The MDCG have published a guidance document on preparing the clinical investigation plan, in accordance with Section 3 of Chapter II of Annex XV of the MDR as well as the international standard ISO 14155:2020. The former is the legally required content of the Clinical Investigation Plan while the latter addresses good clinical practice for the design, conduct, recording and reporting of clinical investigations. MDCG 2024-3 is meant to support sponsors developing their CIP by describing in greater detail what type of information is expected in the plan. The guidance also includes a clinical investigation plan synopsis template in Annex I.
The guidance document goes into detail on the following sections:
- General – General introduction on the CIP including CIP reference number; summary of the revision history as applicable; overall synopsis of the clinical investigation; contact details of key stakeholders such as sponsor, legal representative and principal investigator; a brief description of how the clinical investigation is finance and the agreement between the sponsor and site.
- Identification and description of the investigational device including its intended purpose in the clinical investigation, details concerning the manufacturer, description of the specific medical or surgical procedures involved in the use of the investigational device and a background literature review, among others.
- Benefits and risks of the investigational device, clinical procedures and clinical investigation – Type of benefits, both direct and indirect, magnitude, duration of benefit and the medical necessity. As well, an identification of risks should be provided including risk characterization such as types of risks, their likelihood, duration and severity of harm. This section should also summarize the rationale for the benefit-risk ratio of the clinical investigation.
- Relevance of the clinical investigation – Justification of the clinical investigation in the context of the state of the art of clinical practice, including justification for the design and where the clinical investigation fits into the clinical development of the device.
- Objectives and hypotheses – The purpose of the clinical investigation, claims for clinical performance, effectiveness or safety of the investigational device that are to be verified should be described.
- Design of the clinical investigation – The design should be sufficiently detailed with evidence of its scientific robustness and validity. It should include general information such as type of investigation with rationale for choosing it, for its endpoints and for its variables as set out in the clinical evaluation plan; Information on the investigational device and any comparator to be used in the clinical investigation; Details of measures to be taken to minimise bias, such as randomisation, and management of potential confounding factors; Description of the clinical procedures and diagnostic methods relating to the clinical investigation and in particular highlighting any deviation from normal clinical practice; Monitoring plan
- Statistical design and analysis – The CIP shall describe and justify the statistical design and analysis of the clinical investigation and should cover, among others, the analysis population and procedures that take into account all the data; Descriptive statistics of baseline data, treatments, safety data and where applicable, primary and secondary endpoints; Analytical procedures including measures of precision such as confidence intervals.
- Data management – A description should be provided of the procedures implemented which can guarantee that the data generated in the clinical investigation is reliable and robust.
- Modifications of the CIP – The clinical investigation plan shall make it clear that the competent authority shall be notified of all proposed changes to the approved clinical investigation that are likely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation, as required in Article 75 of the MDR.
- Deviations from the CIP – There should be a statement specifying that the investigator is not allowed to deviate from the CIP, except if to protect the rights, safety and well-being of human subjects under emergency circumstances, when the investigator may deviate without prior approval of the sponsor.
- Device accountability – The CIP should include adequate procedures for the accountability and traceability of the investigational, in particular control of access to and adequate storage of the device, follow-up in relation to the device used in the clinical investigation and the return of unused, expired or malfunctioning devices.
- Statements of compliance – The CIP should include statements specifying that the clinical investigation shall be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki; Statement specifying compliance with any relevant international standards and/or consensus guidance, such as the latest version of the international standard ISO 14155; Statement specifying compliance with the national legislation and MDR; Statement specifying that the clinical investigation shall not begin until the required regulatory and ethical assessments have been completed with non-negative outcomes; Statement specifying that any additional requirements imposed by the Ethics Committee or regulatory authority shall be followed; Statement specifying the type of insurance that shall be provided for subjects, if appropriate.
- Informed consent process – The CIP should include a description of the general process for obtaining informed consent, including the process for providing subjects with new information and process for compensation to subjects for participation in the clinical investigation, as needed. If applicable, the description of the process in circumstances where the subject is unable to give informed consent must also be included.
- Adverse events, adverse device effects and device deficiencies – The CIP should include a list of definitions of various adverse events terms, a list of foreseeable adverse events and anticipated adverse device effects, as well as details of the process for recording, follow-up and reporting adverse events and device deficiencies should be described.
- End, suspension or premature termination of the clinical investigation – The CIP should define the end of the clinical investigation, which is important in relation to reporting requirements at the end of the study as outlined in article 77 of the MDR. The clinical investigation plan should also consider appropriate stopping criteria on both subject and study level.
- Arrangements for subjects following participation – The CIP should describe the arrangements for taking care of the subjects after their participation in the clinical investigation has ended, where such additional care is necessary because of the subjects’ participation in the clinical investigation and where it differs from that normally expected for the medical condition in question.
- Publication policy – The CIP should state that the clinical investigation will be registered in a publicly available database, it should indicate that the results of the clinical investigation will be made publicly available and the conditions and timeframes under which the results of the clinical investigation will be offered for publication including the role of the sponsor and criteria for authorship.
- Technical and functional features of the device – The CIP should list the technical and functional features of the device and specify those features which are studied in the clinical investigation. A tabular presentation of the relevant product characteristics of the investigational device is expected with an indication of the associated product specifications and assignment of the expected clinical outcome.
- Bibliography – The CIP should include a list of bibliographic references relating to the clinical investigation.
The guidance document can be accessed using the following link
