At the beginning of June, the EU Commission launched four public consultations regarding the conduct of clinical trials. Submissions to the various public consultations must be made by 31 August 2016. These consultations are designed to gather public opinion regarding different aspects of clinical trial procedure in anticipation of the implementation of Regulation 536/2014 (“Regulations”). Following the recent referendum result the advances brought about by the Regulations, and other EU regulations, has been thrown into doubt.
The Regulations are expected to take practical effect from October 2018. This takes into consideration, the time that it will take to ensure that the supporting technological infrastructure is approved and becomes operational.
1. Ethical considerations of clinical trials with children
This consultation is designed to ensure that minors i.e. individuals from birth up to the age of legal consent are protected during the conduct of clinical trials. The purpose of the consultation is to develop recommendations that will encompass the new legislative framework embodied by the Regulations and current paediatric knowledge regarding the conduct of clinical trials and their design.
The scope of these recommendations will be far reaching and will apply to all persons involved in any stage of a clinical trial. This includes sponsors of clinical trials, assessors, regulatory authorities, pharmaceutical companies, insurance companies (regarding trial subjects), investigators (including all trial-related staff) of clinical trials performed in children of all ages, families, and participants.
The consultation recognises the specific vulnerabilities of minors during the clinical trials process and focuses on the following areas:
- Strengthening the concept of informed consent - involvement of minors in the informed consent process and emphasising its status as a continual process;
- More emphasis on the evolving maturity of children which involves respect for a minor’s decision to refuse participation in, or to withdraw from a clinical trial at any time;
- Introduction of the term ‘agreement’ as the equivalent to the term ‘assent’;
- Additional recommendations for emergency situations;
- Additional recommendations on trials with female adolescents;
- Addition of the latest insights on trial designs and sampling methods;
- Updates on Good Clinical Practice compliance;
- Updates on data protection;
- More emphasis on burden, next to risk, its subjective nature and the importance to involve children in the assessment and minimisation of burden;
- Assessment of the relationship between benefit, risk and burden, in particular when there is no direct benefit for the participant, only benefit for the population, and the risk and burden should be minimal in comparison to the standard treatment;
2.Strategies to guarantee a risk proportionate approach to clinical trials
The Regulations recognise that some clinical trials pose only a minimal additional risk to patient safety in contrast with the normal clinical practice. They also encourage the development of a risk proportionate approach to the design and conduct of clinical trials.
This consultation is designed to facilitate this development. A risk proportionate approach involves consideration of the type of product that is being investigated and the corresponding risk to subject safety. Adopting this approach will limit the risk to clinical trial patients that arises from the trial procedure.
Additionally, it replaces the “one size fits all” approach to the development of trial procedure prevalent under the Good Clinical Practice (GCP) regime with a nuanced trial specific approach. This development is to be welcomed from a volunteer/patient safety perspective.
3. Summaries for lay persons
The Regulations require that the summary results of clinical trials are publicly available on the EU database and portal.
This consultation will consider the style, language and format of the lay summaries so that recommendations and templates for the summaries will be developed that will be used by clinical trial sponsors and investigators. The recommendations will only cover the lay person summaries included in the EU database. Due to the wide audience that these summaries are intended to attract, the primary consideration is to create a concise, clear and accessible summary document that meets the needs of the general public.
This development is to be welcomed as the volunteer/ patient will have better understanding of the impact of their involvement in a clinical trial. In our experience this has been a common complaint of those participating in clinical trials.
4.Definition of investigational medicinal products and the use of the auxiliary medicinal products
This consultation is designed to flesh out the meaning of two important terms in the Regulations. Firstly, it intends to clarify the Regulation definition of investigational medicinal product by developing a common EU wide definition of the term. Secondly, it will provide recommendations on the use of auxiliary medicinal products.
The announcement of these consultations suggests that the EU is determined to ensure that the Regulations have a meaningful impact on the conduct and design of clinical trials in Europe. Should we find ourselves no longer part of the EU, it is important that these Regulations continue to be followed to ensure that volunteer/ patient safety and informed consent is at the heart of pharmaceutical development.