Impact assessment of the European Clinical Trials Directive: a longitudinal, prospective, observational study analyzing patterns and trends in clinical drug trial applications submitted since 2001 to regulatory agencies in six EU countries

Table 1 Sponsorship and trial-phase specific patterns: AAGR (A) and prior-posterior implementation means (B)

	*All trials*	*CS trials*	*NCS trials*	*Ph I trials*	*Ph II trials*	*Ph III trials*	*Ph IV trials*
A AAGR (Period 2001 to 2009) (%)
IT	+5.0*	+1.3	+13.0**	+32.8**	+6.3*	+1.5	+14.7**
ES	+2.5*	+3.1	+0.7	+2.5	+7.1*	-1.1	+5.5
NL	-1.9*	-2.0*	-1.9	+1.1	-3.8*	-2.8*	-5.7*
DE	-2.3	--	--	-5.3*	-1.6	-4.3*	+6.4
FR	-3.0*	-2.8*	-3.4*	-4.5*	-0.3	-0.7	-7.3**
UK	-5.3*	-0.4	-15.2*	--	--	--	--
B Means (Prior-Posterior Comparison) (n CTA)
IT ¹	587 ⇨ 744*	433 ⇨ 479	153 ⇨ 260*	9 ⇨ 21*	206 ⇨ 280*	311 ⇨ 344	47 ⇨ 87*
ES ¹	576 ⇨ 626	446 ⇨ 556	130 ⇨ 104	90 ⇨ 92	142 ⇨ 175	278 ⇨ 272	67 ⇨ 101
NL ²	697 ⇨ 597*	405 ⇨ 351	292 ⇨ 246	139 ⇨ 126	161 ⇨ 132	203 ⇨ 177	73 ⇨ 67
DE ¹	1,497 ⇨1,428*	(1,300) ⇨ 1,170	(197) ⇨ 259	462 ⇨ 340*	340 ⇨ 321	437 ⇨ 368*	65 ⇨ 144*
FR ³	1,165 ⇨ 973*	885 ⇨ 727*	310 ⇨ 247*	288 ⇨ 221*	291 ⇨ 288	365 ⇨ 350	160 ⇨ 101*
UK ^1,4	1,248 ⇨ 832**	656 ⇨ 576**	592 ⇨ 256**	nd ⇨ (301)	nd ⇨ 353	nd ⇨ 261	nd ⇨ 218

In the case of Germany, exact distribution patterns for sponsorship could not been established for the period prior May 2004, the reported mean (n = 197) refers exclusively to studies initiated by universities or university hospitals. For the UK, trial phase specific distribution patterns prior to 2004 are unknown.
1: IT, ES, DE, UK: Means of three consecutive years prior to implementation (2001 to 2003) versus means for period posterior to implementation (2005 to 2007)
2: NL: Means of three consecutive years 'prior' (2003 to 2005) versus means for years 'posterior' to implementation (2007 to 2009)
3: FR: Means of three consecutive years 'prior' (2001 to 2003) versus years 'posterior' (2007 to 2009). Transition period for implementation of EUCTD in France: 2004 to 2006
4: UK: Means (All trials, CS trials, NCS trials) do not account for phase I trials ('trials with healthy volunteers')
CS/NCS, Commercial/Non-commercial Sponsor; nd, no data; *, significant, defined as P ≤ 0.05; **, highly significant, defined as P ≤ 0.001

ISSN: 1745-6215