Impact of Current CTD
DG Sanco acknowledged that CTD was a factor in the declining number of European clinical trials. The number of clinical trials performed in the EU fell nearly 17% between 2007 and 2010, sinking from 5,028 to 4,193. The number of clinical trial applications in the EU during most of the period slipped almost 13% from 9,948 in 2007 to 8,672 two years later (a 2010 figure was unavailable). Interestingly, clinical trial declines were evident across all four phases. Phase I trials skidded 8.4% from 1,510 in 2007 to 1,383 in 2010. Declines were 22% in Phase II, Phase III, and Phase IV, where the number went from 904 to 707.
That decline is less evident when you look only at clinical trials involving only EU member states, which account for 25% of EU clinical trials. For example, the number of two-nation trials jumped from 229 in 2007 to 364 the next year, then dipped to 238 in 2009, which was still 4% above two years earlier. Trials involving most EU members saw increases, though totals were very small: the number of 19-nation trials, for example, jumped from one in ’07 to five the following two years.
Declines in trials are evident in the U.K. In 2006, Cancer Research UK (CRUK) carried out a study into CTD’s impact on the costs and conduct of noncommercial U.K. cancer trials. The study concluded CTD had doubled the cost of running clinical trials in the U.K. and delayed the start of trials, Layla Theiner, CRUK’s European public affairs manager, told GEN.
“The lack of central guidance, the lack of clarity over how to interpret the guidance notes, and the unnecessary increase in paperwork are all of major concern to our researchers,” Theiner added. “And the trial units were unable to open trials in non-U.K. centers because of the different interpretation of the CTD by member states.” Peter Johnson, CRUK’s chief clinician, offered a stark picture of CTD’s impact, telling the Daily Telegraph in February that the U.K.’s share of trials worldwide dropped from 6% to 2% since the directive was introduced.
Johnson blamed CTD for drug companies pulling jobs out of Britain. Last year AstraZeneca closed a research campus near Loughborough while Pfizer began a two-year shutdown of its Sandwich R&D center. But that’s just as likely due to patent expirations of blockbusters; Eli Lilly launched a new neuroscience research site at its Erl Wood R&D campus in Surrey, while GlaxoSmithKline and University of Nottingham will establish a drug development sustainable chemistry lab in the country.
Job fluctuations have many explanations, so they are harder to blame on CTD than reduced clinical trial activity. Participants in planned clinical trials within the EU fell by 26%, from 535,481 in 2007 to 396,784 in 2010. When multinational trials including at least one EU site are counted, the patient count fell 15% from about 1.02 million in 2007 to 866,155 in 2010.
So CTD should be overhauled. But any proposals to do so should be accompanied by solid projections of how much the new rules will save in time and money, since industry and medical groups have identified both as being wasted by the status quo. The more substantial the savings, when balanced by safety and quality concerns, the better the odds of at least some clinical trial activity returning to the continent. However, there is no guarantee that an overhauled CTD will beat a path to Europe’s proverbial door, at least not as long as the biopharma industry continues to look to China and other emerging nations for future growth.