The four new consultations, released Thursday from the European Commission, deal with ethical considerations for pharmaceutical trials with minors, risk proportionate approaches in trials, summaries of trial results for non-specialists or “laypersons” and definitions of investigational medical products (IMPs) and use of auxiliary medicinal products (AMPs).
The consultations offer respondents a chance to weigh in (comments on the four consultations are due by 31 August) on updates to EC documents, particularly with regard to offering more information on how a risk proportionate approach to trials can be implemented and how documents can be aligned with current research.
Trials With Children
As part of the revision of the 49-page document, "Ethical Considerations for Clinical Trials on Medicinal products conducted with Minors," and in preparation for the implementation for the Clinical Trials Regulation (EU) No 536/2014, the EC says it’s looking to align the document with the regulation “and with the latest (scientific) insights on research with children.”
The major changes were made on the following:
- More emphasis on the evolving maturity of children, underlying the requirement of the new trial regulation to respect the explicit wish of a minor to refuse participation in, or to withdraw from, a clinical trial at any time;
- Recommendations on the requirement of participation of the minor in the informed consent process;
- Introduction of the term “agreement,” equivalent to the term “assent” in medical literature, since the regulation reserves the term “assent” to have legal value in some EU member states;
- More emphasis on informed consent as a continual process;
- More emphasis on burden, next to risk, its subjective nature and the importance to involve children in the assessment and minimization 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;
- Additional recommendations for emergency situations;
- New insights on trial designs and sampling methods;
- Additional recommendations on trials with female adolescents;
- Updates on data protection; and
- Updates on GCP compliance.
The EC is seeking comment on trials on minors in emergency situations and other relevant references to improve the document, among other topics.
In terms of the document known as, "Risk proportionate approaches in clinical trials," which was developed in preparation for the implementation of the new trial regulation, the EC is looking for “further information on how a risk proportionate approach can be implemented in clinical trials” and how to support and facilitate such adaptations.
This document is based on the requirements of the regulation and offers more information on how such a risk proportionate approach can be implemented, as well as the locations in the regulation that support and facilitate such adaptations.
“This guideline applies to all sponsors, commercial as well as academic and all types of clinical trials, from early development of unauthorised products to clinical research conducted in the post-authorisation phase,” the commission says. “Thus it is addressed both to those clinical trials that are intended to be included in the application for a marketing authorisation for the medicinal product under investigation, clinical trials with novel IMPs and to trials using only IMPs with a marketing authorisation, within or outside the terms of their marketing authorisation.”
The regulation provides for less stringent rules for monitoring trials and the content of the trial master file for certain trials which pose only “a minimal additional risk to subject safety (as defined in Article 2(3) of the Regulation) compared to normal clinical practice.”
Annex V of the EU Clinical Trials Regulation contains 10 elements that should be included in the summary of the results of the clinical trial for laypersons.
This latest document offers more details on the information that should be provided for each of these elements.
General considerations include:
- Develop the summary for a general public audience and do not assume any prior knowledge of the trial;
- Develop the layout and content for each section in terms of style, language and literacy level to meet the needs of the general public;
- Keep the document as short as possible;
- Focus on unambiguous, factual information;
- Ensure no promotional content is included; and
- Consider involving patients, patient representatives, or advocates in the development and review of the summary information to ensure that it truly meets their needs.
IMPs and AMPs
This document seeks to clarify and provide additional guidance on the definition of IMPs and recommendations about the use of auxiliary medicinal products (AMPs) in accordance with EU legislation.
Ethical considerations for clinical trials on medicinal products conducted with minors
Risk proportionate approaches in clinical trials
Summary of Clinical Trial Results for Laypersons
Definition of Investigational Medicinal Products (IMPs) and use of Auxiliary Medicinal Products (AMPs)