Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance) (c. 745)

ANNEX XV CLINICAL INVESTIGATIONS

CHAPTER III OTHER OBLIGATIONS OF THE SPONSOR

1. The sponsor shall undertake to keep available for the competent national authorities any documentation necessary to provide evidence for the documentation referred to in Chapter II of this Annex. If the sponsor is not the natural or legal person responsible for the manufacture of the investigational device, that obligation may be fulfilled by that person on behalf of the sponsor.

2. The Sponsor shall have an agreement in place to ensure that any serious adverse events or any other event as referred to in Article 80(2) are reported by the investigator or investigators to the sponsor in a timely manner.

3. The documentation mentioned in this Annex shall be kept for a period of at least 10 years after the clinical investigation with the device in question has ended, or, in the event that the device is subsequently placed on the market, at least 10 years after the last device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.

Each Member State shall require that this documentation is kept at the disposal of the competent authorities for the period referred to in the first subparagraph in case the sponsor, or its contact person or legal representative as referred to in Article 62(2) established within its territory, goes bankrupt or ceases its activity prior to the end of this period.

4. The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation.

5. The Sponsor shall complete the follow-up of investigation subjects.

6. The Sponsor shall provide evidence that the investigation is being conducted in line with good clinical practice, for instance through internal or external inspection.

7. The Sponsor shall prepare a clinical investigation report which includes at least the following:

• Cover/introductory page or pages indicating the title of the investigation, the investigational device, the single identification number, the CIP number and the details with signatures of the coordinating investigators and the principal investigators from each investigational site.

• Details of the author and date of the report.

• A summary of the investigation covering the title, purpose of the investigation, description of the investigation, investigational design and methods used, the results of the investigation and conclusion of the investigation. The completion date of the investigation, and in particular details of early termination, temporary halts or suspensions of investigations.

• Investigational device description, in particular clearly defined intended purpose.

• A summary of the clinical investigation plan covering objectives, design, ethical aspects, monitoring and quality measures, selection criteria, target patient populations, sample size, treatment schedules, follow-up duration, concomitant treatments, statistical plan, including hypothesis, sample size calculation and analysis methods, as well as a justification.

• Results of the clinical investigation covering, with rationale and justification, subject demographics, analysis of results related to chosen endpoints, details of subgroup analysis, as well as compliance with the CIP, and covering follow-up of missing data and of patients withdrawing from the clinical investigation, or lost to follow-up.

• Summary of serious adverse events, adverse device effects, device deficiencies and any relevant corrective actions.

• Discussion and overall conclusions covering safety and performance results, assessment of risks and clinical benefits, discussion of clinical relevance in accordance with clinical state of the art, any specific precautions for specific patient populations, implications for the investigational device, limitations of the investigation.