Notified body official: Tell a product’s story when describing benefit-risk

ROTTERDAM, NETHERLANDS — When explaining a medical device's benefit-risk profile to a notified body, sponsors should consider what story they want to tell, says Richard Holborow, head of clinical compliance at BSI. In addition to the traditional factors, he said sponsors should also be able to describe the environment in which the product will be used and how it may affect patients and their caretakers.

“The first catchphrase of notified bodies is, ‘It depends.’ The second one is, ‘Tell the story,’” Holborow said.

“That's what we always want to understand,” he added. “Why do you have this device on the market? Where are the benefits?”

Holborow was part of a panel at the RAPS European Lifecycle Management conference, where he and other experts discussed what sponsors should consider when explaining benefit-risk profiles for products under the Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR). They provided several examples and walked the audience through their thought process in determining their benefit-risk profiles.

Holborow emphasized that sponsors should provide evidence that the product's benefits to patients are meaningful and measurable, as well as how the product helps patients manage their condition and its overall public health benefit. He used the example of a deep-brain stimulator to walk the attendees through his process for developing a benefit-risk profile, including assessing the magnitude of the product’s benefit, duration of benefit, probability of benefit, and key risks.

Deep-brain stimulators generally regulate brain activity to manage specific symptoms, such as treating Parkinson’s disease. They are also potential treatments for severe epilepsy, psychiatric conditions, and addiction.

Holborow noted that deep-brain stimulators to treat Parkinson’s disease may have a different risk profile than those used to treat dystonia and essential tremor, and sponsors should consider the risks of the device per indication. He noted that patients with Parkinson’s may have to go through two devices throughout their lifetime, but those with dystonia may have more than six, which increases their risk for infections each time they are implanted with a new device.

“If we're putting leads into different parts of the brain to manage symptoms, then there will be different risks that occur within that clinical or within that anatomical area that will be specific to the clinical condition,” said Holborow. “What this is trying to really illustrate is that even though we can say a device has a benefit-risk profile of X percentage or benefit-risk ratio, we really need to think of it from a patient and clinical condition level.”

Additionally, he said sponsors should consider how much risk patients and their caretakers are willing to accept with the device. In some cases, they may be willing to take more risks if that means they can potentially enjoy more quality time with their loved ones.

“What I'm trying to get across with this example is that each patient has their own individual story,” said Holborow. “The benefits and risks will be specific to them, their environment, and we need to think about that a little bit more when we consider benefit-risk.”

Holborow also listed several factors to consider as part of the overall benefit-risk assessment of a product that should also be considered with each indication. They include issues such as state of the art, side effects, invasiveness, whether the product is made from animal or human derivatives, whether it serves an unmet medical need, and the severity and probability of occurrence of the potential risks.

When conducting a qualitative benefit-risk assessment for multiple indications, Holborow recommended sponsors tailor their benefit descriptions to the clinical goals of each indication. He also said there are always contextual factors that sponsors should consider in their profile, such as the patient population, clinical setting, and operator needs.

“It's important that when you think about your clinical indications, that you're thinking about your benefit-risk, and you're thinking of it by stratifying the data for each of those indications,” said Holborow. “As we saw earlier, the data that supports dystonia will be very different to the data that is supporting Parkinson's disease, and we need to see that as a notified body.”

“Highlight the strength of evidence and certainties and gaps per use case,” he added. “Be honest with us. We know that gaps will exist in your data, but that's what [postmarket clinical follow-up (PMCF)] is all about.”

Holborow emphasized that sponsors should consider their PMCF plans based on their product's benefit-risk assessments. Finally, he recommended that sponsors use expert judgment, such as that of clinicians, to interpret benefit-risk across indications.

“Clinicians are great. This is something they do every day,” he said. “Work with your clinicians… Get that information in there to really drive your benefit-risk statement.”

Holborow also noted that getting patient input on the benefit-risk profile is critical.

“The true experts of any benefit-risk are really our patients,” he added. “They are the individuals who are willing to compromise certain risks to gain certain benefits.”

Notified body official: Tell a product’s story when describing benefit-risk

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