As DIY ‘loopers’ reinvent artificial pancreas, endocrinologists confront safety, liability concerns

The FDA approval of the first hybrid closed-loop insulin delivery system for type 1 diabetes in November 2016 ushered in a new era in diabetes technology — one that promises novel therapeutic options that can improve outcomes, reduce disease burden and improve quality of life.

For some, that pace has not been fast enough.

A person with diabetes who wants to build a do-it-yourself, closed-loop insulin delivery system, also known as an artificial pancreas, already has access to the information needed to create the automated system on their own. “Loopers,” as DIY artificial pancreas builders have become known, are a growing online community of savvy, engaged patients and parents who are “hacking” older insulin pumps to build the technology they say they will no longer wait for — a closed-loop insulin delivery system that is fully customizable.

“First we have to keep the big picture in mind: It’s not going to move the needle in terms of getting millions of people to use this particular system, but it’s serving an important role by creating awareness that the technology is available now,” Jeremy Hodson Pettus, MD, an endocrinologist and associate professor of medicine at the University of California San Diego School of Medicine, who recently built his own DIY system, told Endocrine Today. “It is time to be aware of it, and it is time to be prepared. Type 1 diabetes is about to change dramatically. I’ve seen firsthand how these systems can improve glucose control, reduce rates of hypoglycemia and make significant improvements in quality of life. When these improvements can happen now, it’s really no wonder that patients are seeking out this solution.”

Currently, more than 1,000 patients have opted to build homemade artificial pancreas devices, relying not on health care providers, but on a growing online community that provides detailed instructions and real-time help.

Source: University of California, San Diego. Printed with permission.

But with new technology come new concerns. Some endocrinologists and diabetes educators are reluctant to manage patients hacking old devices to create systems that are not regulated or FDA approved. That can leave some people with diabetes without a provider who wants to work with them.

“The DIY system points to a real need for people to have access to things like this,” Bruce A. Buckingham, MD, professor of pediatrics and endocrinology at Stanford Children’s Health Center, Stanford University, told Endocrine Today. “It’s designed by users, for users, so they’ve really been working on the interface and on how they would like to see things. ... The systems developed by companies are often developed by engineers on a desktop. This is designed by the people wearing it.”

#wearenotwaiting

There are several quality-of-life factors driving the move to a DIY closed-loop system, Brenda Weedman, MS, BSN, RN, CDE, lead nurse for the Vanderbilt Diabetes Center’s Pump and Device Clinic at Vanderbilt University Medical Center, said during a presentation at the American Association of Diabetes Educators annual meeting in August. Those factors include reports of improved sleep, which is the No. 1 community-reported benefit, reduced anxiety and frustration, reduced disease management burden, improved HbA1c and increased time in glucose range, she said.

The hashtag #wearenotwaiting, Weedman said, has become the rallying cry of people in the diabetes community who have developed platforms, apps and cloud-based solutions, reverse-engineering existing products to improve diabetes outcomes. Interested patients who want to build their own DIY system typically find their way to community Facebook groups that offer virtual support, including Looped, CGM in the Cloud, xDripG5, and Nightscout for Medtronic.

Weedman, who has lived with type 1 diabetes for 35 years, said the DIY “OpenAPS” system has given her peace of mind since she and her husband built it together over Labor Day weekend 2017.

“These systems don’t get tired,” Weedman said. “I wake up at 120 mg/dL every single morning. Talk about starting your day off well. I haven’t experienced that since my diagnosis until I started doing this.”

Many DIY adopters, Weedman said, had no previous technical experience.

The community, she said, is self-supported through a 24-hour, global online support group, as well as a “strong safety message” and guidance to assist new adopters.

“Somewhere in the world, there is a looper who is awake and is willing to help you,” Weedman said.

Basic system components of the DIY closed-loop system include the following:

• Medtronic insulin pump built before 2010 (U.S.), Dana RS (Sooil Development) or Accu-Check Combo (outside U.S.);
• microcomputer or iOS app that issues commands to enact a temporary basal rate;
• communication circuit board (Riley Link, Explorer Board);
• continuous glucose monitor, such as Dexcom, Enlite (Medtronic) or the Freestyle Libre (Abbott); and
• monitoring device, such as a smartphone or smartwatch.

The DIY landscape includes three systems to date, including OpenAPS, Loop and the AndroidAPS, which is primarily used in Europe.

“I can’t tell you why the math is better, but the algorithms for adjusting insulin dosing with DIY seem less constrained,” Anne L. Peters, MD, professor of clinical medicine at Keck School of Medicine at the University of Southern California, Los Angeles, told Endocrine Today. “My select patients who use the DIY system often have much better blood sugars and HbA1c, with more time in range, less variability and less hypoglycemia — they appear to reach and maintain their targets more easily than with other systems, once they put in the time to set it up.”

Pettus, who was diagnosed with type 1 diabetes at age 15 years, received an old Medtronic pump from a patient a little more than a year ago. Today, he is using Loop.

“The main benefit for me is overnight,” Pettus said. “It’s just so nice to go to bed and not have to worry about your blood sugar. I don’t get low at night. I don’t wake up sweaty. I feel safer. I sleep better.”

The steps to build your own system, although not tedious, are complicated, especially for a nonsavvy tech user, Pettus said.

“All of these steps patients have to take are definitely hoops,” Pettus said. “The upside is that somebody is not just going to accidentally stumble upon this system and start using it. This legwork is almost a built-in safety mechanism.”

Cautious support

Medtronic, for its part, has offered cautious support for the growing DIY movement; however, officially, the company discourages the use of older pumps for off-label indications.

“Medtronic admires the passion of the DIY community and shares their commitment to improving the quality of life for people with diabetes,” Francine Kaufman, MD, a former president of the American Diabetes Association and chief medical officer for the diabetes group at Medtronic, told Endocrine Today. “That is why we strongly discourage intentional device modifications of our insulin pump systems and the public sharing of therapy delivery hacks, as this can adversely impact device performance and potentially put patient safety at risk.”

Kaufman said Medtronic will continue to partner with health care providers, patients, advocacy organizations and the FDA for further advancements on the path to a fully automated, closed-loop insulin delivery system.

Meaningful improvements

In a retrospective crossover study published in Diabetes in June, Dana M. Lewis, a founder of the DIY artificial pancreas movement, and colleagues from the Johns Hopkins Diabetes Center analyzed outcomes from a subset (n = 20) of the DIY closed-loop community, comparing mean blood glucose, time in range, and time spent above and below clinically meaningful thresholds before and after initiating the OpenAPS system.

The researchers assessed continuous blood glucose readings recorded during 2-week segments 4 to 6 weeks before and after initiation of OpenAPS, as well as mean blood glucose and time in range during the day, overnight and overall.

The researchers found that mean blood glucose and time in range improved in every time category. Mean blood glucose fell from 135.7 mg/dL to 128.3 mg/dL, mean estimated HbA1c fell from 6.4% to 6.1%, whereas time in range increased from 75.8% to 82.2% overall.

Overnight, time spent in hypoglycemia fell from a mean of 6.4% to 4.2%; time spent below 50 mg/dL fell from a mean of 2.3% to 1%.

Safety, liability concerns

Despite reports of impressive numbers and improved outcomes, some experts caution there can be risks that come with the use of open-source algorithms for medical devices like the artificial pancreas.

“One of the challenges with these complex systems is that patients may not fully understand how these devices are designed to work, nor do they understand the limitations of these systems,” Courtney H. Lias, PhD, director of the division of chemistry and toxicology devices in the Office of In Vitro Diagnostics and Radiological Health at FDA, told Endocrine Today. “In addition, these DIY systems have not been systematically evaluated or designed in a quality system, so the failure modes are not all identified. That makes it difficult for patients to understand the likelihood of potential risks for their treatment, such as inappropriate dosing from the automated algorithm, or compatibility — or lack of — with other medications they may be taking.”

Malfunctions or misuse of automated insulin delivery systems can lead to acute complications of hypoglycemia and hyperglycemia that may result in serious injury or death, Lias said.

“The FDA provides independent review of complex systems to assess the safety of these nontransparent devices, so that users do not have to be software/hardware designers to get the medical devices they need,” Lias said.

The use of open-source algorithms with commercially available devices also raises legal questions, according to experts. In a commentary published in August in the Journal of Diabetes Science & Technology, Katharine D. Barnard, PhD, professor and health psychologist at Bournemouth University, United Kingdom, and colleagues noted that regulatory burden for new devices can ensure a higher level of safety as well as a certain degree of protection from legal action for the manufacturer and the prescriber. However, questions of liability also need to be answered for physicians, particularly if they are employed by a hospital, when they treat patients using a DIY closed-loop system.

“As an analogy, the hypothetical case of a physician ‘prescribing’ a patient treatment using an unauthorized drug ... is a clear-cut violation of the law,” Barnard and colleagues wrote. “Similarly, if an endocrinologist or other health care provider gives therapy recommendations to a patient who uses a DIY [artificial pancreas system], knowing that these systems are unregulated, they could become liable.”

Additionally, if a third party, such as a parent, caregiver or partner, sets up a DIY system for someone else, the setup no longer becomes “DIY,” they wrote.

“In that case, the third person could become liable,” Barnard and colleagues wrote. “It must be clear whether it is the decision of the person with diabetes or third person to use the DIY [artificial pancreas system] and whether the full understanding of core issues is held by both parties.”

Pettus said providers should keep an open mind and be ready to offer some guidance to patients.

“My No. 1 fear, and what I have heard anecdotally, is that sometimes people tell their endocrinologist that they are interested or maybe already started on DIY, and their endocrinologist is fearful that they may be liable and will actively deter their patients from trying it or tell them to stop using it,” Pettus said.

The backdrop to that, Pettus said, is that clinical evidence is needed.

“We need more outcomes, one, that demonstrate that this is safe, and two, that it is efficacious,” Pettus said.

Message for providers

Providers should recognize that patients using a DIY system are doing so off-label, just like the use of any FDA-approved drug for a nonapproved indication, Peters said.

“The pump is FDA-approved and the sensor is FDA-approved — it’s the algorithm that is not FDA-approved,” Peters said. “If a person is capable of learning this system, they should be supported; however, I also think that if you, as a provider, think that the person isn’t using it appropriately, then the recommendation should be to stop it.”

If a provider is not comfortable working with the DIY system, the provider should refer the patient to another endocrinologist who is, Peters said.

“It’s always about supporting the patient,” she said. “No matter what your level of knowledge is about this system, you always have to ask, ‘Do you have backup insulin? Do you have glucagon for when you go low?’ The nuts and bolts of how you keep a person with type 1 diabetes safe is all about being prepared. That’s the bread and butter of type 1.”

Osama Hamdy, MD, PhD, FACE, medical director of the Obesity Clinical Program at Joslin Diabetes Center and associate professor of medicine at Harvard Medical School, said he does not advise his patients build a DIY system; however, his patients know he will continue to see them and work with them to set targets.

“I, mostly, behave like a parent who sees his kids getting the life experience and observe them and sometimes guide them so as not to get harmed, but don’t stop them,” Hamdy told Endocrine Today. “Patients are using CGM as part of their system, and this gives many safety signals anyway.”

“Most of the DIY patients are so sophisticated in order to build the system with an out-of-warranty pump,” he added. “They come to me to get the blessing of the endocrinologist and check their HbA1c. They share their data, which are really impressive. The patients that I have on DIY closed loop have an HbA1c between 5.5% and 6.5% with nearly no lows, which surprised me.”

Pettus said the endocrinologist might feel a bit removed from the conversation when a patient is taking on building their own closed-loop insulin delivery device, but it is more important than ever that the provider stay actively involved.

“There is this tendency, as a doctor, to feel like you should know everything,” Pettus said. “Some providers might need to ask, ‘Can I adjust the targets? What can I still do here?’ They could throw up their hands and say, ‘You’re on your own.’ But definitely, targets still need to be adjusted. If it loses the signal, it reverts back to its basal rates.”

Future of DIY

Lias said the FDA is working to speed up the availability of therapies like automated insulin delivery. The 670G closed-loop system was approved a full 3 years earlier than Medtronic expected, with rapid approval in 103 days. That quicker pace was no accident. It followed monthly meetings between the agency and the manufacturer for 2 years to ensure an efficient regulatory review of the device and its clinical data.

“Patients with diabetes deserve to feel like they do not have to resort to using unapproved DIY devices to get the help they feel they need,” Lias said. “To that end, we have been working to speed up the availability of these important therapies. We succeeded in speeding up the availability of the first approved system, and we are also working on novel regulatory pathways to speed up the availability of more approved automated insulin delivery systems.”

For Peters, the home-built closed-loop systems point to an even better future for people with diabetes.

“This system gives me hope because I see these algorithms working so much better than other algorithms,” Peters said. “For me, it makes me say, ‘Look what is possible.’ Look what the FDA can approve, and look at what we are aiming for. We need to be open to this.” – by Regina Schaffer

• References:
• Barnard KD, et al. J Diabetes Sci Technol. 2018; doi:10.1177/1932296818792577.
• Farrington C. Lancet Diabetes Endocrinol. 2018;doi:10.1016/S2213-8587(17)30411-4.
• Lewis DM, et al. Diabetes. 2018;doi:10.2337/db18-352-OR.

• For more information:
• Bruce Buckingham, MD, can be reached at Stanford University, Department of Pediatrics – Endocrinology, 780 Welch Road, Room CJ 320H, Palo Alto, CA 94305; email: buckingham@ stanford.edu.
• Osama Hamdy, MD, PhD, FACE, can be reached at Joslin Diabetes Center, One Joslin Place, Boston, MA 02215; email: osama.hamdy@joslin.harvard.edu.
• Francine Kaufman, MD, can be reached at Medtronic Diabetes, 18000 Devonshire St., Northridge, CA 91325; email: fkaufman@ chla.usc.edu.
• Courtney H. Lias, PhD, can be reached at the Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993.
• Anne L. Peters, MD, can be reached at the USC Clinical Diabetes Program, 150 N. Robertson Blvd., Suite #210, Beverly Hills, CA 90211-2142; email: annepete@med.use.edu.
• Jeremy H. Pettus, MD, can be reached at the University of California, San Diego, Clinical and Translational Research Institute, 9452 Medical Center Drive, L1W-515, La Jolla, CA 92037.

Disclosures: Buckingham reports he receives research funding from Dexcom, Helmsley Foundation, Insulet, Medtronic and Tandem, and is an advisory board member for ConvaTec and Novo Nordisk. Hamdy reports he has received research grant support from the National Dairy Council; has served on the advisory council for AstraZeneca; has consulted for Abbott Nutrition, Merck and Sanofi Aventis; and is a shareholder for Healthimation LLC. Kaufman reports she is chief medical officer for the Diabetes Group at Medtronic. Lias reports she is the director of the Division of Chemistry and Toxicology Devices in the office of In Vitro Diagnostics and Radiological Health at the FDA. Peters reports various financial ties with Abbott, Becton Dickinson, Bigfoot, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Lexicon, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, Sanofi and Science 37. Pettus reports he consults for Dexcom, Diasome, Mannkind, Novo Nordisk and Sanofi.