Good clinical practice in clinical investigations for medical devices

Revision of ISO 14155:2011 circulated for ballot

The revision of the Medical Devices Regulation (MDR) places increased emphasis on having sufficient clinical evidence to support the safety and performance of medical devices. Clinical evidence comes from the critical evaluation of clinical data. Clinical data includes:

• relevant scientific literature;
• results of all available clinical investigations;
• information on currently available alternative treatment options.

Article 62 of the MDR provides general requirements for clinical investigations conducted to demonstrate conformity of devices. This includes requirements that clinical investigations are conducted in a manner that protects the rights, safety, dignity and wellbeing of the subjects. It also requires that the clinical data generated are scientifically valid, reliable and robust. This is a requirement to comply with good clinical practice (GCP).

The proposed text of the third edition of ISO 14155 - Clinical investigation of medical devices for human subjects — Good clinical practice - has been circulated for ballot as a draft International Standard (DIS). The DIS stage is the final opportunity to submit technical comments. The revision addresses good clinical practice for the design, conduct, recording and reporting of pre-market clinical investigations carried out in human subjects to assess the clinical performance or effectiveness and safety of medical devices. The principles also apply to post-market clinical investigations. The document specifies general requirements to:

• protect the rights, safety and well-being of human subjects,
• ensure the scientific conduct of the clinical investigation and the credibility of the clinical investigation results,
• define the responsibilities of the sponsor and principal investigator, and
• assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of medical devices.

The main changes compared to the previous edition are a reinforcement of risk management throughout the process of a clinical investigation and inclusion of:

• a summary section of GCP principles;
• reference to registration of the clinical investigation in a publicly accessible data base;
• guidance with regards to clinical quality management;
• risk-based monitoring;
• guidance on statistical considerations;
• guidance for ethics committees;
• clarification of applicability in different stages of clinical development;
• guidance on clinical investigation audits.

The revised standard recognised the close relationship between the risk management process and the conduct of clinical investigations. The risk management process:

• identifies hazards associated with investigational devices,
• estimates and evaluates associated risks,
• identifies risk controls to reduce these risks to an acceptable level, and
• monitors the effectiveness of risk controls during clinical investigations.

The revised edition of ISO 14155 has a normative reference to ISO 14971 - Medical devices — Application of risk management to medical devices. Compliance with ISO 14971 is specified in regards to:

• estimating the risks associated with the investigational device prior to design and conduct of a clinical investigation; and,
• conducting a comprehensive risk assessment if an unanticipated serious event identifies the possibility of an unacceptable risk.

This is an opportunity to review and assess the implications of the changes proposed to this key standard. Given the focus in the MDR on the importance of clinical evidence, and the timescales for setting up and conducting clinical investigations, it is important to keep up-to-date with the latest thinking on this important topic.