Top 3 Reasons Why Your Medical Device Needs a Clinical Trial

Regulations for research involving devices, in vitro diagnostics (IVDs), and digital therapeutics differ from those governing pharmaceutical development. While drugs require Phase I-III clinical trials—and are also subject to post-approval tracking—digital therapeutics, devices, and IVDs may be able to leverage bench testing, animal studies, pilot studies, and training sets. These are usually followed by validation studies, pivotal trials, literature reviews, and even real-world evidence studies, depending on the individual product’s intended purpose and the risk level.  

Medical devices, IVDs, and digital therapeutics have the potential to bring significant health benefits to patients of every age group, including healthy populations and those with varying severity of health ailments and disease burdens. Interpreting evolving regulations for these devices is often a unique challenge for emerging biotech companies. Staying on top of evolving regulatory requirements for a complex medical device category can be overwhelming, even for well-established life science companies.  

How do you determine if clinical trials are needed for your device? Here are some ways to decide if clinical trials are necessary and navigate the compliance intricacies of a complex medical device category.  

Function Dictates Regulation 

It’s essential to understand how the product interacts with a patient, as well as what level of importance it holds to the patient’s health. In other words, what are the risks and benefits of the product? The greater the risk, the more likely a series of trials for market clearance or approval will be required. 

In the United States, a medical device, IVD, or digital therapeutic is categorized as one of the following: 

• Class 1: Non-invasive, low risk to the patient, and subject only to “general controls” around registration, branding, and labeling. 
• Class 2: Products posing a higher risk to the patient; most products in this category require a 501(k) premarket notification, meaning a detailed comparison to a device already in market.  
• Class 3: Applied to products with the highest risk, or to Class 2 products that are the first in their category. These products will require clinical trial data to get to market, but with significantly fewer participants required as compared to a drug trial. 

Intended Use, Indication, and Mode of Action 

Intended use and indication for use are often confused or thought of as the same. Think of the intent or purpose for the intended use (e.g., what the device does) and the indication for use is the patient population, disease, condition, and duration of use. Additionally, consider intended users and the environment of use. These claims are those made on the product labeling, and they need to be successfully demonstrated in the clinical evidence. 

Consider three examples to determine your path: a tiny camera the patient swallows to take internal photos, a new blood test designed to indicate monkeypox, or a mobile device application monitoring a patient’s A1C levels.  

The indication follows the intended use, but it also places the product in the context of a disease/medical condition. It’s important to bear in mind the indication can change the product’s risk level. In the example above, the camera diagnoses intestinal disorders, the blood test diagnoses suspected infection, and the mobile medical app (MMA) supports patients with diabetes types 1 and 2.  

Finally, what is the product’s mechanism of action or mode of action (MoA), especially as it relates to patient interactions? Thinking about whether the product is invasive, non-invasive, significant, or non-significant risk, and how it operates inside or outside of the patient is crucial. This is how the product achieves its therapeutic effect. For instance, a harmonic scalpel vibrates as it cuts, a COVID-19 test detects SARS-CoV-2 antibodies by measuring antigens in a person’s saliva/mucus, and a digital therapeutic program electronically signals how or when a patient should adhere to best practices or adopt a positive-reinforced behavior.   

Gather and Publish the Evidence  

A comprehensive clinical evidence generation plan determines what critical data is needed as evidence indicating the product does what it is supposed to do safely. Some markets – specifically the EU – may require publication to obtain product approval. 

Most critical is understanding what kind of study to conduct. To find this answer, return to the type of product and its risk level to determine if a trial is required, and if so, what kind. Types of trials include:  

• Pilot or feasibility: small study to collect safety results, proves a concept and can guide future study design 
• Verification studies (training set): smaller studies designed to test a device or train an algorithm prior to design freeze 
• Validation studies: larger studies designed to support the efficacy and safety – or sensitivity and specificity – of certain devices and/or algorithms claimed 
• Demonstration of Equivalence: EU distinction for literature and other comparative evidence against an existing product’s performance 
• In silico: Studies designed to simulate data without testing in humans 
• Pivotal: Large, statistically driven study to confirm efficacy, safety, and risk-benefit 
• Real-world evidence (RWE): Data is collected from real-world sources, including registries, electronic health records, administrative claims, etc. 
• Post-market safety: usually in support of obligations after clearance or approval 
• Human factors: to inform ease of use, features, labeling, and instructions by end users 

Stay focused on the future of the product after approval, when indications for other conditions may be added or the design of the product is adjusted. Approval may be the immediate goal, but it is likely not the product’s final goal.  

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