit one dossier to a central portal, and a designated lead country would coordinate the review for the entire group. The goal was to harmonize the process, making it faster and easier to run trials across multiple European nations at once.
A researcher named Can Apaydın set out to see if this new system actually worked as intended. Using a massive dataset of nearly thirteen thousand multinational drug trials that began between 2013 and 2025, the study compared what happened in Europe before and after the new rules became mandatory. The analysis looked at whether companies chose to include European sites in their trials, how many different countries they used within Europe, and whether the new system helped slower countries catch up to faster ones. The findings reveal a surprising twist: while the new rules successfully made the approval process more uniform across the continent, they did not make Europe more attractive to drug companies. In fact, after the new system became mandatory, the likelihood that a multinational trial would include any European site at all dropped significantly.
The study shows that the new regulation achieved its technical goal. It nearly eliminated the differences in how long it took for different countries to approve a trial. Under the old system, approval times varied wildly from country to country, creating a confusing landscape for sponsors. The new system smoothed these differences out, bringing the decision time for all member states to a common median of roughly four months. However, this harmonization came with an unintended side effect. The research suggests that the new system raised the fixed cost of entering the European market. Instead of filing separate, manageable applications, companies now face a single, complex, and highly transparent process that requires navigating a new digital platform and adhering to strict disclosure rules. For many sponsors, particularly those running early-stage trials or those with smaller operations, this new barrier was too high.
As a result, the data shows a clear shift in behavior. After the new rules took full effect, the probability that a multinational trial included any European site fell by between 3.9 and 11.5 percentage points compared to other regions of the world. This decline was most pronounced in early-phase trials, which are smaller and more sensitive to delays and costs. While the trials that did remain in Europe tended to use a slightly larger number of countries than before, this was not because companies were adding new sites out of enthusiasm. Rather, it appears that the companies that left Europe entirely were the ones that would have used the fewest countries anyway. The remaining trials, which were often larger and more established, simply spread their existing European footprint across more nations because the cost of adding an extra country had gone down.
Crucially, the study also found that the new system did not achieve a secondary hope: it did not help the slower countries catch up. Before the reform, some nations took much longer to approve trials than others. The expectation was that once the timelines were equalized, sponsors would start choosing these previously slower countries more often. The data, however, showed no such shift. The countries that used to be slow did not gain a larger share of trials. This indicates that the speed of approval was never the main reason companies chose one country over another; instead, they were driven by the availability of patients and the strength of local research teams.
The research concludes that the European Union's effort to streamline its clinical trial regulations succeeded in making the process more consistent but failed to reverse the continent's decline in global trial activity. The new system removed the friction of dealing with different national rules, but it introduced a new, higher barrier to entry that discouraged companies from bringing their trials to Europe in the first place. The evidence suggests that simply making the rules the same across borders is not enough to win back the market. To make Europe attractive again, future reforms may need to focus on lowering the initial cost and complexity of entering the region, rather than just harmonizing the procedures that follow.
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