Improving the quality and reliability of clinical investigations / MDCG recommendations

The MDCG document number MDCG 2024-3 is a guideline for the preparation of the clinical investigation plan (CIP) for clinical investigations of medical devices.

The guidance provides detailed instructions on what information is expected in the different sections of the CIP in order to prevent questions from competent authorities during the clinical evaluation of clinical investigation applications. It is based on the requirements of Annex XV of the EU Medical Device Regulation (MDR) and the ISO 14155:2020 standard and covers topics such as the description of the investigational medical device, benefit-risk analysis, study objectives, study design, data management and statistical analysis. Although the guidance is not legally binding, it is recognised as best practice and is intended to assist sponsors in developing a structured and comprehensive protocol

The key recommendations are summarised below.

Measures to minimise bias:

1. randomisation and blinding:

• It is recommended to take measures to minimise bias such as randomisation and blinding (masking). These measures should be clearly described in the study protocol.
• Randomisation helps to distribute known and unknown confounders evenly across the study groups.

2. blinding/masking:

• Blinding should be done for patients as well as for clinical staff and evaluators to ensure unbiased assessment of treatment effects.
• The document emphasises the need to define the criteria for access to the blinding code and the circumstances under which blinding may be withdrawn.
• Clear criteria should be established as to who has access to the blinding code and under what circumstances blinding may be cancelled. This is crucial to ensure the integrity of the blinding throughout the study.

3. use of sham procedures:

• If sham procedures are used, they must be thoroughly justified, especially if they are invasive or burdensome. It is important to take ethical considerations into account, as exposing subjects or patients to risks without potential benefits may be questionable.

4. transparency on conflicts of interest:

• Transparency about potential conflicts of interest must be ensured. The document calls for a discussion on how to avoid undue influence on the subjects and the assessment of the endpoints, especially if the inventors of the appliance are closely involved in the conduct of the study and could influence the results in an interest-driven manner.

5. independent review:

• To avoid bias in certain evaluations, an independent committee (e.g., a clinical events committee (CEC)) may be established to determine eligibility, classification of events, and assessment of endpoints.
• A data monitoring committee (DMC) should be established in appropriate situations to continuously monitor the emerging results of the clinical study and make recommendations for continuation or termination of the study.

These recommendations from the MDCG help to improve the quality and reliability of clinical investigations by ensuring that the results are not influenced by systematic bias.

The MDCG is composed of representatives of the European Member States and a representative of the European Commission and draws up recommendations for action that are not legally binding.

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