A Franklyn Health × Mantra Systems Perspective

This article was written by Dr Will Brambley, a Lead Medical Writer at Mantra Systems. Mantra Systems is a medical device regulatory consultancy company, specialising in regulatory affairs and other essential market access activities, including supporting medical device manufacturers achieve UKCA & CE-marking.

The state-of-the-art (SOTA) literature review is a key component of a Clinical Evaluation. It tells you everything you need to know about the clinical field in which your device will operate, and the current gold standards for treatment in this area. All too often, the SOTA is conducted in the weeks and months leading up to the submission of the technical file.

This can lead to a mismatch between the outputs of the SOTA and the clinical evidence presented for a device. Performing a SOTA review in the early stages of device development not only avoids this risk but can also focus device development and guide clinical evidence generating activities.

What is the purpose of the SOTA?

The SOTA review has three main aims:

  • To place your device into clinical context by outlining the intended use, the target clinical conditions, and describing how it achieves its therapeutic benefit. 
  • To review and quantify the performance and safety of SOTA devices to identify the current clinical landscape and how similar devices are evaluated. 
  • To develop safety and performance objectives, to provide measurable benchmarks against which your device will be compared in your Clinical Evaluation Report (CER). 

Although it is a key component of your EU or UK MDR technical file, you don’t need to have a completely fleshed out device to conduct your SOTA. Most of the information you need is in your possession at the conceptional stage of device development. You can use this information to define the scope of the SOTA and begin finding the rock-solid evidence on which to base future decisions. 

 

The scope of the SOTA

The best way to define the scope of your SOTA is to develop research questions which help to guide search term selection. In short, research questions outline what you intend to discover from the literature review. 

I’d recommend using a PICO framework to help with this process. PICO is used extensively in evidence-based clinical practice and is also recommended in MedDev 2.7/1 rev 4 guidance. PICO specifies four concepts: 

  • Patient issue or Population 
  • Intervention 
  • Comparison 
  • Outcomes 

You can use your knowledge of your device and how it will be used to develop research questions which can be translated into search terms for scientific literature databases. You do not need to know exactly how your device will be manufactured, or the exact software architecture, in order to scope your SOTA and conduct the literature search.  

 

Performing a SOTA early on can help device development

  • The essential needs of users in your clinical field. 
  • What features and functionality current SOTA devices have. 
  • What the common adverse events or complications are that should be addressed by a new solution. 

As it is evidence-based, the SOTA can inform your design decisions from a position of authority. It provides investors and stakeholders in your product with confidence that it solves a meaningful problem and will have commercial viability.  

You can not only use the SOTA to optimise the performance of your device, but also to improve its safety profile. Knowing the current failure modes and complications of SOTA devices means that you can alter your design to minimise these risks, or even eliminate them entirely. 

 

Performing a SOTA early

This can help build a Clinical Evidence Strategy

The SOTA doesn’t just tell you how SOTA devices are performing. It also tells you exactly what clinical evidence you need to generate in order to secure regulatory approval and ultimately market access.

Let’s imagine that you are developing a novel hip implant to treat patients with osteoarthritis. You have conducted a SOTA review and have found that SOTA devices: 

  • Improved reported pain on a Visual Analogue Scale (VAS) by a mean value of 2.4. 
  • Had a mean procedural infection rate of 1.3%. 
  • Had a mean dislocation rate of 2.2% over a 10-year period. 

In terms of your Clinical Evidence Strategy, this tells us three key things: 

  • You will need to prove non-inferiority to these objectives in your CER by comparing your own evidence to the SOTA benchmarks. 
  • When gathering clinical data about your device, you will need to ensure you are measuring the same or comparable outcomes to the SOTA in order to make this comparison. In this case that means gathering data on pain VAS outcomes and infection rates. 

When planning a clinical trial to generate evidence for your device, an early SOTA review can tell you exactly what you need to look for and how you need to structure your trial. This will lead to regulatory success as well as ensuring maximum return in value from a clinical trial.  

 

The risks of conducting a SOTA late in the regulatory process

While we’ve discussed the benefits of doing your SOTA review early, it is also important to consider the risks of completing it late in the process.

Manufacturers that begin their SOTA late can have the following problems:

 

  • Gaps in your clinical evidence meaning you must limit your clinical claims and benefits. 
  • The need for additional costly clinical investigations. 
  • Using data from equivalent devices to fill holes in your clinical evaluation, which increases regulatory scrutiny. 
  • Notified Bodies finding non-conformities with your clinical evidence, leading to multiple rounds of review. 

This is why working with an experienced CRO and regulatory consultancy can streamline your clinical evidence strategy and ultimately bring your device to market quicker and at a lower cost. 

 

The importance of a SOTA

The power of an early SOTA is that it tells you what clinical evidence you need and what the potential strengths and weaknesses of your device are. This gives you powerful strategic tools to optimise device concepts and design, plan effective clinical investigations and ensure regulatory success. 

This is why we’re so happy to partner with our friends at Franklyn Health. They can offer device-focused clinical study design, startup, and management and we’re able to provide a SOTA that works for you first time. Get in touch with us now and let’s remove your regulatory worries together.