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Table 2 An overview of the provisions under the EU Clinical Trials Regulation related to the justification of a clinical trial in light of the prior research

From: Redundant trials can be prevented, if the EU clinical trial regulation is applied duly

Provisions under the EU Clinical Trials Regulation

Text of the regulatory provisions (emphasis added)

Aspects that give a leeway for interpretation and the potential to reduce redundancy

Article 6 (1)(b)(i) second indent

An application for a clinical trial shall be assessed with regard to the anticipated therapeutic benefits and taking into account factors such as the relevance of the clinical trial and the current state of scientific knowledge.

•The notions of ‘trial relevance’ and ‘the current state of scientific knowledge’ are broad and can be subject to diverging interpretations.

•‘Relevance’ of a trial might or might not be interpreted as the need to conduct a new trial in view of the existing evidence.

Article 25 (1)(a)

The application dossier for the authorisation of a clinical trial shall contain all required documentation and information necessary for its validation and assessment including the scientific context.

•The notion of ‘scientific context’ is subject to interpretation, especially as far as the scope is concerned.

•Systematic reviews of prior studies and critical analysis of the existing evidence are not explicitly required.

Article 2 (23)

The investigator’s brochure (where applicable) that has to be submitted within the application for the trial authorisation is defined as a compilation of the clinical and non-clinical data on the investigational medicinal product or products which are relevant to the study of the product.

•The requirement concerns data on the experience not only with the investigational medicinal product but also other products which are relevant for the study.

Annex I(E)(25)

Investigator’s brochure has to be prepared in accordance with the state of scientific knowledge and international guidance.

•The criterion ‘in accordance with the state of scientific knowledge’ is of general nature. For instance, a trial can be designed in accordance with the principles and rules of medical statistics – yet, the research question that it intends to address may lack clinical relevance.

Annex I (E)(27)

The information in the investigator’s brochure shall be presented in a concise, simple, objective, balanced and non-promotional form that enables a clinician or investigator to understand it and make an unbiased risk-benefit assessment of the appropriateness of the proposed clinical trial. It shall be prepared from all available information and evidence that supports the rationale for the proposed clinical trial and the safe use of the investigational medicinal product in the clinical trial and be presented in the form of summaries.

•The notion of ‘appropriateness’ in conjunction with the ‘trial rationale’ can be interpreted as the requirement to show that the study intends to resolve a persisting clinical uncertainty that can justify the risks and costs involved.

•The requirement to base the rationale on ‘all available information and evidence’ presupposes extensive search on the part of investigators.

Annex I (G)(46),(47)

The investigational medicinal product dossier shall provide summaries of all available data from previous clinical trials and human experience with the investigational medicinal products.

•The requirement concerns data on the experience only with the investigational medicinal product.

Annex I (D)(17)(c)

The trial protocol shall include a summary of findings from non-clinical studies that potentially have clinical significance and from other clinical trials that are relevant to the clinical trial.

•Notably, the scope of earlier evidence, which has to be taken into consideration, extends to other trials that can be relevant for the proposed study.

•Only references and summaries of findings from previous studies are required to be submitted. Neither systematic reviews, nor critical assessment of earlier studies, nor the explanation of how they informed the design of a proposed trial are explicitly required.

•The notion of ‘relevant’ literature and data that form the scientific background can be interpreted expansively.

Annex I (D)(17)(d)

The trial protocol shall include a summary of the known and potential risks and benefits including an evaluation of the anticipated benefits and risks to allow assessment in accordance with Article 6

Annex I (D)(17)(i)

The trial protocol shall include references to literature and data that are relevant to the clinical trial, and that provide background for the clinical trial.