In this final report, we have compiled our full coverage from the EASD Diabetes Technology Meeting 2015 held in Dusseldorf, Germany from February 11-12. This small 1.5-day meeting of ~120 attendees was mainly focused on regulatory approval of devices in Europe, though talks also touched upon the artificial pancreas and the EU reimbursement environment. Despite the conference’s intimate size and brevity, organizers did a tremendous job in recruiting many big names in the field — the agenda was p-a-c-k-e-d! We were treated to talks from top-level executives at the EU Commission and big thinkers on reimbursement from three of the largest markets in Europe, not to mention EASD President Dr. Andrew Boulton and ADA Chief Scientific and Medical Officer Dr. Robert Ratner. Below, you will find several of our top highlights from the meeting, followed by detailed write-ups. Titles of some of the most notable talks are highlighted in yellow.
1. Dr. Lutz Heinemann (Science & Co., Düsseldorf, Germany) presented the long-awaited ADA/EASD Position Statement on Insulin Pumps, now published online in Diabetes Care and Diabetologia. The document emphasizes the need for the FDA and EU to take a more active role in device oversight, with a particular focus on infusion sets, more thorough education of users/HCPs, and more standardized manufacturing and reporting requirements.
2. ADA Chief Scientific & Medical Officer Dr. Robert Ratner provided a strikingly positive appraisal of the FDA’s recent efforts on the diabetes device regulatory front. His optimism was tempered by a more critical take on the current state of interoperability – “The reality is that if you don’t have access to data, you have no choice and it serves no purpose.”
3. The EU Commission’s Mr. Erik Hansson provided a valuable overview of the state of play in EU negotiations to tighten the medical device regulatory approval process. He acknowledged that a centralized European agency for devices would offer a compelling a solution to the fragmented ecosystem of notified bodies, but unfortunately, this is politically unlikely.
4. Ms. Kelly Close (The diaTribe Foundation, San Francisco, CA) discussed the future of diabetes care in a digital era, placing the high enthusiasm for its potential into the context of ongoing and future challenges. She noted that it’s still early “1.0” days in digital health and technology brings encouraging upside to change diabetes care delivery.
5. Dr. Steven Russell’s (MGH, Boston, MA) comprehensive overview of the Bionic Pancreas shared an updated timeline on commercialization – now “2018,” a bit back of the longstanding goal to bring it to market by 2017 due to a major NIH funding opportunity and the additional requirements for chronic glucagon exposure.
Honorable Mentions: On reimbursement, we received updates from three of the largest markets in Europe: Germany, France, and the UK. We delve into detail below …
- Executive Highlights
- Detailed Discussion and Commentary
- Welcome Address
- Experiences from Other Associations
- The Bionic Pancreas – A Dawn of Hope
- Medical Devices in Europe – Emerging Political Issues
- The Strengthening of the EU Medical Devices Regulatory System
- Medical Devices
- The New MDD/IVD regulations
- The Role of MedTech Europe – A View Beyond Regulations
- Reimbursement for Medical Devices in Europe
- What Makes a Diabetes Device Worth Spending NHS Monies? Experience From the UK
- Reimbursement for Medical Devices in France through HAS and ANSM
- Reimbursement of Continuous Glucose Monitoring (CGM) in Germany
Detailed Discussion and Commentary
Andrew Boulton, MD (President, EASD, Manchester, UK)
Dr. Andrew Boulton opened the meeting with an urgent call to action – “Our technological powers increase, but the side effects and potential hazards also escalate. That is our raison d'être today.” Dr. Boulton reprised many of his criticisms of the CE Mark process that we have heard in the past (EASD 2013, EASD Diabetes Technology 2014): the competing interests of notified bodies, the lack of pre- and post-market data, and the very complicated and bureaucratic EU regulatory and lawmaking process. Indeed, with increasingly complex technologies on the horizon, Dr. Boulton shared concerns that closed-loop systems (if not properly vetted) have the potential to be just as dangerous as dosing insulin itself. We would agree that patient safety is absolutely top of mind, and the challenge rests on the proper balance between gathering lots of pre-market data and getting devices to market in a timely fashion.
ADA/EASD Statement on the Evaluation of Insulin Pumps
Lutz Heinemann, PhD (Science & Co., Düsseldorf, Germany)
Dr. Lutz Heinemann presented the long-awaited ADA/EASD Position Statement on Insulin Pumps, now published online in Diabetes Care and Diabetologia. Described in detail below, the paper was motivated by a desire for more pre- and post-marketing surveillance and a need for a more systematic and transparent regulatory process. Dr. Heinemann emphasized the need for both the FDA and EU to take a more active role in device oversight, noting that the loopholes that plague the EU system of separate Notified Bodies are in especially great need of attention. Highlights of the guidance include an emphasis on attention to the pump apparatus as a whole (including the infusion set), more thorough education of users and healthcare professionals, and more communication between international regulatory bodies to develop standardized requirements.
- Dr. Heinemann opened his presentation by highlighting many of the shortcomings of the FDA and EU regulatory systems for insulin pumps. These were not surprising and summarized many of the limitations we have heard previously: the misaligned incentive structure of the EU system of Notified Bodies, a lack of standardized adverse event reporting, no oversight of infusion sets, inadequate registries, etc.
- However, we were intrigued to hear Dr. Heinemann also identify inadequate patient education as an existing problem in the pump regulatory ecosystem. He noted that the working group’s analysis of the FDA MAUDE database demonstrated that the majority of adverse events are related to human factors/user error rather than to technical pump malfunctions. Of course, the lack of standardized adverse event reporting may influence this finding. Additionally, such errors may decrease over time as device interfaces improve with greater company and FDA focus more on human factors.
- The core of the statement is a series of specific recommended actions that could be implemented to address the shortcomings in the regulatory system. The recommendations are divided by those that apply to: (i) regulators; (ii) pump manufacturing companies; (iii) international and national professional societies; (iv) international and national research funding bodies; and (v) healthcare teams. Highlights are described in detail below:
- Regulatory bodies (EU Commission/FDA) should:
- “Harmonize standards to be met by pump manufacturing companies at both pre- and post-marking stages.” In our view, this would represent a terrific win for device companies, as FDA and European requirements differ, in many cases dramatically..
- Provide a single publically accessible international database for adverse event reporting that is better searchable by clinically relevant keywords – demographics, user errors, model/year of pump, consequences of adverse events. The most highly regarded registry in the view of many experts is the Swedish National Diabetes Registry, which contains 95% of all known patients with type 1 diabetes in the country. In February, an FDA blog post shared that “tremendous progress” has been made in developing a medical device post-market surveillance system that “quickly identifies poorly performing devices, accurately characterizes and disseminates risk and benefit information about real-world device performance, and efficiently generates data to help support premarket clearance or approval of new devices and new uses of currently marketed devices.” This is clearly on the FDA’s radar, though the timing and extent to which Europe is involved remain unclear to us.
- Pump manufacturing companies should be required to provide: (i) annual estimates of the number of individuals who use their pumps (what a win this would be!); (ii) the results of clinical research conducted into human factors associated with the design; (iii) updated data on the compatibility of pumps with specific insulin formulations; (iv) data on durability, precision over years of real-world clinical usage; (v) open data on results of testing pumps that are recalled; and (vi) fully anonymized reports of all adverse events.
- Additionally, Dr. Heinemann stressed that the analysis of insulin infusion set adverse events is another critical regulatory question. Of course, this is challenging in practice, since infusion set issues are not always obvious to patients wearing them.
- International and national research funding bodies should provide funding for independent clinical trials of safety, efficacy, outcomes, and adherence and for long-term data collection within new and existing registries. We continue to wonder about the potential to approve products based on smaller studies, with larger, real-world studies in the post-marketing phase.
- International and national professional societies should: (i) recommend appropriate forms of structured education required for new and established pump users; and (ii) set standards for levels of staffing and skills required by healthcare professionals providing support to pump users.
- Regulatory bodies (EU Commission/FDA) should:
- Dr. Heinemann noted that this is the first of many statements that will examine the performance, safety, and clinical outcomes of various technologies – BGM, CGM, and apps. He joked, “Hopefully the next statement will be published more quickly than the first one.”
- Dr. Heinemann emphasized that the group is not necessarily proposing a more complex regulatory system – instead, the ideal solution would adapt the current regulation to fix existing problems. Of course there is a balance between safety/tighter regulation and getting devices to market faster – the balance historically has been towards the latter in Europe.
- We wonder how the publication of this statement will actually affect the broader industry. The recommendations are not binding, and it is tough to say how manufacturers in particular will respond. Much of the utility may be determined by how regulatory bodies react: Will the FDA and EU Commission follow up on the statement? Can the ADA and EASD play a role?
Questions and Answers
Q: Pump manufacturers often look for the cheapest infusion set. How do we change this situation?
A: In a sense, we see a similar situation with blood glucose monitoring in Germany. The issue I see is that outcomes have not been made clear. The manufacturers have not done a good job examining the outcomes of studies in which different types of infusion sets were used. Patients have also not been able to report that infusion set A works for two days longer than infusion set B. That would help. Right now, we don’t know that it doesn’t make sense to use the cheapest infusion set.
Q: Do you think it should be the duty of the manufacturer or an independent agency? Anything from the manufacturer can be claimed to be self-promotional?
A: Dr. Guido Freckmann (Institut für Diabetes Technologie, Ulm, Germany) and I are advocates of an independent institute doing comparisons. Otherwise, people will say, “this study was paid for by this manufacturer.” So yes, I would fully agree. We have a need for such an institution that can independently evaluate the system. You might say, “Another institute! That’s another source of costs and so on.” But if you think about the amount of money we already spend on this technology, the cost for such an institute would be relatively small. We are going to publish a letter to the editor in Diabetes Care soon that deals with patient-related outcomes. We have a situation in Germany where reimbursement for CGM will hopefully happen within this year. That’s a big step forward. IQWiG has looked at over 100 studies of CGM and seen a positive result with respect to A1c, but not patient-related outcomes. Part of the problem is that the field has not agreed on a set of patient-related outcomes – what I mean by this is quality of life, etc. – to be used. This is also to say we should not to repeat this error with the artificial pancreas. We see a number of companies developing this, and we don’t want each group to use a set of measures where you can’t compare the data. But if we do this, as an academic industry, then we can get reimbursement earlier and that’s good for industry and for patients.
Q: The fact is that pumps are not regulated like blood glucose meters. Has anyone ever discussed having ISO standards for pumps like there are for meters?
A: Interesting. The first thing we have to realize is that insulin delivery is done differently for different pumps. It’s not easy to compare pumps. However, for patients, we can compare their experience with pumps. We can understand that with Pump A, there is a risk of under-insulin utilization. There is a need for a clinical point of view and a safety point of view to better understand how the different pumps are performing in the real world.
Q: I was amazed by the ability of FDA to be cooperative recently. However, it seems as though manufacturers were not. Why?
[Comment]: I don’t think it is unusual that the FDA is attempting to be responsive to legitimate questions. That is more a reflection of the FDA of late. I don’t have any insight into the lack of responsiveness of manufacturers. The FDA, though, has come to embrace this process of harmonization. It’s an amazing achievement to put out over 50 statements that support pharmaceutical products. However, on the device side, there’s much more room for cooperation. I think we can all understand that patients will ultimately be served better if we have harmonization of the various aspects involved in manufacturing.
A: To answer the question about manufacturers, I think that one, they are not used to getting these questions, and two, they do not take us seriously. I think it will depend quite a lot on how we go ahead. How will ADA and EASD follow up on this position statement? If we are able to push it through and convince regulatory people, then probably manufacturers might respond more easily.
Q: Can you comment on the education piece a bit more?
A: In the US, you can get a pump via mail. I think this is one of the issues. If you’re not well educated in terms of using this complex technology, then you’re asking for trouble in a certain sense.
Q: You mentioned that you could get pump by mail. But you can also get a car down the road. We don’t want to take cars away from people. Why take pumps away from people?
A: But you need a driver’s license to operate a car. There is no driver’s license for a pump or CGM. There is no absolute system to circumvent these things. I think we need ways to minimize the risk.
Diabetes Care in a Digital Era
Kelly Close (The diaTribe Foundation, San Francisco, CA)
Ms. Kelly Close discussed the future of diabetes care in a digital era, putting the high enthusiasm for its potential into the context of ongoing and future challenges – you can view her slides here. Ms. Close shared that some of the biggest hurdles to overcome are provider adoption, patient adoption, scalable business models, and reimbursement, noting that a lot has to improve to make digital health relevant and meaningful in the medical system. In her view, it’s still the early 1.0 days in digital health (the Palm Pilot era vs. the smartphone era), and there is tremendous upside to change care delivery and meaningfully impact patient outcomes in the future.
- Ms. Close characterized the current multitude of problems in diabetes care as a “perfect storm”: (i) a growing patient population – 592 million people with diabetes projected in 2035 by IDF; (ii) a shortage of providers – 2,245 patients for every one physician specializing in endocrinology/diabetes in the UK, and a discouraging 4,117 patients per endocrinologist in the US; (iii) less time for patient care (some visits are now as short as 11 minutes!); (iv) higher administrative burden (see Dr. Irl Hirsch’s 2015 rant in DT&T); and (v) fewer dollars to spend globally (already 1 in 9 healthcare dollars is spent on diabetes, according to IDF).
- Mobile health and telemedicine solutions provide an opportunity for more efficient healthcare delivery. Ms. Close highlighted the potential of novel technologies, such as Abbott’s FreeStyle Libre, to facilitate better patient monitoring, self-management, and peace of mind. Similarly, she acknowledged the efforts of companies such as Glooko, diasend, and Tidepool to facilitate more seamless uploading of data. Such efforts can reduce the wasted time spent on downloading data, making it easier for providers and patients to drive therapeutic change.
- Ms. Close emphasized the need to gather data automatically and use algorithms to generate actionable recommendations for patients and providers. She shared that the diabetes field is still grappling with at the first step – simply collecting the data. No one (patients nor providers) has the time or desire to sift through data and make sense of it, though her hope is that the future will see better use of software to recognize patterns, make therapy recommendations, and help patients sort through the complexity of diabetes.
- Ms. Close concluded her presentation by summarizing a number of challenges that lie ahead for companies attempting to enable digital healthcare solutions in diabetes:
- Provider adoption: Ms. Close stressed that there are a number of key factors that determine whether a physician will adopt a given technology, such as whether they get paid for engaging with it. In the current fee-for-service model, she noted that telehealth is often not reimbursed well – the reality is that new technology has to appeal to clinics both in terms of clinical efficacy and the financial investment. Similarly, Ms. Close noted that low-cost, scalable technology that makes patients healthier will be key as more and more physicians are on the hook for improving outcomes.
- Patient adoption: Companies have to create digital tools that patients are going to want to use and are going to enjoy using. Said Ms. Close, “the challenge for products is something that is fun, improves health, and fits into life. That’s a tall order.”
- Regulation: Ms. Close stressed that striking the right balance between regulating successfully and interfering with innovation is tough. She acknowledged that the FDA has recently taken a more hands-off approach to digital health by downclassifying the secondary display of CGM data. We would agree that the Agency is moving in the right direction, though there are still gray areas in terms of whether an app treats and manages a disease and will be regulated.
- A scalable business model: Technology needs to be deployable to many people on a population level at a cost that makes sense for everybody – the patient, the company, and the healthcare system.
- Reimbursement: Ms. Close emphasized the need to show improvements in clinical outcomes and tying those outcomes to economic benefits. Indeed, she said, technology will not be paid for just because it is new; it has to meaningfully improve health outcomes. She also pointed out that clinical trials are typically outside the expertise of technology startups, meaning the road ahead could be tough. We are optimistic that the smartest digital health companies will run small pilots to demonstrate clinical and real-world effectiveness.
- Absence of coordination: Ms. Close noted that the diabetes landscape is fragmented right now, with many different entities paddling in different directions and pursuing siloed agendas. Though the competition is pushing innovation forward in a positive direction, it remains to be seen how all the major players in diabetes can work together going forward.
Questions and Answers
Q: How concerned is the patient community with security?
A: I don’t know the answer to that. My impression is that this is a mounting concern. I think the even bigger question is whether the benefits of connecting online are worth whatever risk there is.
[Comment]: In the Netherlands, the general population is more afraid of it. The patients have embraced it.
[Comment]: In terms of the general population, there is a lack of acceptance that someone has diabetes. For example, we are fighting for airplane pilots in Canada. If a pilot gets diabetes, he will hide it because he will lose his job. I guarantee all of you that you have had a pilot with diabetes at some point. There are several who are hiding it because society is not accepting. It’s really bad. We can learn from those who have AIDS. They are coming out, and those patients are now in a much better position than those with diabetes. There is no communication. Your story is great, you are coming out so energetically, but I think about how difficult it is.
Q: I think one of the very key solutions not getting realized is big data. No offense, but when we talk about using data to make decisions, there needs to be methodology and models. We get what we think is information but it is actually misleading. People need to understand the importance of the methodology behind big data. The media doesn’t know what they are talking about. We could go around the methodology, but we should not do that.
A: That’s an interesting point. What area do you think diabetes can learn from in this sense?
[Comment]: Mr. Tim Hartford has written a great piece about that in the Financial Times.[Editor’s Note: This is indeed an outstanding article on some of the statistical dangers of “Big Data.”] The message isn’t that our data is all wrong, but we need to acknowledge the importance of good information. This was written in March of last year. In ten minutes, you will learn more about big data than you know today.
Q: One thing that you pointed out is the need to prove efficacy. The number of apps is growing fast and is a bit out of control. How can we build up programs that evaluate the efficacy and safety of these applications?
A: This is such a good question. The digital age is bringing about a lot of questions on this front, and there is a need for resources. This is why the diaTribe Foundation wants to bring in smart people to help with this. When I was diagnosed, there were 30 million people globally with diabetes. Now there are 30 million in the US alone. I don’t know if the best place is to look to government to fund this, but we are going through a period of unprecedented wealth creation on the technology front and that adds to the potential. I’m thinking here about Apple and Google who are saying they don’t know everything in the diabetes space, so it’s up to us to help them. Honestly, I think they would understand this problem much better than some of us in the diabetes community.
Dr. Robert Ratner: One question I have is how do you vet the information that is online for safety?
A: I don’t have a good answer for that either. I think that one thing that has worked to some extent is the sheer numbers. Some people say really disparaging things online. I think it makes it really important for us as a community to look and see how we can expand the resources coming in to be able to address some of this. We must harness the media in a much better way, because the way we are doing it now is not good.
Experiences from Other Associations
Medical Devices in the USA 2015
Robert Ratner, MD (Chief Scientific and Medical Officer, ADA, Alexandria, VA)
Dr. Robert Ratner provided a strikingly positive appraisal of the FDA’s recent efforts on the diabetes device regulatory front. Indeed, he opened his lecture with a bit of levity – “Much like everyone in America, the FDA has a bit of overblown image of themselves … but for the last six months, they have been working hard and doing good work.” Dr. Ratner cited two instances of the FDA’s success in particular: (i) its Public Workshop on medical device and healthcare cybersecurity in October 2014; and (ii) its Public Workshop on diabetes device interoperability and bolus calculators in November 2014. Not only has the Agency shown an increasingly patient-oriented spirit, he said, but regulators have shown a willingness to act decisively and promptly. In particular, he highlighted the FDA’s January downclassification of the secondary display of CGM data (with the approval of Dexcom’s Share Receiver) as an example of the growing appreciation to foster innovation that meaningfully impacts patients and keeps up with technology. On interoperability, Dr. Ratner provided a stirring call to action, noting that both the US and EU are far behind where they could be in terms establishing standards for data formatting, integration, and downloading – “The reality is that if you don’t have access to data, you have no choice and it serves no purpose.” It was stirring commentary backed up by findings from the T1D Exchange (a group that we typically think of as representing the most engaged type 1 patients) illustrating that > 50% of pump/BGM/CGM users NEVER upload their data (see below).
- Dr. Ratner was critical of the current state of interoperability, noting that it is a no-brainer to simplify access to data. He highlighted that patients with diabetes are self-administering one of the world’s most dangerous drugs every single day and that the complexity associated with accessing blood glucose information (“millions” of different cables, inconsistent data formats, etc.) is simply “silly.” We would wholeheartedly agree that inconvenient data downloading represents an important hurdle to patient self-management and helping providers drive therapeutic change. In recent months, it has been encouraging to see progress from Dexcom, Diasend, Glooko, and Tidepool on this front. Still, making the downloading easy is only the first step, especially because few providers have time to look at it and few patients want to spend more time on diabetes. What’s just as critical as building systems that can automatically analyze the data and recommend changes.
- Dr. Ratner shared data from the T1D Exchange – a group that we typically think of as representing the most engaged type 1 patients – to illustrate just how challenging data downloading is for even the most motivated patients. More than 50% of pump/BGM/CGM users never upload their data, and less than 10% upload their data more than once per week. We think this speaks to both the challenges of uploading data right now, as well as how boring and confusing it is to interpret it. Many patients may be doing a cost-benefit analysis on whether to upload their data and look at it – right now, the time/hassle costs are too high, and the benefits are usually non-existent (hard to interpret and piece together what should be changed).
Table 2: Challenges of Data Downloading (from the T1D Exchange)
Participants who upload their data more than once per week
Participants who NEVER upload their data
- Dr. Ratner described stakeholder cooperation as one of the biggest hurdles to interoperability. A key question in our mind is whether industry can come together to standardize data formats and/or achieve greater device integration. We are hopeful that FDA involvement will be able to align incentives, and as Dr. Ratner pointed out, there is a precedent on this front in computer software (e.g., set formats for JPEGs, set formats for PDFs). As a reminder, the JDRF and the University Health Network in Toronto recently published an IEEE standard for CGM communication and interoperability. Other standards are in development for pumps and BGMs. It remains to be seen whether manufacturers will incorporate the voluntary standards, though Dr. Ratner suggested that the field is on a promising trajectory.
Questions and Answers
Q: What is the current state of harmonization? Are we at the beginning of the effort? Can on talk about the workshop on interoperability?
A: The workshop occurred in November 2014. The consolidation is very new. The idea is finding the interface and platform that everything can go through for common interaction. That’s really the intent. The FDA has contracted with two companies that I’m aware of. But perhaps our industry partners can tell us more about how far along this really is.
Q: What is your opinion about the ability of healthcare professionals to assist the patient? We have ivory towers because their knowledge is not great about these systems. Do you think that the education of doctors and nurses is important?
A: When primary care providers are seeing 60 patients per day, it’s hard to expect them to do extra work on the patient with diabetes. What I’ve learned in my career as a teacher is that the best way to get people to adopt something is to get them to understand how it is going to make their lives easier. Right now, devices don’t make physicians lives easier. It makes them harder. However, if we have interoperability, then we can teach healthcare professionals to interpret data within that presentation, and it will make lives easier. Until we do that, this will not be adopted.
Q: Interoperability is important. The FDA is trying to get companies to work together. But do you really think companies will do that? In the real world, how do you think about this? Can we realistically expect industry to come together?
A: Take a look at your computer and look at set formats for JPEGs and set formats for PDFs. It’s been done. It’s been done with DVDs. It’s been done – less successfully – with old Beta Max and VHS. Industry can come together, and everybody does ultimately benefit.
[Comment]: I think it’s an external factor that has to drive this. If you ask industry to come up with it themselves, that’s significant challenge.
A: That’s what the FDA is trying to do. I think, if left to their own devices, industry says “our system is the best and everyone will come to us.”
Q: The other thing is, “Welcome to the EU.” Sometimes we wish that the EU Commission would lead more and impose more and provide some kind of standards. We have 28 countries. We might be even more tomorrow. Every time, it’s an extra challenge.
A: I don’t know if you have looked at a US newspaper recently. We have 50 states and they are almost as contentious as the EU is.
The ERS (European Respiratory Society) Experience
Brendan Cooper, PhD (University Hospital Birmingham, UK)
Speaking from his experience with the European Respiratory Society, Dr. Brendan Cooper discussed the importance of balancing safety and innovation when developing standards for medical devices. He noted hearing much on the safety side during the day’s discussion, though reminded attendees that stricter standards may stifle innovation. In his eyes, the fact that the CE Marking process “tends to be ~3-5 years ahead of the FDA” is not something to be taken lightly. Building on the topic of standards, he stressed that the establishment of the ERS’s current standards for medical devices involved a “very complex process with many people involved” and that he sees parallels in the complexity of the diabetes ecosystem. Speaking more broadly, Dr. Cooper wondered aloud whether a “Euro FDA” might help address this complexity by providing a centralized agency to push such standards forward – “Do we want that? Can we afford that?” He ultimately concluded that such an agency was not practical in the EU given the diversity of Members State and budget limitations. Given the lack of such a body, he emphasized that achieving harmonization between the many stakeholders in the diabetes space will be key for the field moving forward.
- In Dr. Cooper’s view, the growing ecosystem of medical mobile apps is an area that needs increasing regulatory scrutiny in the very near future. He noted that the FDA has already taken positive steps on this front with its guidance on Mobile Medical Applications, though the effort is not sufficient in his view. Dr. Cooper believes that apps are slipping through the cracks, allowing patients to get their hands on platforms that could ultimately be harmful. He noted that the EU is further behind on this front and needs to duplicate such a document “very soon.”
Questions and Answers
Dr. John Brennan (MedTech Europe, Brussels, Belgium): One of the problems we’re facing right now in diabetes is that the EU Commission is blocking all efforts at achieving harmonized standards. Can you comment on when you did all of this work? How disappointed would you be if that got bureaucratically blocked [as it is with efforts in diabetes]?
A: Well that would be the worst, wouldn’t it?
[Comment] Dr. Eric Hanssen (EU Commission, Brussels, Belgium): From our perspective, we are trying to make sure that the standards are correct. We are trying to solve these issues. I think there is a fundamental problem with standardization in this field, because it’s drawn up by industry across the world and not suited to EU needs. We need to get more European regulators involved in this work.
The Bionic Pancreas – A Dawn of Hope
The Bionic Pancreas – When Will the Dream Come True?
Steve Russell, MD, PhD (Massachusetts General Hospital, Boston, MA)
Dr. Steve Russell’s (MGH, Boston, MA) comprehensive overview of the Bionic Pancreas shared an updated timeline on commercialization – now “2018,” a bit back of the longstanding goal to bring it to market by 2017 (when Dr. Ed Damiano’s son with type 1 diabetes enters college). The slight deferral is not surprising considering how ambitious the timeline has been to date – indeed, we’ve been truly impressed with the ability to stay on a schedule originally laid out in 2012! The team hopes to conduct its pivotal study in 2016-2017. Based on Dr. Russell’s remarks, it sounds like the approval of glucagon has pushed the commercialization back a bit, along with the new NIH funding opportunity for the pivotal study. In very positive news, Dr. Russell presented the latest interim results from the ongoing Bionic Pancreas 11-day multicenter study (thirteen additional patients from the seven presented at DTM 2014 in November). The team is now three-quarters done with the trial as Dr. Russell confirmed that the Stanford study has wrapped up (though data was not yet available to be shared). The UNC Chapel Hill arm (the final 10 patients of 40) began in March.
- Looking ahead, the team hopes to conduct its pivotal study in 2016-2017, with FDA premarket approval slated for 2017-2018 and commercial launch in 2018.The Bionic Pancreas pre-pivotal glycemic set-point study is now being considered for 2015-2016, which Dr. Damiano had previously hoped would take place in 1H15. As of the last update, an alcohol tolerance clamp was slated to begin in 4Q14 – we are unclear whether this has begun. An additional pediatric study was also being considered for 2015 that we assume is still on-track to begin this summer.
- In a follow-up conversation, Dr. Damiano attributed much of the slippage in the timeline to a positive development: the receipt of the NIH DP3 Grant that funded the team’s multi-center study. As background, Dr. Damiano reminded us that the multi-center study was originally envisioned as a single center “Hospital Staff Study” taking place in the first half of 2014 (at Massachusetts General Hospital). However, upon receiving the grant, the team chose to add nine months to the study to integrate three additional sites (UMass, Stanford, and UNC; allowing three months for each site). That delay did push back the original timeline, and it did not help that the team’s funding for device development work ran dry for three months last spring. That said, Dr. Damiano stressed that the UNC site is still scheduled to finish by mid-April, consistent with the timeline the team proposed in their NIH grant.
- For the pivotal study, Dr. Russell confirmed that the team is seeking funding via the NIDDK’s recently announced initiative, entitled: “Advanced Clinical Trials to Test Artificial Pancreas Device Systems in Type 1 Diabetes.” The criteria for proposed trials are fairly general, and Dr. Russell noted that the team is still figuring out what the study will look like. Applications are due by April 15, 2015, with the earliest start date slated for December 2015.
Table 1: Roadmap to a Bionic Pancreas
Beacon Hill Study
Summer Camp Studies
Review of Premarket Approval Application by FDA
* bold = not yet initiated
- Dr. Russell noted that the biggest hurdle to commercialization remains the development and FDA approval of a stable glucagon formulation. At this point, we imagine that an approval for chronic use of a glucagon is the thorniest regulatory issue for the team to wrestle with. On the development front, Dr. Russell shared positive news highlighting topline results of Xeris’ glucagon published in January (Newswanger et al., JDST 2015). The study was conducted in pigs and demonstrated that there is no difference in pharmacokinetic or pharmacodynamics profile between Xeris’ fresh formulation and Novo Nordisk’s glucagon. Dr. Russell noted that there is similar data in humans, though it has yet to been fully analyzed.
- Dr. Russell presented a slide with the latest interim results from the multicenter study. Average glucose has been 139 mg/dl (an approximate A1c of ~6.5%) in those on the Bionic Pancreas, with just 0.7% of the time spent in hypoglycemia (<60 mg/dl). The time in hypoglycemia continues to show a notable improvement over that of prior outpatient Bionic Pancreas studies (which consistently exceeded 1%). In the usual care arm, average glucose has been 163 mg/dl, with more than double the time (1.6%) spent <60 mg/dl. Notably, these are motivated patients in superb control to begin with, and we are impressed to see that the Bionic Pancreas is able to bring them safely into even tighter control.
- Dr. Russell emphasized that the Bionic Pancreas (BP) has not delivered more insulin than usual care (UC) [0.69 units/kg/day UC vs. 0.70 units/kg/day BP] nor has there been excessive glucagon usage (~450 ug/day BP). This is notable in light of recent criticisms that the Bionic Pancreas’ use of insulin and glucagon is “aggressive.” At DTM 2014, Dr. Roman Hovorka highlighted that in the Beacon Hill study, participants had a 32% increase in their daily insulin dose during closed-loop. He implied that the increase results from a “stop-and-go” approach to hormone administration that, in his eyes, aggressively doses insulin and depends on glucagon to counteract that “excessive” administration. So far, it appears that the multicenter trial has differed from the data gathered in Beacon Hill, and perhaps these criticisms will be less of a concern going forward.
- Dr. Russell again shared topline results from the 2014 Summer Camp study in pre-adolescents (first shown in October at CMHC 2014), which were very consistent with prior and ongoing results: participants in the bionic pancreas group had an average blood glucose of 137 mg/dl (estimated mean A1c of ~6.4%, with all participants under the ADA goal of 7.5% for teens and pre-teens) and spent significantly less time < 60 mg/dl (1.2%) and > 180 mg/dl (17%) compared to the control condition.
The Artificial Beta cell: European Research
Lalantha Leelarathna, MD (Central Manchester University Hospital, UK)
Dr. Lalantha Leelarathna provided a comprehensive overview of European efforts in the closed-loop field, especially in the home environment with the Cambridge and DREAM groups. He did not share new data, but highlighted the impressive results of his group’s three recent at-home studies (APCam06; Angela03; AP@Home02) while calling out the “truly impressive” data from the DREAM consortium’s 24-patient, six-week, at-home, crossover trial. Dr. Leelarathna suggested that the DREAM group is setting the bar for closed-loop work, but also touched on the progress of bihormonal research in Amsterdam and shared very strong data from the latest overnight studies of UVA’s DiAs in Europe.
- Dr. Leelarathna highlighted the bihormonal closed-loop research taking place under Drs. Adrianne van Bon and Hans De Vries (Academic Medical Center, Amsterdam, Netherlands). The group recently conducted a single-center trial examining the feasibility of a fully closed-loop system (no meal or exercise announcements) used for 48 hours at home. (Data was first presented at ATTD 2014.) The study (n=11) ran into technical difficulties, but demonstrated a tendency toward improved time-in-range (open loop [OL] ~67% vs. closed loop [CL] 78%). Lower median glucose levels were seen on Day 2 (~159 mg/dl OL vs. ~139 mmol/L CL), though time spent in hypoglycemia also went up during closed-loop (2.8%) vs. open loop (0%). We would point out that the device also used a significant amount of glucagon (~2.2 mg/day vs. ~0.8 mg/day physiological exposure). Ultimately, the work seems very early stage relative to the Bionic Pancreas team, but we will stay tuned for more.
- In the outpatient setting, Dr. Leelarathna shared the latest data from overnight studies of UVA’s DiAs system in three centers across Amsterdam and Italy. Average time spent in hypoglycemia was 1.4% for patients on DiAs vs. 10.6% for patients on pump therapy alone (p-value < 0.01) – that must be one of the largest deltas we’ve ever seen. There was also an improvement in time-in-target, 84% (DiAs) vs. 62% (pump) (p-value = 0.04), which was seen both during the overnight and daytime periods. As a reminder, the UVA group has moved into home trials, and we await data from the multicenter 2-month study conducted in 2014.
Medical Devices in Europe – Emerging Political Issues
The Strengthening of the EU Medical Devices Regulatory System
Erik Hansson (Deputy Head of Unit, European Commission, Brussels, Belgium)
Mr. Erik Hansson provided a valuable appraisal of the state of play in EU negotiations to tighten the medical device regulatory approval process. The proposed legislative changes would increase scrutiny of devices submitted for CE Marking, but they are still under debate at the EU member states level. Our understanding is that most of the proposed changes are for high risk class III devices (e.g., heart valves) while diabetes devices are class IIb and IIa. Still, Mr. Hansson provided a striking reminder of how slowly progress is moving as he pointed out that reform efforts began in 2008. We learned that the earliest the legislative changes could be signed into law is late 2015 (though early 2016 sounds more likely), which means the law likely wouldn’t take full effect until ~2018-2019. Despite the slow speed of progress, Mr. Hansson did note that some controls on medical devices have already been strengthened. We learned that some Notified Bodies have already been “downclassified” through both voluntary and mandatory joint audits – our understanding is that this means their regulatory license has been revoked. Mr. Hansson stressed that these are steps in right direction.
- Looking to the future, Mr. Hansson expressed hope that “we will see more specializing of Notified Bodies.” One of the biggest concerns with the current system is that there are no Notified Bodies with specific background in diabetes devices. On the one hand, the organization makes notified bodies flexible and speedy in terms of regulatory approval, since innovative technologies can be submitted to any Notified Body. However, the significant tradeoff is that no agency has the competency to comprehensively vet a diabetes device. We hope that the EU finds a middle ground, as we could imagine that having only a few Notified Bodies specializing in diabetes could have a significantly negative impact by slowing the speed of regulation.
- Mr. Hansson acknowledged that a centralized European agency (e.g., an EMA for devices) would offer a compelling a solution to the presently fragmented ecosystem – “[Do we need a principal agency?] The answer is definitely yes. But on a political level, the answer is a no.” Funding is the critical hurdle to be overcome, and it sounds like resistance in the EU Parliament and Council is so stiff as to make the likelihood of this happening “next to impossible.” We certainly realize that the EU economic climate has resulted in slim budgets. Coupled with declining industry margins in some areas (e.g., BGM), it’s hard to say how this will be resolved. Indeed, we were surprised that the impact of funding constraints on regulatory review did not come up more often in the day’s discussion.
Questions and Answers
Dr. Andrew Boulton: The EASD really feels that for invasive devices – where there is a life-threatening consequence for a failure – there is a need for a centrally run European devices agency. Sure, there are fiscal challenges, but shouldn’t we work toward that for class II and III devices? How would you answer that?
A: The answer is definitely yes. But on a political level, the answer is a no. Just to make clear, on the EU Commission, we are 12 persons. This is not a very big force to work with this. We are trying to get help from the Joint Resource Center, but their expertise is with resources, not regulation. What we have seen is that whenever the issue of a new agency is raised, the idea is shot down immediately because this just cannot be done in the context of the financial crisis. We are losing people in the medical devices unit and to get the resources to expand is almost impossible. So definitely, there is a need for this. We would be very pleased if that would happen. But politically, it is going to be very difficult to make this happen.
Q: The EMA has changed its “risk-benefit” analyses into “benefit-risk” analyses. You have talked about scandals. I would just say that there is a need to stop the discussion about risks and scandals and focus on the benefits.
A: You’re right. I think that here the benefits are obvious, so we don’t need to necessarily mention them. I’d be delighted not to mention the scandals. However, the scandals have caused many of the difficulties we have. If it were not for the PIP breast implant scandal, we would have had the new legislation already and wouldn’t have as much interest from Parliament and wouldn’t have to deal with brilliant – and less brilliant proposals – and so on. That’s why unfortunately the scandals are important.
Q: Could you explain Eudamed?
A: It’s a database where devices are registered. In the future, this will list more information on the characteristics of devices and adverse events associated with them. However, right now, the database is not fully functional because not all the data is entered. However, we want to ensure that this is fixed in the future. Also, we believe that a big part of the data should be made public.
Q: Could you speak more about the Notified Body closures that you mentioned during your talk? What problems did you find?
A: The main problems actually had to do with the clinical aspects. Some Notified Bodies were not sufficiently looking into the clinical data. This is a major problem. Another issue is that several of the Notified Bodies are also active under other sectors of industry, such as electrical products. What this means is that they have good general knowledge, but not specialized knowledge. This is something that they have needed to improve and do a better job with. Another reason some have stopped their activities is that they haven’t had the money to improve on these issues. We will probably see more specializing of Notified Bodies in the future.
Q: Where were these Notified Bodies closed? What were the specific locations? And have you approved any new ones?
A: There have been some applications for new ones, but none have been approved so far. In terms of those that have closed down, I would encourage you to check our database.
Birgit Berger (Secretary General, Standing Committee of European Doctors, Brussels, Belgium)
Ms. Birgit Berger provided an urgent call to action on the cybersecurity front. She emphasized that while wirelessly controlled medical device have become more widespread, the risks associated with confidentiality and integrity of data have grown exponentially. She contrasted these risks with the inadequate status of cybersecurity regulation in the EU – “This is not fit for practice anymore. It’s stuck in the 20th century and needs to move forward.” On a positive note, she pointed out that the EU Council is working on an initiative on this front that would tighten regulatory standards for connected medical technologies. The initiative was not described in detail though we hope to hear more on this in the future – however, given the pace of the EU regulatory process, our sense is that changes should not be expected in the near term. Ms. Berger concluded by reminding us that ensuring secure medical devices is essential for high-quality medicine, but that these concerns should not take the place of innovation. Indeed, calls for balance were a theme on the day, though it’s of course easier said than done – and the conversation shifted much more towards promoting greater safety and tightening up the process in Europe.
The New MDD/IVD regulations
John Brennan (Director of Regulations and Industry Policy, MedTech Europe, Brussels, Belgium)
Mr. John Brennan of MedTech Europe (a medical device trade association that represents manufacturers) opened his presentation by reflecting on the slow speed of EU regulatory efforts and delivering a message of frustration – “This is the third year I’ve spoken at this conference, and this is the third time that I’m going to say exactly the same thing.” He stressed that there needs to be a greater level of urgency, as the lengthy state of current negotiations is actually hurting patients by keeping positive changes from being implemented. Mr. Brennan suggested that regulators have lost sight of these benefits and are holding the reforms to too high a standard. Notably, he acknowledged that the current legislation is not perfect, but emphasized that it does not need to be, especially given the woefully inadequate existing regulatory structure. As he concluded: “We have good ideas on the table, and I think we should move forward with that.”
- While “much has already improved in the EU,” Mr. Brennan discussed a number of further improvements he would like to see moving forward. This discussion was highlighted by the need for a more standardized and transparent system of collecting adverse event data. Mr. Brennan stressed that there is little data on medical device performance in the EU and even less that is available to the public. As a reminder, the EU does have a database where devices are registered – Eudamed – though our understanding is that the resource is not fully functional because of significant gaps in data entry. We would imagine that funding and mandating such efforts represent hurdles, as well as achieving industry consensus on what measures to report and how to do so.
- Mr. Brennan noted that the ideal regulatory system might lie somewhere in between the current structures in the US and EU. He noted ironically that while the FDA is currently engaged in discussions to speed up its regulatory process, the EU is attempting to become more deliberate. He suggested that both agencies see the benefits and risks of the alternative structure and are modifying their approaches to reflect these learnings. At the end of the day, he stressed that industry wants a clear, predictable, and effective system – it does not have to be perfect, but it has to work.
Questions and Answers
Q: I like the idea to monitor Notified Bodies more strictly. However, with devices we use like pumps and CGM, shouldn’t we be setting up proper Notified Bodies with experience in diabetes?
A: I fully agree. I think one of the advantages in the EU is that we have a classification that 99% of the time delivers the product into the right risk category. Now, the next step is figuring out Notified Bodies, though I think there is also the importance of establishing standards so that Notified Bodies and manufacturers are consistently producing a high quality product.
The Role of MedTech Europe – A View Beyond Regulations
Serge Bernasconi (CEO, MedTech Europe, Brussels, Belgium)
Mr. Serge Bernasconi opened his presentation with the day’s most emotionally charged plea to accelerate the pace of legislative efforts (see below for a transcript of his opening speech). Mr. Bernasconi reprised the need to focus on the potential of current reform measures rather than deliberating over whether the reform will be perfect. Indeed, he was somewhat critical of policymakers, who he believes have been paralyzed by the notion of prioritizing patient safety and who are dissatisfied with what is already an adequate solution. He implied that policymakers want to eliminate the risks associated with medical device use entirely, an ambitious and laudable goal, though one that overlooks the fact that people with diabetes live with risk every day. As a solution, he suggested that more dialogue is needed between all the relevant players in this field – governments, professional societies and patients – and, to that end, announced that MedTech Europe has created a new agency – the “Sector Group for Diabetes” – to generate such dialogue. The agency’s objectives are to raise diabetes on the agenda of the EU policymakers and to encourage movement toward more patient-centered diabetes thinking. We do not fully know what power the agency holds, though are certainly encouraged to see MedTech Europe prioritizing the field of diabetes.
- Mr. Bernasconi focused on the challenges of getting the diabetes field to utilize available technology to its full extent. He suggested that technological innovation will not mark the next step forward in the field – instead, he believes that the biggest gains in patients outcomes will occur when healthcare providers and patients come to utilize what is already available (e.g., increasing penetration of CGM and pumps, using software to recognize patterns and make therapy recommendations, improving interoperability). He acknowledged that “this will take time” and that “mentalities and structures are not yet ready,” suggesting that the role of MedTech is to help stakeholders appreciate the value proposition of new technology. We believe a key step in driving adoption is making technology much more affordable, particularly in Europe.
- On the regulatory front more broadly, Mr. Bernasconi noted that replicating the real-world environment is an underappreciated challenge of designing pre-market studies. He believes that current study designs are inadequate and tend to extensively support patients in ways that are not seen in practice: “We put 10-20 technicians around a patient and it’s not even their hand anymore.” He stressed that when accuracy and efficacy is examined in the post-market setting, the pre-market data is not duplicated. Mr. Bernasconi concluded that more thorough post-market surveillance is not only critical, but necessary if we are to ensure the safety of devices.
- Dr. Bernasconi opened his lecture with a passionate speech that expressed both a great deal of frustration and hope for the future of the medical device industry. We have included the transcript below:
“I have heard lots about scandals and problems with medical device regulation. I have heard many people ask: “What the hell is this? What kind of an environment is this?” What I would remind you is that there are 500,00 devices in use every day. We don’t hear about 500,000 problems every day … I’m not saying that this is a perfect industry. We have our share of challenges and we have our share of black sheeps. But this industry is based on a vision to change the lives of people and their future.
There is a chance that as you escalate innovation, you escalate risk. However, I actually believe that the opposite is true. If you look at how medicine was practiced 20 years ago and how it is practiced today, we save many more lives than we create problems. I think we need to change the way we look at medical devices. We need to think about them as an opportunity for the future. Let me tell you – we haven’t seen one-tenth of the devices and technology that are still to come. It’s amazing and very exciting … When you see the black sheeps in the industry, the common factor is that they don’t really care about the patients. And that’s when the problems start to develop because they care about the money more than the patient.
However, I want us to understand that the future is bright. The future is good. Yes, there are challenges, but the future is good. I’m sick and tired of hearing about the PIP [Poly Implant Prothèse breast implant] scandal. I’m sick and tired of hearing about metal-on-metal [hip] issues. Why don’t we talk about something else for a change? Let’s talk about how we can transform the future.”
Questions and Answers
Q: Can you talk about the cost-effectiveness of using technology to its full extent?
A: It’s a question that’s not only specific to our industry. Any forward-looking industry faces a big question of how to get patients to accept technology. Innovation with medical devices is troubling for people because we are forcing significant changes in the way medicine is practiced and the way hospitals are managed. This will take time. There’s no way around it. I do think we need to seriously quantify what technology means in terms of savings. If you just bring out the technology, that’s not the solution. If today, all the technology that is out there were used to its full extent, the cost of healthcare would be reduced a very significant amount. Unfortunately, the mentalities and structures are not yet ready. We have to play a bit of a different role because we have to help people realize how they can use technology.
Reimbursement for Medical Devices in Europe
What Makes a Diabetes Device Worth Spending NHS Monies? Experience From the UK
Amanda Adler, PhD, MD (NICE, UK)
Dr. Amanda Adler (NICE, UK) informed attendees that NICE’s assessment of sensor-augmented pump therapy is slated to begin in one month, and a final decision on the Medtronic Veo and Animas Vibe are expected later this spring. This reimbursement decision may have important implications for the future of the artificial pancreas in the UK and we will be waiting eagerly for updates. As she has in the past, Dr. Adler prefaced her overview of NICE’s medical device regulatory review process by putting the challenging English reimbursement landscape in blunt perspective, emphasizing that the agency’s objective is to identify therapies that maximize economic utility. On this front, Dr. Alder noted that she was sharing her personal perspective that did not necessarily reflect the views of NICE.
- Dr. Adler prefaced her talk by putting the challenging English reimbursement landscape in blunt perspective – “Money is limited. And with limited funds and many choices, one has to make very difficult decisions.” We thought she struck a conciliatory tone, emphasizing the challenge of maximizing clinical utility for patients across all disease states, not just those with diabetes. We certainly appreciate that this process is complex, and judging from Dr. Alder’s description, conducting cross-disease state comparisons (for example, a cost-benefit analysis of myocardial infarctions vs. severe hypoglycemia) is not an enviable one. That said, from a patient perspective, it is quite disappointing to hear that cost-utility is such a paramount consideration for NICE – especially when softer efficacy wins, such as reduced mental burden, are tough to value.
- Dr. Adler highlighted that A1c is a primary component of NICE’s process, which is used to model quality-adjusted life years and the cost of complications/adverse outcomes. However, she spoke about the quantification in vague terms, “Imagine that a device does reduce A1c. Then we might imagine that NICE might roll that through and assume a reduced chance of death.” She seemed to acknowledge that the process is not perfect, a fact that is concerning for us, particularly as next-gen therapies come to market that may reduce hypoglycemia and/or hyperglycemia, but might not impact A1c. We do believe such technologies could show a benefit on severe hypoglycemia with a much less onerous outcomes study than something like the DCCT.
- Speaking of next-gen technologies, Dr. Adler informed us that NICE’s assessment of sensor-augmented pump (SAP) therapy is slated to begin in one month. As a reminder, two SAPs – the Animas Vibe insulin pump integrated with Dexcom’s G4 Platinum CGM and Medtronic Veo – are currently CE Marked. The devices have seen positive penetration in other EU markets, and NICE reimbursement would go a long way toward bringing this technology to patients in Britain. Of course, the reimbursement decision also has potential implications for the future of artificial pancreas reimbursement in the region and will be waiting eagerly for updates. A final decision is expected later this spring.
Questions and Answers
Q: In your discussions at NICE, do you talk about how technology can allow people to work better and longer? That influences quality of life.
A: You ask a very good question. We are tasked with looking at diabetes and cancer and Alzheimer’s all at the same time, so we don’t take into account indirect benefits like going to work. But in our discussions, we do talk about that sort of thing. And we do talk about that in quality of life.
Reimbursement for Medical Devices in France through HAS and ANSM
Jacques Belghiti, MD (HAS, France)
Dr. Jacques Belghiti provided an overview of the French reimbursement process that is orchestrated by the National Authority for Health (HAS). Dr. Belghiti emphasized that the HAS strives for balance in its reimbursement decisions, weighing both the efficacy of therapy and cost utility. Indeed, the primary way in which he distinguished between the goals of the HAS and NHS was in his belief that his agency is far less cost-centered compared to its English counterpart (see above). While he expressed confidence in the French pre-market review process, he suggested that the inadequacy of post-market studies remains an area for improvement for France – “I must confess that this is the major challenge and the thing we have to change in the future.” We appreciated this perspective and felt that though Dr. Belghiti struck an optimistic tone, his message was that the need for such changes are not currently in the HAS spotlight. The agency’s current focus is actually on establishing a provision for conditional reimbursement of innovative medical devices – our understanding is that this could apply to closed-loop technologies. The goal of the new measure is to accelerate the speed with which breakthrough technologies reach patient hands; though this was not discussed in detail, we believe the measure grants a committee the right to provisionally reimburse a CE Marked device while ongoing studies establish the benefit of the procedure.
- The HAS asked two primary questions in its review process: (i) Should the medical device be reimbursed based on literature, expert opinion, and public health impact? and (ii) Does the medical device in question improve patients’ clinical situation as compared to existing therapies?
- A slide titled, “Innovation for Innovation,” highlighted a recent HAS initiative to create a provisional reimbursement scheme for technologies that have the potential to “rupture” the market. The criteria for such a device include that: (i) it is already CE Marked; (ii) there is no official financial support; (iii) there is an argument in favor of beneficial clinical or economic improvement; (iv) there is no argument for specific risks; and (v) there is insufficient data for a regular assessment. The initiative establishes a committee that will decide (in one month) whether a technology is “innovative” enough to deserve provisional reimbursement. This will allow the technology to be financial supported for 3-5 years, while an ongoing study assesses the clinical benefit.
- We are excited to hear of this initiative, especially as we think that the measure has implications for the reimbursement of closed-loop technologies. Automated insulin delivery systems is likely to represent a big breakthrough for patients once hybrid closed loop and fully automated systems are approved. Technology is meaningless if it does not reach patients, and it is great to see the HAS thinking ahead of the curve. We hope the move has positive implications for diabetes devices.
Guillaume Charpentier, MD (Sud-Francilien Hospital, France)
Dr. Guillaume Charpentier provided a clinician’s perspective on France’s healthcare system. He acknowledged that the country has taken positive steps on the reimbursement front – e.g., 100% pump reimbursement by social security in patients whose diabetes cannot be controlled via MDI (established in 2000) – though a number of obstacles remain to optimize the use of such complex devices in the population. In particular, he highlighted an inadequate education system that leaves both providers and patients unequipped to utilize a pump. This problem is exacerbated by the shortage of providers who can provide follow-up care, resulting in many patients who do not fully understand how to take insulin. His words were a stirring reminder that diabetes is overwhelmingly a self-managed disease and that without patient investment, even the best technologies become underutilized.
- Dr. Charpentier highlighted telemedicine as a solution to the shortage of endocrine specialists in France, though noted that reimbursement of remote technologies is a huge hurdle – “It is difficult to reimburse this. Very difficult.” However, we did learn of one telemedicine app (the “Diabeo” system) that is available to type 1 patients in France. The app consists of a self-adjusting insulin calculator, and more notably, facilitates follow-up telemonitoring appointments with nurses under the supervision of a diabetes specialist.
- Dr. Charpentier re-emphasized the need for improved post-market surveillance in France. Indeed, he estimated that 25% of pumps in France are returned to manufacturers each year, though only a fraction of these are reported to the regulatory agency. One out of four pumps sounds incredibly high to us, and we wonder what that estimate is based on. In many ways, the post-market surveillance systems seems to be plagued by many of the same issues apparent in the US (lack of standardized report, funding constraints, etc.).
Reimbursement of Continuous Glucose Monitoring (CGM) in Germany
Stefan Sauerland (IQWiG, Germany)
A bold statement highlighted Dr. Stefan Sauerland’s (IQWiG, Germany) summary of the general principles of reimbursement at Germany’s Institute for Quality and Efficiency in Health Care (IQWiG) – “We do not look at costs … We only look at effectiveness.” It was one of the more patient-centered attitudes we heard from a reimbursement agency on the day, though the statement was met with much skepticism from attendees. As a reminder, IQWiG has been particularly challenging in diabetes. On the drug front, the agency found no added benefit with Sanofi’s Lyxumia (lixisenatide) in 2013 (prompting the drug’s withdrawal) and in 2007 ruled that the benefit of then-Lilly’s Byetta (exenatide) was not yet proven. On the device side, the decision on CGM reimbursement continues to proceed slowly (it started in 2011!), though Dr. Sauerland suggested that a decision is expected in “2015 or 2016.” Ultimately, we find that is tough to get a grasp on how IQWiG is thinking about diabetes. The reimbursement process is complex, obscured by bureaucratic red tape and semantics (such as today’s patient-oriented spirit), and we hope to see actionable changes in the future.
- Said Dr. Sauerland, “We have problems with A1c. We try to look at mortality, morbidity, and QALY data in our assessment. We want to see that the patient has an advantage.” While we applaud this patient-oriented spirit, we would emphasize that there is a lot of nuance surrounding the discussion of A1c. Certainly, A1c has its downsides as a 2-3 month average that fails to capture hypoglycemia and hyperglycemia. However, IQWiG’s decision to deprioritize the measure is confusing, since long-term mortality/morbidity data is simply not feasible in this constrained financial environment (not to mention the effect such long-term studies would have on stifling innovation). We’re not sure where that leaves things.
- Dr. Sauerland provided a valuable overview of the status of CGM reimbursement, expressing cautious optimism that a decision from IQWiG will come in the next two years. It has been a long process to date – complicated by legal issues – though the committee is in the process of finalizing the final report. This report will be sent to Germany’s Federal Joint Committee in March 2015, such that a final decision is “expected by 2015 or 2016.” Though this is a wide-open timeline, we are glad to see some progress on this front. See below for an overview of the overall timeline.
Table 3: Reimbursement Assessment of CGM – Timeline
Statutory sickness funds apply for an appraisal of CGM
Application is agreed on by G-BA
G-BA commission IQWiG to assess CGM
IQWiG publishes preliminary report plan
Scientific hearing on report plan
Final report plan published (with comments)
IQWiG publishes preliminary report
Scientific hearing on preliminary report
Final report to be sent to G-BA
Expected decision on CGM
“2015 or 2016”
- In light of the slow reimbursement process for CGM, Dr. Sauerland informed us that a new law is under preparation that will speed up the assessment process for “all invasive high-risk devices.” Notable for us, he remarked, “Don’t ask me what high-risk means, though this could involve the artificial pancreas.” The law has passed Germany’s Chamber of States and is presently under review with the Federal Joint Committee. A decision is expected in the next three years. At this point, the implications are unclear, and we will stay tuned for more details as an expedited review process would represent a huge win for patients.
-- by Varun Iyengar, Adam Brown, and Kelly Close