In the loop22 January 2020
As technologies, power supplies, sensors and electronics evolve, so do the possibilities they bring. Closed-loop devices will likely be the enabler for real personalised medicine. Andrew Tunnicliffe talks with Robert W Gereau, vice-chair for research in the Anaesthesiology Department at Washington University, about his work and what the future holds for personalised medicine as the industry stands on the threshold of a device revolution.
Today, there is an entire generation of healthcare professionals with the concept of personalised medicine never being far from their minds. From the researchers and designers looking to develop the next breakthrough device or system, to the doctors and nurses caring for patients who themselves use the devices, technology has the potential to deliver personalised care, reshaping the healthcare landscape.
Since the concept was first uttered in the annals of medical literature 20 years ago, personalised care has grown in importance, at a pace with general technology itself. Its benefit is undisputable, providing individual patients with care and management regimens tailored to their needs.
From reducing the risk and need for more serious medical interventions for specific ailments, to cutting the cost of their healthcare, the significant advantages it brings are worthy of the ongoing investment it’s enjoying. According to Zion Market Research, the industry will be worth a staggering $3.4 billion by 2024, growing at an annual rate of almost 12% from the $1.57 billion in 2017.
“The biggest opportunities in my mind are for the implementation of closed-loop systems,” Robert W Gereau, vice-chair for research in the Anaesthesiology Department at Washington University, says. “That is, not just an implantable device that a patient and their physician can adjust over time, but a smart system that detects pathological changes in physiology and delivers a corrective stimulus in real time,” he continues.
The personalised care industry’s predicted value by 2024.
Zion Market Research
Dublin-based Medtronic is a leading developer of personalised medicine devices. In June 2019 it announced what it called a ‘pivotal trial’ for its Bluetooth-enabled MiniMed 780G advanced hybrid closed-loop system. The device aims to help improve overall glycaemic control in patients with type 1 diabetes. “Forgetting a pre-meal bolus can lead to hyperglycaemia and we recognise that as much as people try to remember to take a pre-meal bolus, or to accurately calculate their carbohydrates, real life sometimes gets in the way,” explains Robert Vigersky, chief medical officer for the Diabetes Group at Medtronic.
The company says a feasibility study had demonstrated the safety of the system, and its potential to improve overall glycaemic control and simplify diabetes management for individuals who forget to administer a bolus of insulin at mealtime, carb count inaccurately or choose to forgo announcing meals. It does this by monitoring and managing glucose levels, taking some of the responsibility from the patient and autonomously taking the measures needed to maintain levels.
The MiniMed 780G, intended for use by type 1 diabetes patients only, has the potential to dramatically advance the care patients receive and how their condition is managed. Clinical research into similar devices has also provided positive outcomes. In 2018, a study by the University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and Addenbrooke’s Hospital, revealed closed-loop devices significantly improved the time patients saw glucose in target range, between 3.9–10mmol/l, with the closed-loop group compared with the sensor pump arm.
Monitor in real time
However, it is not just in diabetes where significant steps are being taken. Closedloop therapeutic devices offer realtime, continuous monitoring, adjusting therapy as needed by the individual. They also allow carers to gain a better understanding of how a patient’s condition is managed and evolves over hours, days and weeks. This means doctors are better positioned to individually tailor treatments, cutting costs and improving health outcomes.
Gereau says pacemakers are a good early example of this, but advances since have been significant. “The advances in materials science around sensing various physiological parameters allow us to imagine a much broader application of this type of closed-loop system.”
The research team, including renowned materials scientist John Rogers, have been working with this technology for some time. He says one of these projects has been the development of an implantable device that provided on-demand drug delivery, combining wirelessly powered pumps that deliver drugs to a targeted tissue on demand via microfluidic channels. “While these devices were developed for preclinical research applications, there are a number of obvious potential clinical applications. We have also been conducting work to adapt these technologies for preclinical studies as proof of concept for potential clinical applications for things like pain relief, improvement of bladder control and other conditions.”
Researchers have developed a system that can detect changes in bladder contractions over time, indicative of an overactive bladder and automatically trigger activation of micro-LED devices implanted around the bladder to ontogenetically change the neural signals from the bladder to correct these pathological contractions.
This work also opens up possibilities for use in other fields. “For neuroscience, the rapidly developing world of massively parallel recording holds potential for more complicated scenarios,” Gereau says. “As we gain greater insight into neural circuit dysfunction associated with a host of brain diseases, there is the associated possibility to deliver targeted corrective therapies in a closed-loop fashion.”
These devices use multi-electrode arrays and amplifiers that are implanted, which record signals and have the potential to detect and take preventative action for seizures, for example. “A sensor could detect the onset of a seizure and automatically deliver a corrective stimulus,” Gereau explains. “This could be a number of different approaches from an electrical counter-stimulation to targeted delivery of a drug, to optogenetic inhibition of the affected brain region to quiet the seizure.”
The potential doesn’t stop there. “One could also deploy different sensors to detect changes in tissue oxygenation that could trigger a stimulus to correct the respiratory system, for example, associated with a drug overdose,” says Gereau. “Another is sensors that detect disrupted breathing during sleep that could help to reduce sleep apnoea.”
The use of devices like these is not without risk, raising privacy and security concerns. For some time now, those more distrustful of their use, in their current state at least, have questioned whether patient privacy could be an issue.
For Gereau, these issues are context specific. “For devices that help treat conditions that produce severe morbidity or mortality, it is difficult to imagine how there would be any moral issues,” Gereau says. “Things get much dicier when you imagine scenarios where brain interfacing devices might be used to ‘normalise’ behaviours.”
There are a lot of similar questions to wrestle with as technologies around AI, brain-machine interfaces and others advance put us in positions that could not be imagined a few years ago.
A BBC Panorama investigation, supported by media outlets around the world, warned of the risks posed by the growing use of medical devices, particularly as technology evolves. It found that patients were sometimes given devices not demonstrated to be safe in humans. Some had even failed during animal testing, yet were still being used.
Much of what was uncovered related to more traditional devices, the likes used for birth control or to help manage incontinence. However, questions were raised about the potential risks new technologies could pose. Speaking to the BBC, Professor Derek Alderson, president of the Royal College of Surgeons, warned that as devices advance, doctors could be less sure about their potential risk.
In response, the UK regulator, the Medicines and Healthcare products Regulatory Agency, issued a statement. “The need to protect public health, whilst not stifling innovation, must be carefully balanced,” the MHRA said. “The MHRA welcomes innovative medical devices that can bring huge health benefits to people as long as this doesn’t compromise patient safety.”
Challenges aside, the next generation of devices can help deliver on the promise of personalised medicine. Gereau is certain that, “The possibilities for closed-loop devices seem endless, and the advances in materials and powering schemes serve to bring them much closer to reality.”
Medtronic 2019 trial
What the trial is testing
This three-month pivotal trial will test the safety of the next-gen MiniMed 780G in people with type 1 diabetes. The MiniMed 780G will improve on several features of the current 670G hybrid closed-loop system, adding automatic correction boluses for high blood sugars, a time-in-range goal greater than 80%, an adjustable target glucose level of 100mg/dl (versus the current ‘less aggressive’ goal of 120mg/dl), Bluetooth connectivity (for remote monitoring, wireless data upload), pump software updating from home (in-warranty upgrades) and simplifying the ability to stay in Auto Mode (goal of 99% time spent in closed loop). Auto Mode is when the closed-loop system senses your glucose level and automatically adjusts basal insulin doses to bring you to towards the target glucose level.
What the trial is measuring
The trial will measure change in A1C and change in percent time in range (70–180mg/dL) over a three-month period. The study will also measure the number of instances of hypoglycaemia (less than 70mg/dl) and diabetic ketoacidosis.
Why is this new and important
As a pivotal trial, the results from this study will be submitted to the FDA to support approval of the 780G, which aims to launch by June 2020. The new 780G will be an additional option to Tandem’s upcoming Control-IQ system.
In a small study presented as a poster at the 2019 ADA Scientific Sessions, the MiniMed 780G was rated by 100% of 12 participants as the best device they had ever used. The 780G was shown to be safe, improve blood sugar and simplify diabetes management, even when users forgot to administer a bolus of insulin at mealtime or the carb counting was inaccurate.