Common questions when bringing a medical device to the market for the first time
There are many challenges to face when bringing a medical device to the market for the first time. In this article, we will present and answer the most common questions we get from those conducting a clinical evaluation and bringing a device to the market for the first time to provide an overview of some of the activities you will have to perform.
What is a clinical evaluation and why do I need it?
Clinical evaluation is a part of the technical documentation needed for CE-marking. You cannot obtain a CE-marking without a clinical evaluation and it is a requirement for all classes of devices. But it does not stop there. Once you have your CE-mark you must update the clinical evaluation, providing new data that confirms safety and performance. The reason for this is to make sure that your product is still safe and performing as intended when used in the broader population.
Clinical evaluation is defined by the Medical Device Regulation(MDR) as a systematic and planned process to continuously generate, collect, analyse, and assess the clinical data pertaining to a device to verify the safety and performance, including clinical benefits of the device when used as intended by the manufacturer.
But what does this mean for you?
The clinical evaluation process is systematic and planned; meaning there is a specific timeline in place for actions and procedures to support those actions, all so you can implement the process into your normal developmental procedures. First, you need to describe how you generate, collect, analyse and assess the clinical data. All the datapoints need to be addressed specifically throughout your clinical evaluation plan and report. Meaning that you must connect the data to the specific product safety and performance objectives and have a thread between your data and what it proves. This is very important and one of the most common mistakes is forgetting to relate the objectives with the actual found clinical data to the safety and performance requirements.
When writing your clinical evaluation, you will need to define what it is you are claiming about your product, how it performs and what the safety criteria is. After this, you shall identify and determine equivalent devices (if applicable) to establish if there is any clinical data available associated with those equivalent devices that you can use within your evaluation. And then you should be able to determine which clinical data you still need to generate and how to collect these.
What are my clinical benefits, safety, and performance objectives?
The safety and performance requirement that you need to fulfil using clinical data can be found in the GSPR (General Safety & Performance Requirements) checklist and is a key document in the development process of a medical device. You will connect your safety and performance requirements within the analysis of your clinical data. Clinical benefit means the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health. The clinical benefits can also be the company clinical product claim, these are usually statements in your promotional or sales material. The statements are also specified by the manufacturer in the clinical evaluation. In general, safety and performance objectives and clinical benefits are all measurable, meaning that they can be put up using numbers. The clinical benefits and safety and performance objectives can all be proven by demonstrating equivalence to a predicate product if applicable and data are available.
Which brings us to the next question:
How do I prove equivalence?
The equivalence pathway allows the manufacturer of a medical device to use the technical documentation, post-market surveillance (PMS), post-market clinical follow-up (PMCF) and the scientific literature related to an already marketed device. Thereby avoiding the time and cost for performing clinical studies to fulfil the safety and performance requirements as defined in the clinical evaluation.
Proving equivalence was earlier established under the Medical Device Directive. You were able to use the literature route and take advantage of data from similar devices and compare them with the manufacture’s own product. Today, proving equivalence is a difficult process and is only possible if you as a company have an equivalent product or have a contract in place where they have access to the technical documentation (class III and class IIb implants) of that equivalent product. If you can get access to the technical documentation needed for proving equivalence, you must present technical, biological, and clinical similarities to the extent that there would be no clinically significant difference in the safety and clinical performance between the two devices.
How do I get started on my benefit-risk analysis?
As part of the clinical evaluation process your clinical benefits/claims must be defined. The benefits/claims are part of your benefit risk assessment. If you have not defined them yet, it is time to sit down with your team, both developers, clinical, regulatory and sales/marketing people, and address what you want to state about your product and what data is needed to fulfil the clinical related claims.
Your identified clinical benefits should be measurable, and you should be very clear in the references and data that documents your benefits and then relate this to the state of the art and medical standard of care treatment. The overall purpose of the benefit-risk analysis is to prove that the measurable benefit(s) outweigh the clinical risk(s). Your benefits can be analysed by the the following parameters:
- Types of benefits
- Magnitude of benefit
- Likelihood of experiencing one or more benefits
- Duration of effects
- Patients’ perspective on benefit
- Benefit factors for health care professionals or caregivers
- Medical necessity compared to what is currently available
Those factors must be greater than the severity, number, rate, probability, and duration of expected harmful events.
Use this as a tool to identify if you are missing specific data and if you need to find this in a clinical investigation.
How do I start a clinical investigation?
A clinical investigation is set up to verify the expected clinical benefits, safety, and performance of your product. The background for implementation and design of a clinical investigation should be based on a review of relevant literature, pre-clinical documentation, and the identified clinical risks. Remember that your clinical study must be clinically relevant, achieved by scientific principles and support the purpose of the medical device.
The first thing to do before initiating the clinical investigation, is to create a study team for the planning and the completion of the investigation. Your team members must have documented training/expertise within the area.
Next, you must have the following documentation in place:
- Clinical Investigation Plan – CIP
- Investigator’s Brochure – IB
- Case Report Forms
- Subject Information
- Informed Consent
- Letter of Authority
- Approvals/Authorisations – Ethics Committee/Competent Authority, Data Protection Agency
- Contracts with the hospital and other stakeholders
- Monitoring Plan
- Statistical Analysis Plan
- Quality System procedures for conducting clinical investigations.
Before initiating the clinical study, you must lock the design of the product and finalise your verification and validation testing except for the datapoints that can only be collected during the clinical study. Finally, the products to be used in the clinical study can be produced during the manufacturing validation process.
At the Site Initiation visit required before the first patient being enrolled in the study the site study staff should be trained in the use of the device and the study protocol.
Besides, ensuring safety of the patient compliance and documented study oversight is key to achieve a successful study outcome. Time and resources should be set aside for monitoring and quality assurance during the study.
The development of devices is complex and insight to several different regulations and guidelines are needed. We hope that the above text has given some insight from a practical standpoint on how to go from an idea to actual collection of patient data.
Norway Health Tech has launched a clinical evaluation and assessment training series in collaboration with Qmed Academy. The series consist of 4 training courses in clinical evaluation, benefit-risk assessment, and clinical investigation. You can find them here: https://www.norwayhealthtech.com/event/
Upcoming courses with Qmed Consulting A/S
This article is written & edited by Qmed Consulting1 in collaboration with Norway Health Tech2
1 Helene Quie, CEO, Qmed Consulting
1 Josefine Wulff, Qmed Consulting
2 Kami Faust, Regulatory Advisor, Norway Health Tech
2 Chalisse Fortson, Norway Health Tech