The implementation of the Medical Device Regulation (EU) 2017/745 (hereinafter referred to as MDR) has set new requirements for performing clinical investigations. Indeed, whereas the previous directives (93/42/CEE&90/385/EEC) only dedicated an article to this matter, the MDR has 20 articles and an annex.
All these changes may seem challenging to implement, especially in the case of ongoing clinical investigations. To support sponsors with the design and implementation of clinical investigation, we have developed a practical guide bringing together the experience of our clinical team.
Where does the complexity of clinical research come from?
To answer this question, we may first define a clinical investigation. According to the international standard ISO 14155 on Good Clinical Practice (Clinical investigation of medical devices for humans, with the last version released being ISO 14155:2020), a clinical investigation is a systematic investigation in one or more human subjects to evaluate the clinical performance, effectiveness or safety of a medical device.
ISO 14155 provides guidance and requirements for the design, conduct, recording and reporting of clinical investigations in accordance with the MDR and the ethical principles set out in the Declaration of Helsinki. Together, these documents set out the basis for ensuring the safety of clinical investigations of medical devices. These documents must be followed by sponsors, investigators and other stakeholders (clinical research organisations, ethics committees, regulatory authorities) to ensure:
- That rights, safety, dignity and well-being of the participants are protected and prevail over interests of science and society; and,
- That the clinical data generated are clinically valid, reliable and robust.
Therefore, it is essential to ensure that clinical investigations accomplish all legal and contractual aspects, contain all the required documentation and meet all ethical requirements. This process is analogous to a mechanical watch: all springs within the clinical clockwork must run correctly. However, the lack of knowledge in the field, the pressure to avoid delays, or even the lack of resources, among other issues, can lead clinical investigations to failure.
Tips for conducting successful clinical investigations
Here we present some tips based on our clinical investigation experience with medical devices:
1. Always protect the rights, safety and well-being of human subjects
- Ensure the participants/legal representatives are informed and provide adequate informed consent.
- Ensure participant’s data protection.
- Provide insurance or a damaged compensation system.
- In the case of sudden finalisation of a clinical investigation, do guarantee a continuous standard of care to participants.
- Don’t influence (financially or other) the subject/legal representative to participate in a clinical investigation.
- Don’t remove or share any source document regarding participant’s data outside the clinical site
- If in doubt of the conditions/malfunction of a drug/device under investigation, don’t administer/provide them to participants.
2. Ethical considerations
- Ensure all inclusion/exclusion criteria do not ease participating or excluding vulnerable populations or subjects from the trials.
- Don’t provide non-approved information to the participants. The informed consent and any other written communication provided to the participants must have been previously approved by the Ethics Committee.
3. Data management and Biostatistical considerations
- Ensure transparency. If any change/correction is required in the CRF, site visit log or any other document, identify all of the changes, date and sign them, including a rationale for those changes.
- Ensure all statistical considerations, with justification, and include power calculations (if applicable).
- Ensure and record (training log) that all parts of the clinical investigation have been adequately trained in the particular project.
- Inform of all participant’s adverse events/serious adverse events to the monitor/CRO/person responsible in the adequate, timely manner established.
- Ensure the collaboration between all parties involved in the clinical investigation (Sponsor-CRO-Principal Investigator).
How can AKRN help?
AKRN’s clinical team has extensive experience in the design, conduct, recording and reporting of clinical investigations and a thorough understanding of the regulatory requirements for conducting clinical investigations with medical devices.
Our team are specialists in:
- Design and conduct of pre- and post-market clinical investigations across Europe
- Package preparation and regulatory submissions to Ethics committee and competent authorities
- Design and management of Case Report Forms and Electronic Data Capture platforms
- Project management
- Selection and qualification of sites, and contact with key opinion leaders
- Clinical Investigation monitoring
- Data management
- Data analysis and clinical report writing
Contact us to learn how to support you in your clinical investigation with medical devices.
About the authors
Laura Martínez, Ph.D. Regulatory Affairs Scientist
Albert Negrete, Ph.D. Regulatory Affairs Scientist
Ariadna Navarro, Ph.D. Associate Director RA & QA