53 Amendments of Roberta ANGELILLI related to 2012/0192(COD)
Amendment 82 #
Proposal for a regulation
Recital 2
Recital 2
(2) In order to allow for independent control as to whether these principles are adhered to, a clinical trial should be subject to prior authorisation. This authorisation should include scientific, ethical and administrative aspects.
Amendment 87 #
Proposal for a regulation
Recital 5
Recital 5
(5) Experience with Directive 2001/20/EC has also shown that the aim of simplifying and harmonising the administrative provisions governing clinical trials in the Union cannot be achieved in the legal form of a Directive but can only be achieved with the legal form of a Regulation. Only the legal form of a Regulation ensures that the Member States base their assessment of an application for authorisation of a clinical trial on identical criteria, rather than on diverging national transposition measures. This holds not only for the entire authorisation process, but also for all other issues addressed in this Regulation, such as safety reporting during clinical trials, and the requirements for labelling of the medicinal products used in the context of a clinical trial.
Amendment 89 #
Proposal for a regulation
Recital 6
Recital 6
(6) The Member States concerned should cooperate in assessing a request for authorisation of a clinical trial. This cooperation should not include aspects of an intrinsically national nature, nor ethical aspects of a clinical trial, such as informed consent.
Amendment 98 #
Proposal for a regulation
Recital 9
Recital 9
(9) The risk to subject safety in a clinical trial mainly stems from two sources: the investigational medicinal product and the intervention. Many clinical trials, however, pose only a minimal additional risk to subject safety compared to normal clinical practice. This is in particular the case where the investigational medicinal product is covered by a marketing authorisation (i.e. the quality, safety and efficacy has already been assessed in the course of the marketing authorisation procedure) and where the intervention poses only very limited additional risk to the subject compared to normal clinical practice. Those ‘low-intervention clinical trials’ are often of crucial importance to assess standard treatments and diagnoses, thereby optimising the use of medicinal products and thus contributing to a high level of public health. They should be subject to less stringent administrative rules, such as shorter deadlines for approval.
Amendment 117 #
Proposal for a regulation
Recital 13
Recital 13
(13) The authorisation of a clinical trial should address all aspects in relation to subject protection and data reliability and robustness. The permission to conduct a clinical trial should therefore be contained in one single administrative decision by the Member State concerned.
Amendment 118 #
Proposal for a regulation
Recital 14
Recital 14
(14) It should be left to the Member State concerned to determine the appropriate body or bodies to be involved in this assessment. These bodies should be established according to the ICH Topic E 6 (R1) Guideline for Good Clinical Practice, which details the responsibilities, composition, functions, operations and procedures. This decision is a matter of internal organisation of each Member State. Member States, when determining the appropriate body or bodies, should ensure the involvement of lay persons and patients. They should also ensure that the necessary expertise is available. In any case, however, and in accordance with international guidelines, the assessment should be done jointly by a reasonable number of persons who collectively have the necessary qualifications and experience. The persons assessing the application should be independent from the sponsor, the institution of the trial site, and the investigators involved, as well as free of any other undue influence.
Amendment 122 #
Proposal for a regulation
Recital 22
Recital 22
(22) The human dignity and right to the integrity of the person are recognized in the Charter of Fundamental rights of the European Union. In particular, the Charter requires that any intervention in the field of biology and medicine cannot be performed without free and informed consent of the person concerned. Directive 2001/20/EC contained an extensive set of rules for the protection of subjects. These rules should be upheldSubjects from vulnerable population groups such as incapacitated subjects, minors or other vulnerable people, require additional protection measures. Directive 2001/20/EC contained an extensive set of rules for the protection of subjects including children and incapacitated subjects. In addition, specific rules to be applied to the paediatric population have been stated in the Ethical Recommendation (EC, 2008). These rules should be upheld and further integrated in order to cover all the vulnerable groups (pregnancy females, old people, emergency, etc). Regarding the rules concerning the determination of the legal representative of incapacitated persons and minors, those rules diverge in Member States. It should therefore be left to Member States to determine the legal representative of incapacitated personsubjects and minors.
Amendment 128 #
Proposal for a regulation
Recital 24
Recital 24
(24) In accordance with international guidelines, the free and informed consent of the subject should be given in writing, save in exceptional situations. It should be based on information which is clear, relevant and understandable to the subject. Where possible, such information should be given orally, with the opportunity for the subject to ask questions, and the subject should be provided with comprehensive written information which he or she is allowed to keep. Adequate time should be provided for the subject to consider his or her decision.
Amendment 130 #
Proposal for a regulation
Recital 24 a (new)
Recital 24 a (new)
(24a) In accordance to the Ethical Recommendations (EC, 2008) and in addition to what is stated before, in paediatric clinical trials appropriate procedures on the informed assent should be applied. These procedures should take into account the age and maturity of children.
Amendment 135 #
Proposal for a regulation
Recital 29
Recital 29
(29) The members of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) have agreed on a detailed set of guidelines for good clinical practice which are now an internationally accepted standard for designing, conducting, recording and reporting clinical trials, consistent with principles that have their origin in the World Medical Association's Declaration of Helsinki. When designing, conducting, recording and reporting clinical trials, detailed questions may arise as to the appropriate quality standard. In such a case, the ICH guidelines on good clinical practice should be used as guidance for the application of the rules set out in this Regulation, provided that there is no other specific guidance issued by the Commission and that those guidelines are without prejudice to this Regulationthe ICH guidelines on good clinical practice (GCP) and other applicable guidelines published by the EC should be used as guidance for the application of the rules set out in this Regulation. To this aim GCP should be made part of this Regulation and included in Annex [xxx].
Amendment 136 #
Proposal for a regulation
Recital 30
Recital 30
Amendment 138 #
Proposal for a regulation
Recital 31
Recital 31
Amendment 140 #
Proposal for a regulation
Recital 32
Recital 32
Amendment 141 #
Proposal for a regulation
Recital 33
Recital 33
Amendment 143 #
Proposal for a regulation
Recital 34
Recital 34
Amendment 144 #
Proposal for a regulation
Recital 35
Recital 35
Amendment 145 #
Proposal for a regulation
Recital 36
Recital 36
Amendment 147 #
Proposal for a regulation
Recital 37
Recital 37
Amendment 151 #
Proposal for a regulation
Recital 38
Recital 38
Amendment 152 #
Proposal for a regulation
Recital 39
Recital 39
Amendment 153 #
Proposal for a regulation
Recital 40
Recital 40
Amendment 154 #
Proposal for a regulation
Recital 41
Recital 41
Amendment 156 #
Proposal for a regulation
Recital 44
Recital 44
(44) The sponsor of a clinical trial may be located in a third country. In order to facilitate supervision and control, a sponsor located in a third country should establish a contact personlegal representative in the Union to allow for the competent authority of the Member State concerned to communicate with the sponsor. That contact person may be a legal or a natural person.
Amendment 161 #
Proposal for a regulation
Recital 47
Recital 47
(47) At present, such damage compensation is provided by way of insurance. This insurance may cover damages to be paid to the subject by the sponsor and investigator in the case of established liability. It may also compensate the subject directly without prior establishment of the liability of the sponsor or investigator. Compensation may also cover medical care for long or medium term physical injuries, pain and suffering. Experience shows that the insurance market is small and costs for insurance coverage are disproportionately high. Moreover, as liability regimes differ widely between Member States, it is difficult and burdensome for the sponsor of a multinational trial to obtain insurance in accordance with those national laws. Therefore, each Member State should establish a national indemnification mechanism which compensates subjects in accordance with the laws of that Member State, and provide patients with clear and accessible information to facilitate the access to the compensation systems.
Amendment 177 #
Proposal for a regulation
Recital 63
Recital 63
(63) This Regulation is in accordance with the Convention on Human Rights and Biomedecine (1997) and its Additional Protocol on biomedical research (2005) of the Council of Europe and the International Convention on the rights of the Child (UN-1989). It is line with the major international guidance documents on clinical trials, such as the most recent (2008) version of the World Medical Association's Declaration of Helsinki and ICH-GCP good clinical practice, which has its origins in the Declaration of Helsinki. The WHO-CIOMS guidelines are also taken into account.
Amendment 231 #
Proposal for a regulation
Article 2 – paragraph 2 – point 16
Article 2 – paragraph 2 – point 16
(16) ‘'Minor’': a subject who is, according to the laws of the Member State concerned, under the age of legal competence to give informed consentmakes part of the paediatric population, as defined in Regulation(EC) No 1901/2006 on medicinal products for paediatric use;
Amendment 236 #
Proposal for a regulation
Article 2 – paragraph 2 – point 19 a (new)
Article 2 – paragraph 2 – point 19 a (new)
(19 a) 'Informed assent': a process by which, whenever appropriate, a minor agrees to participate in a particular trial, after having received, together with his parents, adequate and adapted information, and by which a minor is involved in discussions and the decision- making process in order to respect their evolving capacities.
Amendment 240 #
Proposal for a regulation
Article 2 – paragraph 2 – point 30 a (new)
Article 2 – paragraph 2 – point 30 a (new)
(30a) 'Adverse reaction': a response to a medicinal product which is noxious and unintended;
Amendment 242 #
Proposal for a regulation
Article 2 – paragraph 2 – point 30 c
Article 2 – paragraph 2 – point 30 c
(30 c) 'Ethics committee': An independent body in a Member State, consisting of healthcare professionals and non-medical members, whose responsibility it is to protect the rights, safety and well-being of subjects involved in a trial and to provide public assurance of that protection, by, amongst others, expressing an opinion on the trial protocol, on the suitability of the investigators and the adequacy of facilities, and on the methods and documents to be used to inform trial subjects and obtain their informed consent;
Amendment 248 #
Proposal for a regulation
Article 3 – paragraph 1 – indent 2 a (new)
Article 3 – paragraph 1 – indent 2 a (new)
- an opinion of an Institutional Review Board (IRB) / Independent Ethics Committee (IEC) has been issued.
Amendment 258 #
Proposal for a regulation
Article 5 – paragraph 1 – subparagraph 1 a (new)
Article 5 – paragraph 1 – subparagraph 1 a (new)
Before submitting the application, the sponsor shall obtain a unique EudraCT number from the EudraCT Community Clinical Trial System by the procedure described in the current version of the Detailed guidance on the European clinical trials database (EudraLex, Volume 10).
Amendment 302 #
Proposal for a regulation
Article 6 – paragraph 1 – point d a (new)
Article 6 – paragraph 1 – point d a (new)
(da) The adequateness of the consent and assent process proposal according to Chapter V;
Amendment 303 #
Proposal for a regulation
Article 6 – paragraph 1 – point d b (new)
Article 6 – paragraph 1 – point d b (new)
(db) Compliance with the requirements for informed consent as set out in Chapter V;
Amendment 304 #
Proposal for a regulation
Article 6 – paragraph 1 – point d c (new)
Article 6 – paragraph 1 – point d c (new)
(dc) Compliance with Directive 95/46/EC;
Amendment 330 #
Proposal for a regulation
Article 7 – paragraph 1 – subparagraph 1 – introductory part
Article 7 – paragraph 1 – subparagraph 1 – introductory part
1. EWithout prejudice to the aspects covered by Part I as referred to in Article 6, each Member State concerned shall assess, for its own territory, the application with respect to the following aspects:
Amendment 332 #
Proposal for a regulation
Article 7 – paragraph 1 – subparagraph 1 – point a
Article 7 – paragraph 1 – subparagraph 1 – point a
Amendment 336 #
Proposal for a regulation
Article 7 – paragraph 1 – subparagraph 1 – point d
Article 7 – paragraph 1 – subparagraph 1 – point d
Amendment 372 #
Proposal for a regulation
Article 9 – paragraph 1
Article 9 – paragraph 1
1. An institutional review board (IRB) / independent ethics committee (IEC) is in charge of the assessment described in this chapter. According to the rules governing the composition and responsibilities of the IRB/IECs, Member States shall ensure that the persons validating and assessing the application do not have conflicts of interest, are independent of the sponsor, the institution of the trial site and the investigators involved, as well as free of any other undue influence.
Amendment 381 #
Proposal for a regulation
Article 10 – paragraph 1
Article 10 – paragraph 1
1. Where the subjects are minors, specific consideration shall be given to the assessment of the application for authorisation of a clinical trial on the basis of paediatric expertise or after taking advice on clinical, ethical and psychosocial problems in the field of paediatrics, according to the ICH Topic E11 guideline and the EU Ethical Recommendations (EC, 2008).
Amendment 437 #
Proposal for a regulation
Article 25 – paragraph 1 – subparagraph 1 – point a
Article 25 – paragraph 1 – subparagraph 1 – point a
(a) the conduct of the trial, including the scientific context and arrangements taken, methodological and ethical context,
Amendment 438 #
Proposal for a regulation
Article 25 – paragraph 1 – subparagraph 1 – point d a (new)
Article 25 – paragraph 1 – subparagraph 1 – point d a (new)
(da) the informed consent/assent process.
Amendment 462 #
Proposal for a regulation
Article 29 – paragraph 1
Article 29 – paragraph 1
1. Informed consent shall be written, dated and signed and given freely byWritten information given to the subject or his or and/or ther legal representative after having been duly informed of the nature, significance, implications and risks of the clinical trial. It shall be appropriately documented. Where the subject is unable to write, oral consent in the presence of at least one impartial witness may be given in exceptional cases. The subject or his or her legal representative shall be provided with a copy of the document by which informed consent has been givenfor the purposes of obtaining his or her informed consent shall be kept concise, clear, relevant, and understandable to a lay person. It shall include both medical and legal information. It shall inform the subject about his or her right to revoke his or her informed consent. It shall provide a clear and exhaustive information related to legal remedies and conditions to access to a system of indemnisation, in case of injuries incurred during the trial.
Amendment 485 #
Proposal for a regulation
Article 31 – paragraph 1 – point a
Article 31 – paragraph 1 – point a
(a) the written informed consent of the legal representative has been obtained, whereby consent shall represent the minor's presumed will;
Amendment 489 #
Proposal for a regulation
Article 31 – paragraph 1 – point c
Article 31 – paragraph 1 – point c
(c) the explicit wish of aassent of the minor who is capable of forming an opinion and assessing this information to refuse participation in, or to be withdrawn from, the clinical trial at any time, is duly taken into consideration by the investigator in accordance with his or her age and maturity, has been obtained;
Amendment 495 #
Proposal for a regulation
Article 31 – paragraph 1 – point h a (new)
Article 31 – paragraph 1 – point h a (new)
(ha) the indemnification/insurance system include specific provisions related to long- term effects on the development of the child;
Amendment 497 #
Proposal for a regulation
Article 31 – paragraph 1 – point h c (new)
Article 31 – paragraph 1 – point h c (new)
(h c) the trial does not replicate other trials based on the same hyphothesis and age-appropriate formulations are used;
Amendment 499 #
Proposal for a regulation
Article 31 – paragraph 1 – point h e (new)
Article 31 – paragraph 1 – point h e (new)
(he) a restrictive use of placebo is adopted and, if relevant, a Specific Data Safety Monitoring Board (DSMB) is set up;
Amendment 557 #
Proposal for a regulation
Article 38 – paragraph 2
Article 38 – paragraph 2
2. The time period for reporting shall take account of the severityriousness of the reaction. Where necessary to ensure timely reporting, the sponsor may submit an initial incomplete report followed up by a complete report.
Amendment 560 #
Proposal for a regulation
Article 38 – paragraph 3
Article 38 – paragraph 3
3. Where a sponsor, due to a lack of resources because of the non-profit nature of the trial, does not have the possibility to report to the electronic database referred to in Article 36, it may report to the Member State where the suspected unexpected serious adverse reaction occurred. That Member State shall report the suspected unexpected serious adverse reaction in accordance with paragraph 1.
Amendment 576 #
Proposal for a regulation
Article 44 – paragraph 2
Article 44 – paragraph 2
Without prejudice to Union legislation and specific guidelines of the Commission the sponsor and the investigator, when drawing up the protocol and when applyingconducting a clinical trial according to this Regulation and the protocol, shall take due account of the quality standards set by the detailedrefer to the international guidelines on good clinical practice of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), as reported in Annex [xxx].
Amendment 577 #
Proposal for a regulation
Article 44 – paragraph 3
Article 44 – paragraph 3
The Commission shall make the detailed international guidelines on good clinical practice referred to in the second paragraph publicly available in Annex [xxx] of this Regulation, and shall regularly update them.
Amendment 580 #
Proposal for a regulation
Article 45 – paragraph 1 – introductory part
Article 45 – paragraph 1 – introductory part
The sponsor shall adequately monitor the conduct of a clinical trial. The extent and nature of the monitoring shall be determined by the sponsor on the basis of all characteristics of the clinical trial, includingconduct in accordance with the current GCP guideline and should take into account the following characteristics:
Amendment 591 #
Proposal for a regulation
Article 50 – paragraph 1
Article 50 – paragraph 1
1. The sponsor shall notify the Member States concerned through the EU portal and without undue delay, of all unexpected events which affect the benefit-risk balance of the clinical trial, but are not suspected unexpected serious adverse reactions as referred to in Article 38.