Mindset XR Module 7: How to document clinical evidence for medical devices

In regulatory terms, conceptualisation is done by writing an Intended Use Statement. This is where you clearly define:

At the end of your intended use statement, it’s also helpful to define any ways in which your device could be foreseeably misused, and what mitigations you have in place to prevent that from happening. 

Finally at the end of the Intended Use, you should define the risk classification of your device, using the specific regulatory rules as described by each jurisdiction you want to deploy your device in. 

This is a high-level document (10-15 pages) which describes all the steps you are going to take to demonstrate scientific, analytical, clinical, and post-market validity. Each activity should be itemised, and milestones should be set to meet before moving onto the next step.  

The clinical evaluation plan is also where you define your clinical benefit. 

Conducting a thorough and systematic literature review can be intensive but is an essential part of the process. A systematic literature review involves following a pre-specified and reproducible search protocol allowing you to find and critically evaluate published scientific evidence relevant to your device. Being systematic in your approach is essential so that your review can be reproduced and updated regularly as new evidence becomes available.

One of the central questions to ask yourself when approaching the literature review is:  

Unlike academic literature reviews, you also need to try and answer the following questions 

During your review you should also look out for best practices in investigation design: 

We recommend you follow the PRISMA guidelines to ensure your literature review is comprehensive and unbiased. 

When documenting the findings of your literature review, it’s helpful to: 

In the discussion section of your literature review, you should cover the following: 

When documenting your literature review process, you should be thorough. In particular, you should: 

You must repeat your literature review at least annually: 

Analytical validity is more related to technical/engineering teams rather than clinical teams, so we won’t focus as much on these documents. Briefly, you need to document:

A clinical investigation is essentially a study protocol which outlines:

At this point, it’s also helpful to remember logistical considerations of clinical investigations: 

ISO 14155 is an international standard which outlines best practice in conducting clinical investigations of medical devices. Within the standard, there are outlines of what needs to be considered in clinical investigation plans, and what needs to be documented in clinical evaluation reports. We suggest you buy the standard, because auditors will check that you have it! 

Researchers conducting investigations on human participants need to have Good Clinical Practice (GCP) certification. This is a free, 4 hour course available on the NIHR website and outlines the fundamental requirements of being safe and ethical during investigations. 

If you are using an experimental device for a medical purpose in a study, you need to notify the MHRA, so they can evaluate the risks of the study before you conduct it. Further detail can be found here.

MHRA notification can be done at the same time you request ethics approval via the IRAS portal. Following approval from the MHRA, you will need to pay a fee and submit quarterly reports as your investigation progresses. There is a similar process in the US (with the FDA) for higher risk devices. 

After conducting your investigation, you need to document and discuss the results in a clinical investigation report. This is a detailed, accountable and traceable audit of all devices used in the study. As well as discussing the clinical findings, you should also discuss any adverse events and risks that arose. Remember, regulators care about safety and risk as much as performance. You should also indicate any findings you may need to further investigate, either pre- or post-market. 

Once again, ISO 14155 has helpful guidance and headings for content you will need to cover in your clinical investigation report. 

Post market surveillance plans need to clearly define:

Here, you need to document: 

PMS and PMCF can be combined into a single document - but all aspects must be covered! 

The clinical evaluation report is the pivotal document that regulators review when evaluating the clinical evidence for a medical device. This document can end up being quite long (sometimes over 100 pages), depending on how complicated the device is.  

The CER starts with a summary of the intended use, benefits and risks of the device. Then, it goes on to summarise and compile the clinical evidence from all steps of the clinical evaluation process: scientific, analytical, clinical validity (and in future updates, also post-market data).  

At the end of the document, manufacturers are expected to show how they meet the general safety and performance requirements laid out by the regulations, and how frequently they are going to update their CER and literature review.