1 00:00:15,014 --> 00:00:16,383 >>Anabela Marcal: Hello everyone. 2 00:00:16,449 --> 00:00:17,917 My name is Anabela Marcal. 3 00:00:17,984 --> 00:00:20,086 And I'm the European Medicines Agency 4 00:00:20,153 --> 00:00:23,189 liaison official to the U.S. Food and Drug Administration. 5 00:00:24,257 --> 00:00:28,228 I have been at the European Medicines Agency for 24 years. 6 00:00:28,294 --> 00:00:31,731 And I have different roles including in clinical trials, 7 00:00:31,798 --> 00:00:33,933 pharmacovigilance, and inspections. 8 00:00:35,101 --> 00:00:37,971 In this lecture, I'll give you a broad overview 9 00:00:38,037 --> 00:00:40,507 of the European Union regulatory framework 10 00:00:40,573 --> 00:00:44,010 for the authorization and supervision of clinical trials. 11 00:00:54,020 --> 00:00:57,757 In this lecture, I will mainly focus on the legal framework 12 00:00:57,824 --> 00:01:00,794 for the authorization of clinical trials in the E.U., 13 00:01:01,494 --> 00:01:05,832 and, in particular, the new E.U. Clinical Trials Regulation 14 00:01:06,366 --> 00:01:07,600 and its business tool, 15 00:01:07,667 --> 00:01:09,836 the Clinical Trials Information System. 16 00:01:10,904 --> 00:01:13,940 I will also touch on publication provisions, 17 00:01:14,007 --> 00:01:16,075 drive it from this new regulation, 18 00:01:16,142 --> 00:01:19,245 which increased greatly transparency. 19 00:01:21,514 --> 00:01:23,716 Finally, I'll give an overview 20 00:01:23,783 --> 00:01:25,885 of the accelerating clinical trials 21 00:01:25,952 --> 00:01:29,956 in the E.U. initiative, which is a business initiative 22 00:01:30,023 --> 00:01:33,226 to transform the E.U. clinical research environment. 23 00:01:38,364 --> 00:01:41,100 This slide shows how the legal framework 24 00:01:41,167 --> 00:01:43,236 for the authorization of clinical trials 25 00:01:43,303 --> 00:01:44,971 has progressed in the E.U. 26 00:01:45,905 --> 00:01:48,975 Pre-2004, there was no harmonization. 27 00:01:49,042 --> 00:01:52,312 All clinical trials or authorization of clinical trials 28 00:01:52,378 --> 00:01:55,715 was following national rules and different process 29 00:01:55,782 --> 00:01:57,383 in each Member State. 30 00:01:58,384 --> 00:02:02,889 In May 2004, there was a Clinical Trials Directive 31 00:02:02,956 --> 00:02:06,159 adopted that brought some harmonization, 32 00:02:06,226 --> 00:02:09,128 but still a lot of national systems 33 00:02:09,195 --> 00:02:12,465 and process varied amongst Member States. 34 00:02:13,867 --> 00:02:18,771 Finally, as of 31st of January last year, 2022, 35 00:02:19,873 --> 00:02:23,243 we had a new Clinical Trial Regulation 36 00:02:23,309 --> 00:02:26,179 that enter into application with the goal 37 00:02:26,246 --> 00:02:28,648 of harmonizing clinical trial submission, 38 00:02:28,715 --> 00:02:33,219 authorization, and supervision across the 27 E.U. member 39 00:02:33,286 --> 00:02:37,924 states as well as Norway, Iceland, and Liechtenstein. 40 00:02:43,696 --> 00:02:45,565 There are three main pillars 41 00:02:45,632 --> 00:02:47,500 of the Clinical Trial Regulation. 42 00:02:48,268 --> 00:02:51,604 And these are, harmonization of clinical trial process, 43 00:02:51,671 --> 00:02:54,641 transparency of clinical trials data, 44 00:02:54,707 --> 00:02:57,777 and safety and protection of trial participants. 45 00:02:59,546 --> 00:03:02,715 These regulations streamline regulatory process 46 00:03:02,782 --> 00:03:05,518 throughout the lifecycle of a clinical trials 47 00:03:06,052 --> 00:03:09,522 and makes it much easier for clinical trial sponsors 48 00:03:09,589 --> 00:03:12,325 to run large multinational trials 49 00:03:12,392 --> 00:03:14,594 in a number of E.U. member states. 50 00:03:15,895 --> 00:03:18,097 Prior to the Clinical Trial Regulation, 51 00:03:18,164 --> 00:03:20,400 and as I show it in my previous slide, 52 00:03:20,934 --> 00:03:24,571 sponsors had to submit clinical trial applications 53 00:03:24,637 --> 00:03:28,741 separately to each Member State of the E.U. 54 00:03:29,342 --> 00:03:33,680 And within each Member State, they had to submit separate 55 00:03:34,447 --> 00:03:36,649 to national competent authorities 56 00:03:36,716 --> 00:03:41,421 and ethics committees. Now, sponsors can submit 57 00:03:41,487 --> 00:03:43,856 a single clinical trial application, 58 00:03:43,923 --> 00:03:46,192 which covers regulatory and ethics 59 00:03:46,259 --> 00:03:48,261 approval for the clinical trial, 60 00:03:49,195 --> 00:03:51,698 greatly reducing the administrative burden 61 00:03:51,764 --> 00:03:53,866 to initiate clinical trial 62 00:03:53,933 --> 00:03:56,936 in a number of E.U. member states. 63 00:03:58,404 --> 00:04:01,107 This new harmonization approach makes it easier 64 00:04:01,174 --> 00:04:04,944 for clinical trial sponsors to collaborate across borders. 65 00:04:05,645 --> 00:04:07,814 Meaning that academic researchers, 66 00:04:07,880 --> 00:04:10,283 for instance, in different countries, 67 00:04:10,350 --> 00:04:13,152 can work together on the same clinical trial. 68 00:04:13,820 --> 00:04:17,924 Or as we can see, more and more consortia 69 00:04:17,991 --> 00:04:21,260 of academic researchers and pharmaceutical companies 70 00:04:22,095 --> 00:04:26,399 can work together easily to combine innovations 71 00:04:26,466 --> 00:04:28,668 in the research and commercial sectors. 72 00:04:30,403 --> 00:04:33,373 Enabling large multinational clinical trials 73 00:04:33,439 --> 00:04:36,142 is a key focus for the European regulators. 74 00:04:36,809 --> 00:04:39,946 By helping sponsors, including academic sponsors, 75 00:04:40,013 --> 00:04:42,682 to run bigger, better clinical trials, 76 00:04:43,316 --> 00:04:45,852 the European medicines regulatory network 77 00:04:45,918 --> 00:04:50,523 aims to support the delivery of high-quality clinical evidence. 78 00:04:52,792 --> 00:04:56,763 The regulation also introduced clear and maximum timelines 79 00:04:56,829 --> 00:04:58,998 for clinical trial assessment, 80 00:04:59,065 --> 00:05:03,336 bringing pre-visibility on the process to the sponsors 81 00:05:03,403 --> 00:05:06,539 and to the patients and healthcare professionals 82 00:05:06,606 --> 00:05:11,344 that would like to enroll subjects in clinical trials. 83 00:05:12,612 --> 00:05:14,714 Collaborative assessment by Member States, 84 00:05:14,781 --> 00:05:18,251 it's also of benefit for all stakeholders involved. 85 00:05:20,787 --> 00:05:23,423 Another pillar of the Clinical Trial Regulation, 86 00:05:23,489 --> 00:05:25,792 as I mentioned before, is transparency. 87 00:05:26,793 --> 00:05:30,596 Clinical trial data throughout the life-cycle of the trial 88 00:05:30,663 --> 00:05:32,965 will be available in the public domain. 89 00:05:34,367 --> 00:05:36,803 Publication of clinical trial applications, 90 00:05:36,869 --> 00:05:40,006 assessment reports, clinical trial modifications, 91 00:05:40,073 --> 00:05:43,242 supervision activities, summary of results 92 00:05:43,309 --> 00:05:46,112 for laypersons will be made available. 93 00:05:47,213 --> 00:05:50,416 These empowers patients and the healthcare professionals 94 00:05:50,483 --> 00:05:53,519 to find recruiting trials and enabling research. 95 00:05:54,187 --> 00:05:57,256 It also increased trust and public support scrutiny. 96 00:05:58,524 --> 00:06:00,493 Finally, the other pillar, 97 00:06:00,560 --> 00:06:03,563 it's safety and protection of trial participants. 98 00:06:04,564 --> 00:06:07,567 With regards to safety, there is also a single process 99 00:06:07,633 --> 00:06:10,069 of submission and safety cooperation 100 00:06:10,136 --> 00:06:12,305 in assessment by Member States. 101 00:06:13,272 --> 00:06:16,209 Finally, in terms of patient protection, 102 00:06:16,275 --> 00:06:19,612 there are specific rules for informed consent 103 00:06:19,679 --> 00:06:23,850 for incapacitated subjects, clinical trials in minors, 104 00:06:23,916 --> 00:06:26,385 clinical trials in pregnancy and breastfeeding, 105 00:06:26,886 --> 00:06:29,322 clinical trials in emerging situations, 106 00:06:29,822 --> 00:06:32,725 and informed consent in cluster trials. 107 00:06:41,534 --> 00:06:44,504 What is in scope of this Clinical Trials Regulation? 108 00:06:45,905 --> 00:06:48,608 The Clinical Trial Regulation applies to interventional 109 00:06:48,674 --> 00:06:51,444 clinical trials with human medicinal products. 110 00:06:52,378 --> 00:06:55,982 And it also introduced a new category of clinical trials, 111 00:06:56,048 --> 00:06:59,185 the so-called low-intervention clinical trials. 112 00:07:00,153 --> 00:07:02,688 What is a low-intervention clinical trial? 113 00:07:03,422 --> 00:07:04,957 A low-intervention clinical trial 114 00:07:05,024 --> 00:07:07,927 means that the investigational medicinal products 115 00:07:07,994 --> 00:07:09,829 are authorized. 116 00:07:09,896 --> 00:07:12,799 The IMP is going to be used in accordance 117 00:07:12,865 --> 00:07:15,134 with the terms of the marketing authorization, 118 00:07:15,201 --> 00:07:19,071 or its use is supported by published scientific evidence 119 00:07:19,138 --> 00:07:20,740 on safety and efficacy. 120 00:07:21,741 --> 00:07:25,344 And there is only minimal additional risk or burden 121 00:07:25,411 --> 00:07:28,815 to the safety of the subjects compared to normal practice. 122 00:07:29,816 --> 00:07:32,084 These low-interventional clinical trials 123 00:07:32,151 --> 00:07:35,588 also link to the risk-based approach introduced 124 00:07:35,655 --> 00:07:37,323 in this Clinical Trial Regulation. 125 00:07:38,858 --> 00:07:40,393 What does it mean? 126 00:07:40,459 --> 00:07:43,529 It means that there will be less stringent rules 127 00:07:43,596 --> 00:07:45,765 applying to those trials conducted 128 00:07:45,832 --> 00:07:47,400 with authorizing medicines 129 00:07:47,466 --> 00:07:51,103 and which pose minimal risk compared to clinical practice. 130 00:07:51,771 --> 00:07:55,842 For example, these risk-based approach will apply 131 00:07:55,908 --> 00:07:59,045 in terms of simplified means for informed consent. 132 00:08:00,746 --> 00:08:03,082 With regards to monitoring of the clinical trial 133 00:08:03,149 --> 00:08:04,851 by the sponsor, it -- 134 00:08:04,917 --> 00:08:08,888 the legislation clearly says that the monitoring will be -- 135 00:08:08,955 --> 00:08:11,457 the extent and nature of the monitoring 136 00:08:11,524 --> 00:08:14,727 will be proportional to the type of trial. 137 00:08:16,095 --> 00:08:19,732 And there are also specific provisions for -- 138 00:08:20,499 --> 00:08:23,069 in terms of damage compensation. 139 00:08:29,575 --> 00:08:32,044 What is not in scope of this regulation? 140 00:08:32,879 --> 00:08:34,247 Non-interventional trials. 141 00:08:34,313 --> 00:08:37,083 So, observational studies are not within the scope 142 00:08:37,149 --> 00:08:38,584 of the regulation, 143 00:08:38,651 --> 00:08:41,687 as well as trials without medicinal products. 144 00:08:43,055 --> 00:08:46,292 For instance, trials only for devices. 145 00:08:53,432 --> 00:08:57,637 I'll give you now a brief overview of how does it work 146 00:08:57,703 --> 00:08:59,605 and the procedure itself for authorization 147 00:08:59,672 --> 00:09:01,274 of a clinical trial 148 00:09:02,508 --> 00:09:05,144 according to the new Clinical Trial Regulation. 149 00:09:07,847 --> 00:09:12,818 The sponsor will submit a clinical trial application 150 00:09:12,885 --> 00:09:17,590 through the so-called Clinical Trials Information System. 151 00:09:18,324 --> 00:09:20,426 This Clinical Trials Information System, 152 00:09:20,493 --> 00:09:25,164 it's the IT tool that supports the whole process foreseen 153 00:09:25,231 --> 00:09:27,333 by the Clinical Trial Regulation 154 00:09:27,400 --> 00:09:31,137 throughout the full lifecycle of the clinical trial. 155 00:09:32,638 --> 00:09:34,573 This system is accessible to national 156 00:09:34,640 --> 00:09:37,743 competent authorities and ethics committees. 157 00:09:38,511 --> 00:09:41,781 And the access from national competent authorities 158 00:09:41,847 --> 00:09:45,084 and ethics committees, is regulated nationally. 159 00:09:46,953 --> 00:09:50,356 There is a new Clinical Trial Application dossier content. 160 00:09:50,423 --> 00:09:53,125 And it's structured on Part I and Part II. 161 00:09:53,893 --> 00:09:56,095 And there is a harmonized dossier content, 162 00:09:56,162 --> 00:09:59,098 meaning when the sponsor submits, 163 00:09:59,165 --> 00:10:03,469 he submits only once through this portal -- 164 00:10:03,536 --> 00:10:05,404 through the IT portal. 165 00:10:05,471 --> 00:10:08,441 And the submission -- the content of the submission 166 00:10:08,507 --> 00:10:10,843 needs to fulfill the requirements 167 00:10:10,910 --> 00:10:13,612 of Annex I of the Clinical Trial Regulation, 168 00:10:13,679 --> 00:10:17,316 which clearly describes all the information 169 00:10:17,383 --> 00:10:19,185 that needs to be submitted 170 00:10:19,251 --> 00:10:22,254 as part of a clinical trial application dossier. 171 00:10:28,294 --> 00:10:31,230 One of the big advantages of the Clinical Trial Regulation 172 00:10:31,297 --> 00:10:35,001 is that it introduced clear timelines for the evaluation 173 00:10:35,067 --> 00:10:38,104 process of a clinical trial application 174 00:10:38,637 --> 00:10:41,107 and after authorization for any process 175 00:10:41,173 --> 00:10:43,109 during the trial life-cycle. 176 00:10:44,877 --> 00:10:47,179 The assessment of a clinical trial application 177 00:10:47,246 --> 00:10:49,281 and supervision of a clinical trial 178 00:10:49,348 --> 00:10:52,084 are responsibilities of the Member States concerned, 179 00:10:52,785 --> 00:10:54,987 including national competent authorities 180 00:10:55,054 --> 00:10:56,655 and ethics committees. 181 00:10:57,390 --> 00:11:00,159 The role and composition of the ethics committees 182 00:11:00,226 --> 00:11:03,562 in the assessment process of the so-called Part 183 00:11:03,629 --> 00:11:07,233 I and Part II, remains a national decision. 184 00:11:07,299 --> 00:11:12,038 However, the regulation is clear that at least one layperson 185 00:11:12,104 --> 00:11:14,240 shall participate in the assessment 186 00:11:14,306 --> 00:11:16,575 of a clinical trial application dossier. 187 00:11:23,416 --> 00:11:26,552 There is a separate assessment for each part, 188 00:11:26,619 --> 00:11:29,388 Part I and Part II, with a final conclusion 189 00:11:29,455 --> 00:11:31,424 and corresponding assessment report. 190 00:11:32,758 --> 00:11:36,262 The assessment report Part I, is issued by the so-called 191 00:11:36,328 --> 00:11:39,899 reporting Member State, meaning the Member State 192 00:11:39,965 --> 00:11:42,001 that takes the lead on the assessment. 193 00:11:42,868 --> 00:11:45,604 And assessment report Part II is issued 194 00:11:45,671 --> 00:11:49,208 by each of the Member States concerned by the trial. 195 00:11:51,110 --> 00:11:53,412 There is a coordinated assessment between 196 00:11:53,479 --> 00:11:55,815 the reporting Member State and the Member States 197 00:11:55,881 --> 00:11:58,217 concerned for Part I of the dossier. 198 00:11:59,085 --> 00:12:01,120 And this is also a big benefit 199 00:12:01,187 --> 00:12:03,089 of the Clinical Trial Regulation. 200 00:12:03,589 --> 00:12:06,325 The Member States collaborate in the assessment 201 00:12:06,392 --> 00:12:10,429 making a much better use of available resources in the E.U. 202 00:12:11,997 --> 00:12:14,733 The reporting Member State takes a leading role 203 00:12:14,800 --> 00:12:17,036 in drafting an assessment report 204 00:12:17,103 --> 00:12:19,305 with input from the Member States concerned. 205 00:12:20,606 --> 00:12:23,409 Each Member State concerned, produce the assessment report 206 00:12:23,476 --> 00:12:25,744 for the Part II of their concern. 207 00:12:27,079 --> 00:12:30,015 And then based on the conclusions on Part I 208 00:12:30,082 --> 00:12:31,317 and Part II, 209 00:12:31,383 --> 00:12:34,954 each Member State concerned will individually issue 210 00:12:35,020 --> 00:12:37,356 a single decision on the authorization 211 00:12:37,423 --> 00:12:39,391 of the clinical trial application. 212 00:12:40,025 --> 00:12:42,228 And what I meant by a single decision, 213 00:12:42,294 --> 00:12:45,965 so each Member State concerned will need to issue a decision. 214 00:12:46,031 --> 00:12:50,569 But conversely to what happened before, the Member State -- 215 00:12:50,636 --> 00:12:53,806 each Member State only issues one decision. 216 00:12:53,873 --> 00:12:55,141 That is a common decision 217 00:12:55,207 --> 00:12:57,476 between the national competent authority 218 00:12:57,543 --> 00:12:59,378 and the ethics committee. 219 00:12:59,445 --> 00:13:02,648 While before it used to be two decisions, 220 00:13:02,715 --> 00:13:05,151 one coming from the national competent authority 221 00:13:05,217 --> 00:13:07,319 and the other from the ethics committee. 222 00:13:09,088 --> 00:13:12,525 Off note, a single decision per Member State concerned 223 00:13:12,591 --> 00:13:16,996 can be tacit and based only on Part I conclusions. 224 00:13:17,663 --> 00:13:19,031 What does it mean? 225 00:13:19,098 --> 00:13:22,401 What does it mean is that where the Member State concerned 226 00:13:22,968 --> 00:13:27,072 does not notify the sponsor within the legal timelines 227 00:13:27,706 --> 00:13:30,276 of its decision in that Member State, 228 00:13:30,910 --> 00:13:34,513 then the conclusion of the assessment of Part 229 00:13:34,580 --> 00:13:37,983 I becomes the final conclusion for that Member State. 230 00:13:38,584 --> 00:13:41,720 And this is what we call then the tacit approval. 231 00:13:44,156 --> 00:13:47,993 This slide summarizes the overall procedure and timeline 232 00:13:48,060 --> 00:13:50,095 for the assessment of clinical trial. 233 00:13:51,163 --> 00:13:53,599 And it just illustrates what I have mentioned 234 00:13:53,666 --> 00:13:55,267 in previous slides. 235 00:13:56,402 --> 00:13:59,838 When a sponsor wants to get approval of 236 00:13:59,905 --> 00:14:05,377 a clinical trial in E.U., it'll submit a single submission 237 00:14:05,444 --> 00:14:09,682 through this IT system, the so-called E.U. portal. 238 00:14:11,417 --> 00:14:15,688 And it can be just a submission for -- 239 00:14:15,754 --> 00:14:18,157 to run the trial in one Member State 240 00:14:18,224 --> 00:14:20,826 or it can be a submission to run the trial 241 00:14:20,893 --> 00:14:23,329 in all 27 Member States 242 00:14:23,395 --> 00:14:27,466 plus Norway, Iceland, and Liechtenstein. 243 00:14:27,533 --> 00:14:30,202 So, it can be any variation of those. 244 00:14:30,803 --> 00:14:34,106 The process is always the same, submission through the portal. 245 00:14:35,474 --> 00:14:38,010 When the sponsor submits through the portal, 246 00:14:38,077 --> 00:14:42,414 needs to indicate which Member State the sponsor 247 00:14:42,481 --> 00:14:46,018 is proposing for reporting Member State. 248 00:14:46,085 --> 00:14:48,420 Meaning the Member State taking the lead 249 00:14:48,487 --> 00:14:51,257 on the assessment of Part I of the dossier. 250 00:14:53,559 --> 00:14:59,665 Within three days of the submission of the dossier, it -- 251 00:14:59,732 --> 00:15:03,569 the Member State concerned by the submission -- 252 00:15:03,636 --> 00:15:07,673 by the trial, needs to say if they are interested 253 00:15:07,740 --> 00:15:10,242 to be reporting Member State or not. 254 00:15:11,343 --> 00:15:14,713 And the proposed reporting Member State by the sponsor, 255 00:15:15,414 --> 00:15:19,351 needs to say, if -- in case they are not interested. 256 00:15:21,287 --> 00:15:23,422 If only one Member State 257 00:15:23,489 --> 00:15:26,492 is willing to become the reporting Member State, 258 00:15:26,558 --> 00:15:30,062 then this Member State will become reporting Member State. 259 00:15:30,129 --> 00:15:33,399 However, if there is more than one Member State 260 00:15:33,465 --> 00:15:35,401 with an interest to become reporting 261 00:15:35,467 --> 00:15:37,403 Member State, there is need -- 262 00:15:37,469 --> 00:15:41,774 there is a process in place to agree on which 263 00:15:41,840 --> 00:15:44,843 Member State will take the reporting Member State. 264 00:15:46,945 --> 00:15:51,383 In case there is no agreement reached amongst the concerned 265 00:15:51,450 --> 00:15:53,118 Member States by the trial, 266 00:15:53,986 --> 00:15:56,955 then the proposal from the company 267 00:15:57,022 --> 00:16:02,628 will become the one valid. Meaning the reporting 268 00:16:02,695 --> 00:16:06,398 Member State proposed by the company will be the one 269 00:16:06,465 --> 00:16:09,234 that will become effectively the reporting 270 00:16:09,301 --> 00:16:10,903 Member State. 271 00:16:11,704 --> 00:16:13,238 Once decided on the reporting 272 00:16:13,305 --> 00:16:17,943 Member State, then there is a validation that takes place. 273 00:16:18,510 --> 00:16:20,279 And this validation basically, 274 00:16:20,346 --> 00:16:24,183 it's just to check if the clinical trial falls 275 00:16:24,249 --> 00:16:26,218 within the scope of the regulation, 276 00:16:26,885 --> 00:16:31,223 if the dossier is complete and in accordance with Annex 277 00:16:31,290 --> 00:16:35,127 I of the regulation. Meaning if all documents 278 00:16:35,194 --> 00:16:37,029 foreseen by the regulation are there. 279 00:16:37,896 --> 00:16:39,865 And if this is not the case, 280 00:16:40,632 --> 00:16:43,435 there will be an opportunity for 10 more days. 281 00:16:43,502 --> 00:16:46,872 So, the reporting Member State will feed back to the sponsor 282 00:16:47,439 --> 00:16:51,243 and the sponsor will have 10 more days 283 00:16:51,310 --> 00:16:55,681 to comment or supplement with any information necessary. 284 00:16:56,281 --> 00:16:59,318 And all of these happens through the portal. 285 00:16:59,385 --> 00:17:02,588 So, it's -- everything is done through the IT system. 286 00:17:04,723 --> 00:17:10,396 Once the dossier is validated, then the assessment part starts. 287 00:17:11,330 --> 00:17:14,466 We have, in one side, the so-called Part 288 00:17:14,533 --> 00:17:17,403 I of the dossier that you can see in the slide. 289 00:17:17,469 --> 00:17:20,472 It includes; the protocol and study design; 290 00:17:21,006 --> 00:17:25,878 it includes the justification from the sponsor in case 291 00:17:25,944 --> 00:17:28,147 it's a low-interventional clinical trial; 292 00:17:28,814 --> 00:17:31,216 all the manufacturing and importation documents 293 00:17:31,283 --> 00:17:32,885 for the IMP; 294 00:17:33,652 --> 00:17:36,588 the investigation medicinal product dossier; 295 00:17:36,655 --> 00:17:38,257 the investigator's brochure. 296 00:17:39,024 --> 00:17:42,594 And in case the sponsor has previously asked 297 00:17:42,661 --> 00:17:45,831 for scientific advice or if the sponsor 298 00:17:45,898 --> 00:17:48,901 has a pediatric investigation plan approved, 299 00:17:48,967 --> 00:17:51,570 it needs also to include it here. 300 00:17:52,604 --> 00:17:55,941 And this part will also look at the labelling of the IMP. 301 00:17:57,075 --> 00:18:00,078 So, all these aspects will be looked through 302 00:18:00,145 --> 00:18:01,847 a coordinated assessment 303 00:18:01,914 --> 00:18:05,017 between all Member States concerned by the trial, 304 00:18:05,818 --> 00:18:07,619 with reporting Member States 305 00:18:07,686 --> 00:18:09,521 taking the lead on the assessment. 306 00:18:10,155 --> 00:18:14,026 So, the reporting Member State will have initially 26 days 307 00:18:14,092 --> 00:18:16,428 to produce a draft assessment report, 308 00:18:17,129 --> 00:18:18,864 or an initial assessment report, 309 00:18:19,498 --> 00:18:22,935 that then will be circulated to all Member States concerned, 310 00:18:24,102 --> 00:18:30,142 which have 12 days to comment on this draft assessment report. 311 00:18:30,776 --> 00:18:33,812 And further to that, the reporting Member State 312 00:18:33,879 --> 00:18:35,881 has an additional seven days 313 00:18:36,415 --> 00:18:38,851 to finalize and incorporate comments, 314 00:18:38,917 --> 00:18:41,220 receive it from the Member States concerned. 315 00:18:42,621 --> 00:18:50,529 In total, we have 45 days of evaluation timeline for a trial. 316 00:18:51,563 --> 00:18:55,367 In case there are questions at the end of these 45 days, 317 00:18:55,434 --> 00:18:58,070 and there are issues that need clarification, 318 00:18:58,136 --> 00:19:01,540 a list of questions will be sent to the sponsor 319 00:19:02,174 --> 00:19:04,676 and a maximum of 31 days 320 00:19:04,743 --> 00:19:09,314 plus will be allowed to complete the assessment of the trial. 321 00:19:10,616 --> 00:19:13,986 At the same time, we are having this coordinated assessment, 322 00:19:14,052 --> 00:19:15,521 each Member State concerned 323 00:19:15,587 --> 00:19:19,725 will have the national evaluation of Part II. 324 00:19:19,791 --> 00:19:21,527 And what is in Part II? 325 00:19:22,127 --> 00:19:25,397 Part II it's; informed consent; subject recruitment; 326 00:19:25,464 --> 00:19:28,567 data protection; rewards, compensation; 327 00:19:29,935 --> 00:19:33,305 suitability of investigators and of trial sites; 328 00:19:33,372 --> 00:19:34,706 damage compensation; 329 00:19:34,773 --> 00:19:38,243 and collection storage and use of biological samples. 330 00:19:38,310 --> 00:19:42,714 So, these will be assessed by each Member State concerned. 331 00:19:45,017 --> 00:19:48,387 After this assessment period 332 00:19:49,154 --> 00:19:55,527 and once we have finalized assessment of Part I, 333 00:19:56,929 --> 00:20:01,867 then each Member State concerned should notify the sponsor 334 00:20:01,934 --> 00:20:05,837 through the E.U. portal whether the trial is authorized, 335 00:20:06,438 --> 00:20:09,575 authorized subject to conditions, or refused. 336 00:20:11,109 --> 00:20:14,046 If the reporting Member States considers 337 00:20:14,112 --> 00:20:17,049 that Part I of the dossier is acceptable, 338 00:20:18,116 --> 00:20:23,255 then the Member States concerned should consider it acceptable 339 00:20:24,089 --> 00:20:26,358 with very few exceptions. 340 00:20:26,425 --> 00:20:31,263 And these exceptions will be that the participation -- 341 00:20:31,330 --> 00:20:33,065 the Member State concern considers 342 00:20:33,131 --> 00:20:35,133 that participation in the trial 343 00:20:35,200 --> 00:20:39,871 will lead to a subject receiving an inferior treatment 344 00:20:39,938 --> 00:20:43,642 than in normal clinical practice in that E.U. member state. 345 00:20:44,543 --> 00:20:48,947 Or that the trial is infringing national laws 346 00:20:49,014 --> 00:20:51,083 or there are specific considerations 347 00:20:51,149 --> 00:20:54,686 regarding subject safety and data reliability. 348 00:20:57,456 --> 00:21:01,793 Overall, a trial can be refused if a Member State 349 00:21:01,860 --> 00:21:06,064 concerned disagrees with Part I, as I just explained. 350 00:21:06,665 --> 00:21:09,901 Or if there are aspects of Part II 351 00:21:09,968 --> 00:21:11,903 that are not complied with. 352 00:21:14,072 --> 00:21:18,176 Each Member State concerned needs to put its decision 353 00:21:18,243 --> 00:21:20,412 in the system through the E.U. portal 354 00:21:20,479 --> 00:21:25,584 within five days of the reporting Member State 355 00:21:25,651 --> 00:21:27,719 finalizing its assessment. 356 00:21:28,654 --> 00:21:29,921 As I mentioned before, 357 00:21:29,988 --> 00:21:35,127 a single decision coming from national competent authority 358 00:21:35,193 --> 00:21:39,564 and ethics committee is issued by each Member State concerned. 359 00:21:41,366 --> 00:21:46,605 Just of note, the authorization of the trial can expire. 360 00:21:46,672 --> 00:21:49,041 And this is also a new feature introduced 361 00:21:49,107 --> 00:21:50,776 by the Clinical Trial Regulation. 362 00:21:52,344 --> 00:21:56,648 If no subject has been included in a trial in a Member State 363 00:21:56,715 --> 00:22:00,252 concerned within two years of the authorization, 364 00:22:00,752 --> 00:22:03,789 then the authorization of that trial 365 00:22:03,855 --> 00:22:08,360 in that concerned Member State will be considered expired. 366 00:22:15,367 --> 00:22:17,903 Linked to the Clinical Trial Regulation, 367 00:22:17,969 --> 00:22:22,874 there have been also two delegated acts adopted. 368 00:22:24,710 --> 00:22:29,548 And delegated acts are -- in fact, it's regulations 369 00:22:29,614 --> 00:22:34,619 that are published and adopted to further clarify 370 00:22:34,686 --> 00:22:38,990 certain aspects of the initial regulation, 371 00:22:39,057 --> 00:22:43,261 more on a practical aspect of it. 372 00:22:44,029 --> 00:22:46,164 So, from the Clinical Trial Regulation, 373 00:22:46,231 --> 00:22:49,835 we have two delegated acts that have been adopted. 374 00:22:50,502 --> 00:22:53,004 One is regarding aspects 375 00:22:53,071 --> 00:22:56,341 of good clinical practice inspection procedures. 376 00:22:57,309 --> 00:23:00,145 And it covers; GCP inspectors training; 377 00:23:00,212 --> 00:23:02,547 qualification; impartiality; 378 00:23:02,614 --> 00:23:06,418 Member States quality system for GCP inspections; 379 00:23:06,985 --> 00:23:08,286 Member States procedures for 380 00:23:08,353 --> 00:23:11,990 GCP inspections; inspections records and reports. 381 00:23:13,125 --> 00:23:15,026 Just off note, inspection reports 382 00:23:15,093 --> 00:23:17,329 prepared by the E.U. inspectors 383 00:23:17,395 --> 00:23:19,798 need to be submitted through the Clinical 384 00:23:19,865 --> 00:23:23,268 Trials Information System as foreseen in Article 385 00:23:23,335 --> 00:23:26,404 78 of the Clinical Trial Regulation. 386 00:23:30,609 --> 00:23:34,079 The other delegated act that has been adopted, 387 00:23:34,146 --> 00:23:36,047 it's the one regarding the rules 388 00:23:36,114 --> 00:23:39,184 and procedures for cooperation of the Member States 389 00:23:39,251 --> 00:23:41,753 in safety assessment of clinical trials. 390 00:23:42,554 --> 00:23:45,557 And this delegated act covers the cooperation 391 00:23:45,624 --> 00:23:49,461 between Member States in the assessment of information 392 00:23:49,528 --> 00:23:51,997 and reports submitted under Article 393 00:23:52,063 --> 00:23:55,934 42 and Article 43 of the Clinical 394 00:23:56,001 --> 00:23:57,602 Trial Regulation. 395 00:23:58,703 --> 00:24:01,840 In this act, it's also defined as safety assessing 396 00:24:01,907 --> 00:24:04,376 Member State for each active substance 397 00:24:04,442 --> 00:24:07,579 used in investigational medicinal products. 398 00:24:13,618 --> 00:24:16,087 There is a transition period for the Clinical 399 00:24:16,154 --> 00:24:17,656 Trial Regulation. 400 00:24:17,722 --> 00:24:20,759 So, this is a three-year transition period 401 00:24:20,826 --> 00:24:23,595 to the Clinical Trials Information System. 402 00:24:24,996 --> 00:24:27,632 As I mentioned before, the Clinical Trial Regulation 403 00:24:27,699 --> 00:24:31,937 became applicable as of 31st of January, 2022. 404 00:24:33,205 --> 00:24:37,642 Between this date and 31st of January this year, 405 00:24:38,643 --> 00:24:42,447 sponsors could choose if they were submitting 406 00:24:42,514 --> 00:24:46,918 the clinical trial application through the old legislation, 407 00:24:46,985 --> 00:24:51,056 or if they would submit according to the new regulation 408 00:24:51,122 --> 00:24:53,525 and using the new IT system. 409 00:24:54,392 --> 00:24:59,531 So, it was optional. As of 31st of January this year, 410 00:25:00,265 --> 00:25:04,502 any new clinical trial to be conducted in the European Union 411 00:25:04,569 --> 00:25:07,505 needs to be in accordance to the new Clinical 412 00:25:07,572 --> 00:25:11,042 Trial Regulation and submitted through the Clinical 413 00:25:11,109 --> 00:25:12,711 Trials Information System. 414 00:25:13,945 --> 00:25:18,950 Between January this year and 31st of January, 2025, 415 00:25:19,684 --> 00:25:21,820 we have two years transition 416 00:25:21,887 --> 00:25:25,957 for the trials that were already ongoing before the Clinical 417 00:25:26,024 --> 00:25:27,792 Trial Regulation became applicable. 418 00:25:28,693 --> 00:25:34,399 As of 31st of January, 2025, all ongoing clinical trials 419 00:25:34,466 --> 00:25:36,902 must be transferred to the Clinical 420 00:25:36,968 --> 00:25:39,204 Trials Information System. 421 00:25:42,173 --> 00:25:44,075 To give you a little bit more information 422 00:25:44,142 --> 00:25:46,945 about these Clinical Trials Information System. 423 00:25:48,146 --> 00:25:50,849 This system is made of the so-called E.U. 424 00:25:50,916 --> 00:25:53,885 portal and E.U. database. 425 00:25:55,954 --> 00:25:58,857 As I mentioned before, everything that happens 426 00:25:58,924 --> 00:26:01,626 during the life-cycle of a clinical trial 427 00:26:01,693 --> 00:26:04,429 will be submitted through the E.U. portal. 428 00:26:04,496 --> 00:26:09,034 And every document will then be stored in the E.U. database 429 00:26:09,634 --> 00:26:11,603 as mentioned in Articles 80 430 00:26:11,670 --> 00:26:14,306 and 81 of the Clinical Trial Regulation. 431 00:26:16,541 --> 00:26:19,611 This system allows sponsors for -- 432 00:26:19,678 --> 00:26:24,282 to apply for a clinical trial in up to 30 E.U./EEA countries 433 00:26:24,349 --> 00:26:27,452 with a single application as illustrated before. 434 00:26:28,553 --> 00:26:31,456 Facilitate involvement of trial participants 435 00:26:31,523 --> 00:26:33,992 by allowing easy expansion of trials 436 00:26:34,059 --> 00:26:36,594 to other E.U./EEA countries. 437 00:26:36,661 --> 00:26:40,865 Meaning if a sponsor submitted initially 438 00:26:41,967 --> 00:26:43,902 a clinical trial application 439 00:26:43,969 --> 00:26:48,006 to run the trial in five member states 440 00:26:48,073 --> 00:26:51,042 and then decides they want to add two or three, 441 00:26:51,609 --> 00:26:53,778 there is a specific procedure for that 442 00:26:53,845 --> 00:26:57,882 and it's a much simpler procedure 443 00:26:57,949 --> 00:27:00,418 that is done again through this system. 444 00:27:02,387 --> 00:27:05,523 It also facilitates collaboration across borders. 445 00:27:06,825 --> 00:27:09,995 And at the end, ensures that E.U. and EEA 446 00:27:10,061 --> 00:27:14,532 remain an attractive location for clinical research investment 447 00:27:14,599 --> 00:27:17,702 because the procedures have been greatly simplified 448 00:27:17,769 --> 00:27:20,905 compared to the past legislation. 449 00:27:21,973 --> 00:27:24,209 The Clinical Trials Information System 450 00:27:24,275 --> 00:27:26,778 also allows the fulfillment 451 00:27:26,845 --> 00:27:29,714 of all clinical trial publication requirements 452 00:27:30,315 --> 00:27:32,017 with no additional effort. 453 00:27:32,817 --> 00:27:35,987 Because all documents that are submitted through the portal, 454 00:27:36,054 --> 00:27:38,323 will be stored in the E.U. database. 455 00:27:38,857 --> 00:27:41,659 And the majority of the documents in the database 456 00:27:41,726 --> 00:27:43,595 will then be -- 457 00:27:43,661 --> 00:27:45,897 become available in the public domain. 458 00:27:46,631 --> 00:27:51,069 It's a question of time and type of document. 459 00:27:51,136 --> 00:27:54,973 And we'll speak about that later on, on this presentation. 460 00:28:02,414 --> 00:28:05,717 The Clinical Trials Information System is -- 461 00:28:05,784 --> 00:28:10,388 consists of a public website and two secure domains. 462 00:28:11,756 --> 00:28:15,160 The public website, everyone can search for information 463 00:28:15,226 --> 00:28:16,928 on clinical trials -- 464 00:28:16,995 --> 00:28:20,165 ongoing clinical trials, any other information. 465 00:28:20,231 --> 00:28:23,134 And I'll show it later on in the presentation. 466 00:28:23,935 --> 00:28:25,937 In addition to the public website, 467 00:28:26,004 --> 00:28:28,706 there is what we call a sponsor workspace 468 00:28:29,374 --> 00:28:32,377 where the clinical trial sponsors and organizations 469 00:28:32,444 --> 00:28:34,679 that work with them, so the CROs, 470 00:28:34,746 --> 00:28:37,816 can apply for and manage a clinical trial. 471 00:28:38,716 --> 00:28:44,055 And then an authority workspace for E.U. member states, 472 00:28:44,122 --> 00:28:45,356 EEA countries, 473 00:28:45,423 --> 00:28:48,393 and the European Commission to assess, authorize, 474 00:28:48,460 --> 00:28:50,662 and oversee clinical trials. 475 00:28:55,700 --> 00:28:57,202 This is a busy slide. 476 00:28:57,268 --> 00:29:03,308 But it just to give you an overview of all the process 477 00:29:03,374 --> 00:29:06,511 that you can do -- all the actions that you can do 478 00:29:06,578 --> 00:29:09,814 in the Clinical Trials Information System. 479 00:29:10,582 --> 00:29:14,119 As you can see, sponsors, they submit initial dossier. 480 00:29:14,185 --> 00:29:15,920 They can update the dossier. 481 00:29:17,322 --> 00:29:21,559 All type of notifications like; withdrawal; start of the trial; 482 00:29:21,626 --> 00:29:24,229 first visit, subject; end of recruitment; 483 00:29:24,295 --> 00:29:29,200 end of trial; submission of clinical studies result summary; 484 00:29:29,267 --> 00:29:32,437 submission of inspection reports in third countries. 485 00:29:32,504 --> 00:29:36,241 All of these for the sponsors is done through the portal. 486 00:29:36,307 --> 00:29:38,676 And then you have also all the actions 487 00:29:38,743 --> 00:29:41,112 that are possible for Member States 488 00:29:41,179 --> 00:29:43,047 and all the other stakeholders 489 00:29:43,114 --> 00:29:46,251 concerned by the Clinical Trial Regulation. 490 00:29:52,323 --> 00:29:56,127 According to Article 81(4) of the Clinical Trial Regulation, 491 00:29:56,694 --> 00:29:59,797 the E.U. database shall be publicly accessible 492 00:30:00,398 --> 00:30:03,134 unless confidentiality is justified. 493 00:30:03,801 --> 00:30:06,237 And this is to protect personal data, 494 00:30:06,304 --> 00:30:08,573 commercial confidential information, 495 00:30:08,640 --> 00:30:11,809 draft assessment reports, supervision activities. 496 00:30:13,545 --> 00:30:15,980 But by default, with these exceptions, 497 00:30:16,047 --> 00:30:20,351 all data submitted will become available in the public domain 498 00:30:20,418 --> 00:30:22,921 at a certain point in time. 499 00:30:25,056 --> 00:30:29,060 The Clinical Trial Information System users like sponsors, 500 00:30:29,127 --> 00:30:31,663 marketing authorization applicants, Member States, 501 00:30:31,729 --> 00:30:33,665 EMA, Commission, 502 00:30:33,731 --> 00:30:36,100 are the so-called joint controllers 503 00:30:36,167 --> 00:30:38,169 for protection of personal data 504 00:30:38,236 --> 00:30:41,906 when using the Clinical Trial Information System. 505 00:30:41,973 --> 00:30:44,309 And this has been established in this 506 00:30:44,375 --> 00:30:47,645 so-called Joint Controllership Arrangement. 507 00:30:50,715 --> 00:30:53,551 Regarding CTIS in the public domain, 508 00:30:53,618 --> 00:30:56,854 you can search for information on clinical trial applications, 509 00:30:56,921 --> 00:30:59,791 information on ongoing and recruiting trials. 510 00:31:00,358 --> 00:31:04,929 And there is also an obligation that has been introduced 511 00:31:04,996 --> 00:31:06,664 by the Clinical Trial Regulation 512 00:31:06,731 --> 00:31:11,836 that the sponsors need to prepare a summary of the results 513 00:31:12,370 --> 00:31:14,872 in lay language for laypersons. 514 00:31:18,843 --> 00:31:22,013 So, just to give you a little bit more information 515 00:31:23,181 --> 00:31:24,816 regarding which data 516 00:31:24,882 --> 00:31:28,219 is published for a specific clinical trial. 517 00:31:29,621 --> 00:31:32,423 Only applications on which a decision has been reached 518 00:31:32,490 --> 00:31:35,126 by the Member State concerned will be made public. 519 00:31:36,461 --> 00:31:39,964 The sponsor will need to provide a summary of results 520 00:31:40,031 --> 00:31:42,867 for laypersons once the trial is finalized. 521 00:31:44,102 --> 00:31:47,805 The default is always to make public at the first opportunity. 522 00:31:47,872 --> 00:31:51,342 However, sponsors have options to defer the timing 523 00:31:51,409 --> 00:31:54,612 of publication of specific data documents. 524 00:31:55,947 --> 00:31:59,817 There has been lots of discussion on what to publish 525 00:31:59,884 --> 00:32:03,254 and not to publish still in compliance 526 00:32:03,321 --> 00:32:05,423 with the Clinical Trial Regulation. 527 00:32:05,490 --> 00:32:08,860 And what has been achieved, tends to be -- 528 00:32:09,427 --> 00:32:12,597 to strike the balance between access to information 529 00:32:12,664 --> 00:32:15,233 and protecting the interest of sponsors. 530 00:32:16,467 --> 00:32:19,470 You can find more information on this document, 531 00:32:19,537 --> 00:32:21,606 the so-called functional specifications 532 00:32:21,673 --> 00:32:23,508 for the E.U. portal and database 533 00:32:23,574 --> 00:32:28,212 to be audited on an appendix on disclosure rules. 534 00:32:28,846 --> 00:32:30,448 Just to give you some examples. 535 00:32:31,549 --> 00:32:36,721 Once a decision on the trial is published -- post on the -- 536 00:32:38,189 --> 00:32:40,658 through the Clinical Trials Information System, 537 00:32:40,725 --> 00:32:43,861 automatically, the date of decision of the -- 538 00:32:43,928 --> 00:32:46,464 on a trial will become publicly available. 539 00:32:47,565 --> 00:32:50,168 The same when there is a notification 540 00:32:50,234 --> 00:32:52,403 on the first visit of first subject, 541 00:32:53,237 --> 00:32:55,673 this will also become immediately available 542 00:32:55,740 --> 00:32:57,508 in the public domain. 543 00:32:57,575 --> 00:32:59,977 The end date of subject recruitment 544 00:33:00,678 --> 00:33:03,681 also becomes available once put in the system. 545 00:33:04,982 --> 00:33:06,684 Dates of temporary out, 546 00:33:06,751 --> 00:33:08,653 main characteristics out of the trial, 547 00:33:08,720 --> 00:33:11,089 this is all information that as soon as it 548 00:33:11,155 --> 00:33:12,824 is submitted through the system, 549 00:33:12,890 --> 00:33:15,026 will become available in the public domain. 550 00:33:16,094 --> 00:33:18,629 Other type of information, for instance, 551 00:33:18,696 --> 00:33:24,569 the protocol of the study will become available by definition 552 00:33:25,370 --> 00:33:28,206 at the time of the decision on the trial, 553 00:33:28,272 --> 00:33:31,242 decision to authorize or refuse the trial. 554 00:33:31,943 --> 00:33:34,512 But here, there are possibilities to defer 555 00:33:34,579 --> 00:33:36,247 because we need to strike the balance 556 00:33:36,314 --> 00:33:39,851 with the commercial confidential information. 557 00:33:40,885 --> 00:33:44,822 For instance, for protocols, it's possible to defer. 558 00:33:44,889 --> 00:33:47,558 If it's a Phase I study or a bio-[inaudible] 559 00:33:47,625 --> 00:33:52,830 study, the sponsor can ask to defer up to seven years 560 00:33:53,831 --> 00:33:55,733 after the authorization of the study. 561 00:33:56,267 --> 00:33:59,470 Or up to the time of the marketing authorization 562 00:33:59,537 --> 00:34:01,205 where the study is used. 563 00:34:02,073 --> 00:34:05,243 For instance, if it's for a Phase II or Phase III study, 564 00:34:05,977 --> 00:34:10,281 the sponsor can ask for the protocol publication 565 00:34:10,348 --> 00:34:14,552 to be deferred up to five years after the end of the trial. 566 00:34:15,920 --> 00:34:20,124 When it comes to the clinical trial results summary 567 00:34:20,191 --> 00:34:23,060 and summary for laypersons, 568 00:34:23,127 --> 00:34:25,763 the sponsor has an obligation to publish 569 00:34:25,830 --> 00:34:29,801 it 12 months after the end of the trial in the E.U. 570 00:34:31,669 --> 00:34:36,140 And in terms of clinical study reports, the sponsor -- 571 00:34:36,207 --> 00:34:38,075 the marketing authorization applicant 572 00:34:38,709 --> 00:34:43,848 will have an obligation to make it available in the system 573 00:34:43,915 --> 00:34:46,951 and to be published 30 days 574 00:34:47,018 --> 00:34:49,987 after marketing authorization decision, 575 00:34:50,054 --> 00:34:54,058 or 30 days after withdrawal of a marketing authorization 576 00:34:54,125 --> 00:34:56,627 application where the study was used. 577 00:34:59,864 --> 00:35:02,266 Which documents will never be published? 578 00:35:02,900 --> 00:35:05,770 All the quality-related information that include; 579 00:35:06,771 --> 00:35:11,509 IMPD quality; quality-related requests for information raised 580 00:35:11,576 --> 00:35:14,812 during the assessment; quality assessment reports; 581 00:35:15,513 --> 00:35:17,715 any draft assessment reports; 582 00:35:17,782 --> 00:35:20,451 any documents versions not for publication 583 00:35:20,518 --> 00:35:22,019 containing personal data 584 00:35:22,086 --> 00:35:24,155 or commercial confidential information; 585 00:35:24,722 --> 00:35:26,824 and financial agreements between the sponsor 586 00:35:26,891 --> 00:35:29,794 and the investigator site will never be published. 587 00:35:33,698 --> 00:35:36,601 To finalize this lecture, I would like to provide you 588 00:35:36,667 --> 00:35:39,904 with some information on an ongoing E.U. 589 00:35:39,971 --> 00:35:44,208 initiative to transform the E.U. clinical research environment, 590 00:35:44,742 --> 00:35:48,746 the so-called Accelerating Clinical Trials in the E.U. 591 00:35:50,548 --> 00:35:55,319 Since 2022, the E.U. is building on the momentum 592 00:35:55,386 --> 00:35:57,889 generated by the Clinical Trial Regulation 593 00:35:57,955 --> 00:36:00,458 and the Clinical Trials Information System 594 00:36:01,025 --> 00:36:03,995 to transform all clinical trials are initiated, 595 00:36:04,061 --> 00:36:06,030 designed, and run in the E.U. 596 00:36:07,965 --> 00:36:10,201 This transformation is carried out 597 00:36:10,268 --> 00:36:14,105 under this ACT E.U. initiative. 598 00:36:14,972 --> 00:36:18,209 This is a joint initiative of the European Commission, 599 00:36:18,276 --> 00:36:22,013 European Medicines Agency, and Heads of Medicines Agencies 600 00:36:22,613 --> 00:36:25,082 who represent national regulatory authorities 601 00:36:25,149 --> 00:36:30,421 in the E.U. The Accelerating Clinical Trials 602 00:36:30,488 --> 00:36:34,158 initiative includes an ambitious program 603 00:36:34,225 --> 00:36:36,193 of 10 priority actions, 604 00:36:36,694 --> 00:36:40,364 which aim to further strengthen E.U. clinical trials 605 00:36:40,965 --> 00:36:42,433 and to promote the development 606 00:36:42,500 --> 00:36:45,870 of high-quality, safe, and effective medicines. 607 00:36:46,904 --> 00:36:49,540 The priority actions include, for instance, 608 00:36:49,607 --> 00:36:54,478 the modernization of GCP, to adapt GCP inspections methods 609 00:36:54,545 --> 00:36:56,480 to take into account for innovation 610 00:36:56,547 --> 00:36:59,016 in clinical trial tools and processes. 611 00:37:01,352 --> 00:37:04,422 Other area, it's clinical trials methodologies. 612 00:37:04,488 --> 00:37:06,390 For instance, guidance in areas 613 00:37:06,457 --> 00:37:09,860 such as complex and decentralized trials. 614 00:37:15,866 --> 00:37:19,136 This is just an overview of what is foreseen 615 00:37:19,203 --> 00:37:21,739 in terms of actions for the next four years 616 00:37:22,373 --> 00:37:26,744 on these Accelerating Clinical Trials E.U. initiative. 617 00:37:28,112 --> 00:37:30,181 So, ensure effective operation 618 00:37:30,247 --> 00:37:32,116 of the Clinical Trials Regulation. 619 00:37:32,984 --> 00:37:36,053 Simplify governance and align the clinical trials 620 00:37:37,254 --> 00:37:40,925 approval with scientific advice. Support academic sponsors 621 00:37:40,992 --> 00:37:43,027 to conduct impactful clinical trials. 622 00:37:43,094 --> 00:37:45,329 And we have mentioned it during the presentation, 623 00:37:45,396 --> 00:37:49,400 for instance, in the use of multinational trials. 624 00:37:50,635 --> 00:37:53,437 Establish the place of novel methodologies 625 00:37:53,504 --> 00:37:57,541 like decentralized trials. Enable decentralized approach. 626 00:37:58,142 --> 00:38:00,544 Lots of investment in terms of training. 627 00:38:02,146 --> 00:38:05,416 Align internationally in GCP, for instance. 628 00:38:06,117 --> 00:38:08,886 Optimize use of data about clinical trials 629 00:38:08,953 --> 00:38:11,622 for better research and decision making. 630 00:38:11,689 --> 00:38:14,225 And create a multi-stakeholder platform. 631 00:38:14,792 --> 00:38:19,363 And this last one is something that is already ongoing. 632 00:38:19,430 --> 00:38:21,966 And in fact, there will be a meeting this month. 633 00:38:22,600 --> 00:38:24,568 And this multi-stakeholder platform, 634 00:38:24,635 --> 00:38:29,340 it will include representatives from all stakeholders 635 00:38:30,374 --> 00:38:32,476 on the clinical trials area. 636 00:38:32,543 --> 00:38:35,946 Meaning patients, healthcare professionals, academics, 637 00:38:37,915 --> 00:38:41,919 clinical trial investigators, clinical research organizations, 638 00:38:41,986 --> 00:38:45,523 sponsors, ethics committees' representatives. 639 00:38:46,057 --> 00:38:49,527 And they all come together to discuss 640 00:38:50,361 --> 00:38:56,367 how to improve the clinical research environment -- 641 00:38:56,434 --> 00:38:59,670 how to improve the conduct of clinical trials in the E.U. 642 00:39:01,839 --> 00:39:05,910 This is just a wrap up slide to show you 643 00:39:05,976 --> 00:39:09,213 how accelerating clinical trials in the E.U., 644 00:39:09,280 --> 00:39:10,548 the Clinical Trial Regulation, 645 00:39:10,614 --> 00:39:12,783 and the Clinical Trials Information System 646 00:39:13,551 --> 00:39:17,888 is impacting the clinical research environment in Europe, 647 00:39:17,955 --> 00:39:20,891 and which benefits it's bringing for patients. 648 00:39:23,027 --> 00:39:24,695 This is just a summary. 649 00:39:24,762 --> 00:39:27,098 I will not go through it because in fact, 650 00:39:27,164 --> 00:39:32,636 this is just wrapping up what I have shown in this presentation. 651 00:39:38,809 --> 00:39:42,279 And before I finalize, just a few questions 652 00:39:43,180 --> 00:39:46,417 to see where is your knowledge 653 00:39:46,484 --> 00:39:48,786 in terms of the clinical trials in Europe. 654 00:39:50,988 --> 00:39:54,225 In the E.U., the European Medicines Agency is responsible 655 00:39:54,291 --> 00:39:56,761 for the authorization of clinical trials? 656 00:39:56,827 --> 00:40:04,034 True or false? This is in fact false. 657 00:40:05,469 --> 00:40:09,106 The authorization of clinical trials in the European Union 658 00:40:09,173 --> 00:40:12,376 is under the responsibility of the Member States. 659 00:40:14,612 --> 00:40:17,615 In each E.U. Member State, both the regulatory authority 660 00:40:17,681 --> 00:40:20,518 and the ethics committee need to issue decisions 661 00:40:20,584 --> 00:40:25,656 on the authorization of a trial? This is false as well. 662 00:40:27,057 --> 00:40:29,894 One of the advantages of the Clinical Trial Regulation 663 00:40:29,960 --> 00:40:33,030 is that it brought this single decision 664 00:40:33,097 --> 00:40:35,099 by each Member State concerned. 665 00:40:35,733 --> 00:40:37,501 So, the decision of a Member State 666 00:40:37,568 --> 00:40:40,337 is the common decision from the ethics committee 667 00:40:40,404 --> 00:40:42,606 and the national competent authority. 668 00:40:44,842 --> 00:40:47,812 A tacit approval of a clinical trial in a Member State 669 00:40:47,878 --> 00:40:51,982 concerned is possible if the Member State doesn't issue 670 00:40:52,049 --> 00:40:54,885 a decision within the established timelines? 671 00:40:56,954 --> 00:40:59,423 This is true. And this is, again, 672 00:40:59,490 --> 00:41:02,660 an advantage brought by the Clinical Trial Regulation. 673 00:41:03,227 --> 00:41:04,895 So, there are strict timelines 674 00:41:04,962 --> 00:41:08,032 which brings pre-visibility to the sponsors. 675 00:41:08,098 --> 00:41:12,536 And if a Member State concerned does not issue a decision, 676 00:41:12,603 --> 00:41:15,806 then the decision in that Member State 677 00:41:15,873 --> 00:41:18,542 will be the one of the reporting Member State 678 00:41:18,609 --> 00:41:21,245 for the assessment of Part I of the dossier. 679 00:41:22,947 --> 00:41:24,615 The sponsors of a clinical trial 680 00:41:24,682 --> 00:41:27,551 need to draft a summary of results for laypersons 681 00:41:27,618 --> 00:41:29,820 which will become publicly available? 682 00:41:31,722 --> 00:41:37,661 This is true. And again, it's one of the tools 683 00:41:37,728 --> 00:41:39,797 brought by the Clinical Trial Regulation 684 00:41:40,331 --> 00:41:42,867 with the aim of increased transparency. 685 00:41:44,201 --> 00:41:48,405 12 months after the end of the clinical trial in the E.U., 686 00:41:48,939 --> 00:41:53,077 this sponsor needs to submit this laypersons summary. 687 00:42:09,260 --> 00:42:11,595 And this is it for this lecture. 688 00:42:12,096 --> 00:42:17,234 I hope you have learned a bit about E.U. regulatory framework 689 00:42:17,301 --> 00:42:20,404 for the authorization and supervision of clinical trials. 690 00:42:21,672 --> 00:42:23,340 Many thanks for your attention.